9-Fluorenylmethyloxycarbonyl/ tbutyl-based convergent protein synthesis.

PubMed

Barlos, K; Gatos, D

1999-01-01

Besides linear solid phase peptide synthesis, segment condensation in solution and chemical ligation, convergent peptide synthesis (CPS) was developed in order to enable the efficient preparation of complex peptides and small proteins. According to this synthetic strategy, solid phase synthesized and suitably protected peptide fragments corresponding to the entire peptide/protein-sequence are condensed on a solid support or in solution, to the target protein. This review summarizes CPS performed utilizing the mild 9-fluorenylmethyloxycarbonyl/tbutyloxycarbonyl-based protecting scheme for the amino acids. Copyright 1999 John Wiley & Sons, Inc.

Discovery, Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide, a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria.

PubMed

Gunasekera, Sarath P; Li, Yang; Ratnayake, Ranjala; Luo, Danmeng; Lo, Jeannette; Reibenspies, Joseph H; Xu, Zhengshuang; Clare-Salzler, Michael J; Ye, Tao; Paul, Valerie J; Luesch, Hendrik

2016-06-06

A new dimeric macrolide xylopyranoside, cocosolide (1), was isolated from the marine cyanobacterium preliminarily identified as Symploca sp. from Guam. The structure was determined by a combination of NMR spectroscopy, HRMS, X-ray diffraction studies and Mosher's analysis of the base hydrolysis product. Its carbon skeleton closely resembles that of clavosolides A-D isolated from the sponge Myriastra clavosa, for which no bioactivity is known. We performed the first total synthesis of cocosolide (1) along with its [α,α]-anomer (26) and macrocyclic core (28), thus leading to the confirmation of the structure of natural 1. The convergent synthesis featured Wadsworth-Emmons cyclopropanation, Sakurai annulation, Yamaguchi macrocyclization/dimerization reaction, α-selective glycosidation and β-selective glycosidation. Compounds 1 and 26 potently inhibited IL-2 production in both T-cell receptor dependent and independent manners. Full activity requires the presence of the sugar moiety as well as the intact dimeric structure. Cocosolide also suppressed the proliferation of anti-CD3-stimulated T-cells in a dose-dependent manner. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective synthesis of tatanans A-C and reinvestigation of their glucokinase-activating properties

NASA Astrophysics Data System (ADS)

Xiao, Qing; Jackson, Jeffrey J.; Basak, Ashok; Bowler, Joseph M.; Miller, Brian G.; Zakarian, Armen

2013-05-01

The tatanans are members of a novel class of complex sesquilignan natural products recently isolated from the rhizomes of Acorus tatarinowii Schott plants. Tatanans A, B and C have previously been reported to have potent glucokinase-activating properties that exceed the in vitro activity of known synthetic antidiabetic agents. Here, using a series of sequential [3,3]-sigmatropic rearrangements, we report the total synthesis of tatanan A in 13 steps and 13% overall yield. We also complete a concise enantioselective total synthesis of more complex, atropisomeric tatanans B and C via a distinct convergent strategy based on a palladium-catalysed diastereotopic aromatic group differentiation (12 steps, 4% and 8% overall yield, respectively). A plausible biosynthetic relationship between acyclic tatanan A and spirocyclic tatanans B and C is proposed and probed experimentally. With sufficient quantities of the natural products in hand, we undertake a detailed functional characterization of the biological activities of tatanans A-C. Contrary to previous reports, our assays utilizing pure recombinant human enzyme demonstrate that tatanans do not function as allosteric activators of glucokinase.

Studies toward brevisulcenal F via convergent strategies for marine ladder polyether synthesis.

PubMed

Katcher, Matthew; Jamison, Timothy F

2018-03-15

Shortly after the initial isolation of marine ladder polyether natural products, biomimetic epoxide-opening cascade reactions were proposed as an efficient strategy for the synthesis of these compounds. However, difficulties in assembling the cascade precursors have limited the realization of these cascades. In this report, we describe strategies that provide convergent access to cascade precursors via regioselective allylation and efficient fragment coupling. We then investigate epoxide-opening cascades promoted by strong bases for the formation of fused tetrahydropyrans. These strategies are evaluated in the context of the synthesis of rings CDEFG of brevisulcenal F.

Exploring the feasibility of theory synthesis: A worked example in the field of health related risk-taking

PubMed Central

Pound, Pandora; Campbell, Rona

2015-01-01

The idea of synthesising theory is receiving attention within public health as part of a drive to design theoretically informed interventions. Theory synthesis is not a new idea, however, having been debated by sociologists for several decades. We consider the various methodological approaches to theory synthesis and test the feasibility of one such approach by synthesising a small number of sociological theories relevant to health related risk-taking. The synthesis consisted of three stages: (i) synthesis preparation, wherein parts of relevant theories were extracted and summarised; (ii) synthesis which involved comparing theories for points of convergence and divergence and bringing together those points that converge; and (iii) synthesis refinement whereby the synthesis was interrogated for further theoretical insights. Our synthesis suggests that serious and sustained risk-taking is associated with social isolation, liminality and a person's position in relation to the dominant social group. We reflect upon the methodological and philosophical issues raised by the practice of theory synthesis, concluding that it has the potential to reinvigorate theory and make it more robust and accessible for practical application. PMID:25461862

Approaches to the synthesis of (+/-)-strychnine via the cobalt-mediated [2 + 2 + 2] cycloaddition: rapid assembly of a classic framework.

PubMed

Eichberg, M J; Dorta, R L; Grotjahn, D B; Lamottke, K; Schmidt, M; Vollhardt, K P

2001-09-26

Five synthetic approaches to racemic strychnine (1), with the cobalt-mediated [2 + 2 + 2] cycloaddition of alkynes to indoles as the key step, are described. These include the generation and attempted cyclization of macrocycle 8 and the synthesis of dihydrocarbazoles 15, 22, and 26 and their elaboration to pentacyclic structures via a conjugate addition, dipolar cycloaddition, and propellane-to-spirofused skeletal rearrangement, respectively. Finally, the successful total synthesis of 1 is discussed. The development of a short, highly convergent route (14 steps in the longest linear sequence) is highlighted by the cyclization of enynoylindole 40 with acetylene and the formal intramolecular 1,8-conjugate addition of amine 49 to form pentacycle 50. Numerous attempts toward the formation of the piperidine ring of 1 from vinyl iodide 56 were made and its successful formation via palladium-, nickel-, and radical-mediated processes is described.

Studies Toward the Total Synthesis of Eletefine

NASA Astrophysics Data System (ADS)

Rugg, Kyle William

Eletefine is a natural product of the stephaoxocane family of alkaloids. It possesses an isoquinoline moiety functionalized with three methoxy groups forming an electron rich aromatic system. Eletefine also possesses a ten-membered ring with a novel bridged vinyl ether functionality, and a remote chiral alcohol, making it a conspicuous and desirable target for the synthetic organic chemist. The plant from which eletefine was first isolated (Cissampelos glaberrima ) has been used in traditional medicine for the relief of symptoms from urinary tract infections and asthma. The proposed synthesis of eletefine is a convergent route which features a Sonogashira coupling and a novel alkyne hydration. Herein, methods towards the synthesis of the model system des-hydroxyeletefine are described, in particular attempts towards formation of the AB ring system of des-hydroxyeletefine, as well as C8-C9 bond formation methodology via acylation and Sonogashira coupling.

Preparation of macrocycles with high carbon content: Toward the synthesis of endohedral metal fullerene complexes

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

Parker, T.C.; Rubin, Y.

1995-12-31

This research is focused on the synthesis of macrocycles with high carbon content for the purpose of total synthesis of fullerenes or fullerene-like structures with the ultimate goal of obtaining endohedral metal complexes of fullerene C{sub 60}. Toward this goal, the authors have utilized organometallic chemistry to synthesize novel cyclophanes such as 1 which are constituted primarily of acetylenic units. The authors believe such macrocycles may be C{sub 60} precursors since studies have shown that acetylenic macrocycles form fullerenes in the gas phase. The authors have synthesized macrocycle 1 using a highly convergent route from commercially available starting materials. Themore » macrocycle 1 is produced from copper (I) catalyzed coupling of 2 which is obtained in turn by the coupling of the copper acetylide 3 with 4. The suitability of macrocycles such as 1 for fullerene precursors is currently under investigation.« less

Chemoenzymatic convergent synthesis of 2'-O,4'-C-methyleneribonucleosides.

PubMed

Sharma, Vivek K; Kumar, Manish; Olsen, Carl E; Prasad, Ashok K

2014-07-03

Novozyme-435-catalyzed efficient regioselective acetylation of one of the two diastereotopic hydroxymethyl functions in 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-d-ribofuranose has been achieved. The enzymatic methodology has been successfully utilized for convergent synthesis of bicyclic nucleosides (LNA monomers) T, U, A, and C. Further, it has been demonstrated that Novozyme-435 can be used for 10 cycles of the acylation reaction without losing selectivity and efficiency.

Convergent Synthesis of N-Linked Glycopeptides via Aminolysis of ω-Asp p-Nitrophenyl Thioesters in Solution.

PubMed

Du, Jing-Jing; Gao, Xiao-Fei; Xin, Ling-Ming; Lei, Ze; Liu, Zheng; Guo, Jun

2016-10-07

An efficient N-linked glycosylation reaction between glycosylamines and p-nitrophenyl thioester peptides has been developed. The reaction conditions are mild and compatible with the C-terminal free carboxylic acid group and the unprotected N-linked sialyloligosaccharide. By means of this convergent strategy, a versatile N-glycopeptide fragment containing an N-terminal Thz and a C-terminal thioester was readily prepared, which is available for the synthesis of long glycopeptides and glycoproteins using the protocol of native chemical ligation.

Development of a strategy for the total chemical synthesis of an allergenic protein: the peach LTP Pru p 3.

PubMed

Buhler, Sofie; Akkerdaas, Jaap H; A Pertinhez, Thelma; Van Ree, Ronald; Dossena, Arnaldo; Sforza, Stefano; Tedeschi, Tullia

2017-04-01

The possibility to obtain allergenic proteins by means of total chemical synthesis would be a big step forward in the development of cures to food allergy and in the study of the mechanism of allergic reactions, because this would allow to achieve control at the molecular level over the structure of the product and to study its relationship with the allergenic activity in fine details. This is instead not possible by using allergens produced by extraction from natural sources or by recombinant DNA techniques. In this work, we aimed to test for the first time the feasibility of the total chemical synthesis of an allergenic protein. Pru p 3, the most studied member of the family of lipid transfer proteins, relevant plant food pan-allergens, was used as model target. Strategies for the convergent assembly of the target protein, starting from five peptide fragments to be bound by means of either native chemical ligation or peptide hydrazide ligation, followed by desulfurization, to achieve ligations at alanine, were developed and tested. All the reaction conditions were set up and optimized. Two large peptides covering the two halves of the protein sequence were synthesized and structurally characterized by means of circular dichroism, and their immunogenicity was proved by means of immunoblot, using antibodies against Pru p 3, and immunoCAP inhibition tests. Finally, the five peptides were bound together to produce the whole protein stretch. The obtained results demonstrate the feasibility of total chemical synthesis as a new way to obtain pure allergens. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Simplified Application of Material Efficiency Green Metrics to Synthesis Plans: Pedagogical Case Studies Selected from "Organic Syntheses"

ERIC Educational Resources Information Center

Andraos, John

2015-01-01

This paper presents a simplified approach for the application of material efficiency metrics to linear and convergent synthesis plans encountered in organic synthesis courses. Computations are facilitated and automated using intuitively designed Microsoft Excel spreadsheets without invoking abstract mathematical formulas. The merits of this…

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

PubMed

Ye, Chen-Xi; Melcamu, Yared Yohannes; Li, Heng-Hui; Cheng, Jiang-Tao; Zhang, Tian-Tian; Ruan, Yuan-Ping; Zheng, Xiao; Lu, Xin; Huang, Pei-Qiang

2018-01-29

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

Convergence Theory for Partial Images and Revision of the Definition of Total Images.

ERIC Educational Resources Information Center

Findeisen, Peter

1979-01-01

Guttman's assumption underlying his definition of "total images" is rejected. Partial images are not generally convergent everywhere. Even divergence everywhere is shown to be possible. The convergence type always found on partial images is convergence in quadratic mean; hence, total images are redefined as quadratic mean-limits.…

Solid-phase synthesis of a nucleopeptide from the linking site of adenovirus-2 nucleoprotein, -Ser(p5'CATCAT)-Gly-Asp-. Convergent versus stepwise strategy.

PubMed Central

Robles, J; Pedroso, E; Grandas, A

1995-01-01

The synthesis of a nucleopeptide with the sequence -Ser(p5'CATCAT)-Gly-Asp- has been undertaken by either convergent or stepwise solid-phase strategies, both of which use base-labile permanent protecting groups. The coupling of phosphitylated protected peptides onto oligonucleotide-resins did not afford the desired nucleopeptide, which was nevertheless obtained after oligonucleotide elongation at the hydroxyl group of the resin-bound peptide and deprotection under mild basic conditions. A preliminary study on the stability of different nucleopeptides to bases is also reported. PMID:7479079

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.

Metal-Organic Polyhedral Core as a Versatile Scaffold for Divergent and Convergent Star Polymer Synthesis.

PubMed

Hosono, Nobuhiko; Gochomori, Mika; Matsuda, Ryotaro; Sato, Hiroshi; Kitagawa, Susumu

2016-05-25

We herein report the divergent and convergent synthesis of coordination star polymers (CSP) by using metal-organic polyhedrons (MOPs) as a multifunctional core. For the divergent route, copper-based great rhombicuboctahedral MOPs decorated with dithiobenzoate or trithioester chain transfer groups at the periphery were designed. Subsequent reversible addition-fragmentation chain transfer (RAFT) polymerization of monomers mediated by the MOPs gave star polymers, in which 24 polymeric arms were grafted from the MOP core. On the other hand, the convergent route provided identical CSP architectures by simple mixing of a macroligand and copper ions. Isophthalic acid-terminated polymers (so-called macroligands) immediately formed the corresponding CSPs through a coordination reaction with copper(II) ions. This convergent route enabled us to obtain miktoarm CSPs with tunable chain compositions through ligand mixing alone. This powerful method allows instant access to a wide variety of multicomponent star polymers that conventionally have required highly skilled and multistep syntheses. MOP-core CSPs are a new class of star polymer that can offer a design strategy for highly processable porous soft materials by using coordination nanocages as a building component.

Neural-genetic synthesis for state-space controllers based on linear quadratic regulator design for eigenstructure assignment.

PubMed

da Fonseca Neto, João Viana; Abreu, Ivanildo Silva; da Silva, Fábio Nogueira

2010-04-01

Toward the synthesis of state-space controllers, a neural-genetic model based on the linear quadratic regulator design for the eigenstructure assignment of multivariable dynamic systems is presented. The neural-genetic model represents a fusion of a genetic algorithm and a recurrent neural network (RNN) to perform the selection of the weighting matrices and the algebraic Riccati equation solution, respectively. A fourth-order electric circuit model is used to evaluate the convergence of the computational intelligence paradigms and the control design method performance. The genetic search convergence evaluation is performed in terms of the fitness function statistics and the RNN convergence, which is evaluated by landscapes of the energy and norm, as a function of the parameter deviations. The control problem solution is evaluated in the time and frequency domains by the impulse response, singular values, and modal analysis.

Double [3 + 2]-dimerisation cascade synthesis of bis(triazolyl)bisphosphanes, a new scaffold for bidentate bisphosphanes.

PubMed

Laborde, Coralie; Wei, Muh-Mei; van der Lee, Arie; Deydier, Eric; Daran, Jean-Claude; Volle, Jean-Noël; Poli, Rinaldo; Pirat, Jean-Luc; Manoury, Eric; Virieux, David

2015-07-28

A highly convergent synthesis of bis(triazolylphosphane oxides) was developed by a tandem copper-mediated Huisgen reaction-oxidative coupling. The phosphane oxides were reduced by trichlorosilane and the coordination of the resulting bisphosphanes was studied with various transition metals.

Finding the K best synthesis plans.

PubMed

Fagerberg, Rolf; Flamm, Christoph; Kianian, Rojin; Merkle, Daniel; Stadler, Peter F

2018-04-05

In synthesis planning, the goal is to synthesize a target molecule from available starting materials, possibly optimizing costs such as price or environmental impact of the process. Current algorithmic approaches to synthesis planning are usually based on selecting a bond set and finding a single good plan among those induced by it. We demonstrate that synthesis planning can be phrased as a combinatorial optimization problem on hypergraphs by modeling individual synthesis plans as directed hyperpaths embedded in a hypergraph of reactions (HoR) representing the chemistry of interest. As a consequence, a polynomial time algorithm to find the K shortest hyperpaths can be used to compute the K best synthesis plans for a given target molecule. Having K good plans to choose from has many benefits: it makes the synthesis planning process much more robust when in later stages adding further chemical detail, it allows one to combine several notions of cost, and it provides a way to deal with imprecise yield estimates. A bond set gives rise to a HoR in a natural way. However, our modeling is not restricted to bond set based approaches-any set of known reactions and starting materials can be used to define a HoR. We also discuss classical quality measures for synthesis plans, such as overall yield and convergency, and demonstrate that convergency has a built-in inconsistency which could render its use in synthesis planning questionable. Decalin is used as an illustrative example of the use and implications of our results.

Convergent Synthesis and Structural Confirmation of Phellodonin and Sarcodonin ε

PubMed Central

Usui, Ippei; Lin, David W.; Masuda, Takeshi

2013-01-01

The first synthesis of members of the sarcodonin family, phellodonin and sarcodonin ε, is reported herein. This verifies that the unprecedented and seemingly unstable N,N-dioxide-containing benzodioxazine framework can be constructed in the laboratory, and lends further support to the proposed structures. The key step in the synthesis involves a biomimetic hetero-Diels–Alder reaction between a pyrazine N-oxide and an ortho-quinone. PMID:23577748

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.

Approaches to N-Methylwelwitindolinone C Isothiocyanate: Facile Synthesis of the Tetracyclic Core

PubMed Central

Heidebrecht, Richard W.; Gulledge, Brian; Martin, Stephen F.

2010-01-01

The synthesis of a functionalized, tetracyclic core of N-methylwelwitindolinone C isothiocyanate is reported. The approach features a convergent coupling between an indole iminium ion and a highly functionalized vinylogous silyl ketene acetal followed by an intramolecular palladium-catalyzed cyclization that proceeds via an enolate arylation. PMID:20446675

Measurement of total occlusal convergence of 3 different tooth preparations in 4 different planes by dental students.

PubMed

Yoon, Stephan S; Cheong, Chan; Preisser, John; Jun, Sangho; Chang, Brian M; Wright, Robert F

2014-08-01

Total occlusal convergence of crown preparation is an important didactic and clinical concept in dental education. The purpose of this study was to compare the discrepancy between the total occlusal convergence of dental students' typodont crown preparations and the ideal range (4 to 10 degrees) in 3 different regions of the mouth and in 4 different planes of the teeth. The dental students of the Class of 2012 at Harvard School of Dental Medicine were asked to prepare typodont teeth for crowns on 3 different teeth, the maxillary left central incisor (ceramic), mandibular left first molar (complete metal), and mandibular left first premolar (metal ceramic), during their third year preclinical summative examination and the Comprehensive Clinical Examination in their fourth year. Eighteen students prepared 3 teeth in their third and fourth years, whereas 19 students participated only in their fourth year, for a total of 55 sets of 3 teeth. By using custom fit die bases to reproduce the position, a novel procedure of measuring each tooth was accomplished in 4 different planes: the faciolingual, mesiodistal, mesiofacial-distolingual, and mesiolingual-distofacial. The total occlusal convergence of each image was measured with a computer screen protractor. The gingival 2 mm of the axial wall was used to determine the taper of each wall. Linear mixed model analysis was used to estimate and compare the total occlusal convergences of different teeth and planes (α=.05). Bonferroni corrections were used to adjust for post hoc multiple comparisons. The mean total occlusal convergence varied by tooth and plane (2-way interaction; P<.001). For the first molar, dental students excessively tapered in all 4 planes; the model-predicted 99% CIs for the total occlusal convergence were as follows: faciolingual (12.7, 19.4), mesiodistal (14.0, 19.3), mesiofacial-distolingual (13,4, 19.4), and mesiolingual-distofacial (13.7, 19.1). For the central incisor, 99% CIs for the total occlusal convergence were (15.9, 24.4) for the faciolingual measurement, providing strong evidence of excessive tapering, and (4.1, 8.0) for the mesiodistal measurement, which was within the ideal total occlusal convergence range. The mesiofacial-distolingual and mesiolingual-distofacial planes in the central incisor and all 4 planes in the first premolar had mean total occlusal convergences that exceeded 10 degrees; however, excessive tapering could not be statistically established, because their CIs included values within the ideal range. The present study found significant evidence of excessive tapering in a study comparing the total occlusal convergence values of crown preparations with those of the ideal preparation for 3 different teeth in 4 different planes. The total occlusal convergence for the molar preparations had the highest mean values. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides

PubMed Central

Roberts, Andrew G.; Johnston, Eric V.; Shieh, Jae-Hung; Sondey, Joseph P.; Hendrickson, Ronald C.; Moore, Malcolm A. S.; Danishefsky, Samuel J.

2015-01-01

Human granulocyte colony-stimulating factor (G-CSF) is an endogenous glycoprotein involved in hematopoiesis. Natively glycosylated and nonglycosylated recombinant forms, lenograstim and filgrastim, respectively, are used clinically to manage neutropenia in patients undergoing chemotherapeutic treatment. Despite their comparable therapeutic potential, the purpose of O-linked glycosylation at Thr133 remains a subject of controversy. In light of this, we have developed a synthetic platform to prepare G-CSF aglycone with the goal of enabling access to native and designed glycoforms with site-selectivity and glycan homogeneity. To address the synthesis of a relatively large, aggregation-prone sequence, we advanced an isonitrile-mediated ligation method. The chemoselective activation and coupling of C-terminal peptidyl Gly thioacids with the N-terminus of an unprotected peptide provide ligated peptides directly in a manner complementary to that with conventional native chemical ligation–desulfurization strategies. Herein, we describe the details and application of this method as it enabled the convergent total synthesis of G-CSF aglycone. PMID:26401918

Total synthesis of marinomycin A using salicylate as a molecular switch to mediate dimerization

NASA Astrophysics Data System (ADS)

Evans, P. Andrew; Huang, Mu-Hua; Lawler, Michael J.; Maroto, Sergio

2012-08-01

Antibiotics play a significant role in human health because of their ability to treat life-threatening bacterial infections. The growing problems with antibiotic resistance have made the development of new antibiotics a World Health Organization priority. Marinomycin A is a member of a new class of bis-salicylate-containing polyene macrodiolides, which have potent antibiotic activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Herein, we describe a triply convergent synthesis of this agent using the salicylate as a novel molecular switch for the chemoselective construction of the macrodiolide. This strategy raises new questions regarding the biosynthetic role of the salicylate and its potential impact on the mechanism of action of these types of agents. For instance, in contrast to penicillin, which enhances the electrophilicity of the cyclic amide through ring strain, salicylates reduce the electrophilicity of the aryl ester through an intramolecular resonance-assisted hydrogen bond to provide an amide surrogate.

Convergent synthesis of multiporphyrin light-harvesting rods

DOEpatents

Lindsey, Jonathan S.; Loewe, Robert S.

2003-08-05

The present invention provides a convergent method for the synthesis of light harvesting rods. The rods are oligomers of the formula A.sup.1 (A.sup.b+1).sub.b, wherein b is at least 1, A.sup.1 through A.sup.b+1 are covalently coupled rod segments, and each rod segment A.sup.1 through A.sup.1+b comprises a compound of the formula X.sup.1 (X.sup.m+1).sub.m wherein m is at least 1 and X.sup.1 through X.sup.m+1 are covalently coupled porphyrinic macrocycles. Light harvesting arrays and solar cells containing such light harvesting rods are also described, along with intermediates useful in such methods and rods produced by such methods.

Total Synthesis of Dolatrienoic Acid: A Subunit of Dolastatin 14.

PubMed

Mouné, Sylvie; Niel, Gilles; Busquet, Magali; Eggleston, Ian; Jouin, Patrick

1997-05-16

The (7R,15R)- and (7S,15R)-diastereomers of dolatrienoic acid were synthesized using a convergent strategy. Fragment C5-C9 was obtained through enantiodifferentiation of racemic pentane-1,3,5-triol as the key step, fixing the chirality at C7 of fragments 4 and ent-4. The chirality at C15 of the fragment C10-C16 was introduced from L-glutamic acid. Coupling of these two fragments led to the aldehydes (7R,15R)- and (7S,15R)-2 which were homologated by Horner-Wadsworth-Emmons condensation to give (7R,15R)- and (7S,15R)-dolatrienoic acids.

Quaternary tectonic evolution of the Pamir-Tian Shan convergence zone, Northwest China

NASA Astrophysics Data System (ADS)

Thompson Jobe, Jessica Ann; Li, Tao; Chen, Jie; Burbank, Douglas W.; Bufe, Aaron

2017-12-01

The Pamir-Tian Shan collision zone in the western Tarim Basin, northwest China, formed from rapid and ongoing convergence in response to the Indo-Eurasian collision. The arid landscape preserves suites of fluvial terraces crossing structures active since the late Neogene that create fault and fold scarps recording Quaternary deformation. Using geologic and geomorphic mapping, differential GPS surveys of deformed terraces, and optically stimulated luminescence dating, we create a synthesis of the active structures that delineate the timing, rate, and migration of Quaternary deformation during ongoing convergence. New deformation rates on eight faults and folds, when combined with previous studies, highlight the spatial and temporal patterns of deformation within the Pamir-Tian Shan convergence zone during the Quaternary. Terraces spanning 130 to 8 ka record deformation rates between 0.1 and 5.6 mm/yr on individual structures. In the westernmost Tarim Basin, where the Pamir and Tian Shan are already juxtaposed, the fastest rates occur on actively deforming structures at the interface of the Pamir-Tian Shan orogens. Farther east, as the separation between the Pamir-Tian Shan orogens increases, the deformation has not been concentrated on a single structure, but rather has been concurrently distributed across a zone of faults and folds in the Kashi-Atushi fold-and-thrust belt and along the NE Pamir margin, where shortening rates vary on individual structures during the Quaternary. Although numerous structures accommodate the shortening and the locus of deformation shifts during the Quaternary, the total shortening across the western Tarim Basin has remained steady and approximately matches the current geodetic rate of 6-9 mm/yr.

Conditional silencing of the Escherichia coli pykF gene results from artificial convergent transcription protected from Rho-dependent termination.

PubMed

Krylov, Alexander A; Airich, Larisa G; Kiseleva, Evgeniya M; Minaeva, Natalia I; Biryukova, Irina V; Mashko, Sergey V

2010-01-01

PykF is one of two pyruvate kinases in Escherichia coli K-12. lambdaP(L) was convergently integrated into the chromosome of the MG1655 strain, downstream of pykF, face-to-face with its native promoter. In the presence of lambdacIts857, efficient pykF ts-silencing was achieved when the 5'-terminus of the P(L)-originated antisense RNA (asRNA), consisting of the rrnG-AT sequence, converted elongation complexes of RNA polymerase to a form resistant to Rho-dependent transcription termination. pykF silencing was detected by the following features: (a) impaired growth of the strain when pykA was also disrupted and when using ribose as a non-phosphotransferase system-transporting carbon source; (b) a pattern of reduced synthesis of the full-sized pykF mRNA, mediated by reverse transcription PCR, and (c) a significant decrease in PykF activity. The advantages of anti-terminated convergent transcription were clearly manifested in the strains where the rho_a-terminator was inserted specifically to interrupt asRNA synthesis. Most likely, the target gene was silenced by transcriptional interference due to collisions between converging RNA polymerases, although, strictly, the role of cis-asRNA effects could not be excluded. While details of the mechanisms have yet to be determined, anti-terminated convergent transcription is a promising new technique for silencing other target genes. Copyright 2010 S. Karger AG, Basel.

Convergent transcription in the butyrolactone regulon in Streptomyces coelicolor confers a bistable genetic switch for antibiotic biosynthesis.

PubMed

Chatterjee, Anushree; Drews, Laurie; Mehra, Sarika; Takano, Eriko; Kaznessis, Yiannis N; Hu, Wei-Shou

2011-01-01

cis-encoded antisense RNAs (cis asRNA) have been reported to participate in gene expression regulation in both eukaryotic and prokaryotic organisms. Its presence in Streptomyces coelicolor has also been reported recently; however, its role has yet to be fully investigated. Using mathematical modeling we explore the role of cis asRNA produced as a result of convergent transcription in scbA-scbR genetic switch. scbA and scbR gene pair, encoding repressor-amplifier proteins respectively, mediates the synthesis of a signaling molecule, the γ-butyrolactone SCB1 and controls the onset of antibiotic production. Our model considers that transcriptional interference caused by convergent transcription of two opposing RNA polymerases results in fatal collision and transcriptional termination, which suppresses transcription efficiency. Additionally, convergent transcription causes sense and antisense interactions between complementary sequences from opposing strands, rendering the full length transcript inaccessible for translation. We evaluated the role of transcriptional interference and the antisense effect conferred by convergent transcription on the behavior of scbA-scbR system. Stability analysis showed that while transcriptional interference affects the system, it is asRNA that confers scbA-scbR system the characteristics of a bistable switch in response to the signaling molecule SCB1. With its critical role of regulating the onset of antibiotic synthesis the bistable behavior offers this two gene system the needed robustness to be a genetic switch. The convergent two gene system with potential of transcriptional interference is a frequent feature in various genomes. The possibility of asRNA regulation in other such gene-pairs is yet to be examined.

Optimization of removal function in computer controlled optical surfacing

NASA Astrophysics Data System (ADS)

Chen, Xi; Guo, Peiji; Ren, Jianfeng

2010-10-01

The technical principle of computer controlled optical surfacing (CCOS) and the common method of optimizing removal function that is used in CCOS are introduced in this paper. A new optimizing method time-sharing synthesis of removal function is proposed to solve problems of the removal function being far away from Gaussian type and slow approaching of the removal function error that encountered in the mode of planet motion or translation-rotation. Detailed time-sharing synthesis of using six removal functions is discussed. For a given region on the workpiece, six positions are selected as the centers of the removal function; polishing tool controlled by the executive system of CCOS revolves around each centre to complete a cycle in proper order. The overall removal function obtained by the time-sharing process is the ratio of total material removal in six cycles to time duration of the six cycles, which depends on the arrangement and distribution of the six removal functions. Simulations on the synthesized overall removal functions under two different modes of motion, i.e., planet motion and translation-rotation are performed from which the optimized combination of tool parameters and distribution of time-sharing synthesis removal functions are obtained. The evaluation function when optimizing is determined by an approaching factor which is defined as the ratio of the material removal within the area of half of the polishing tool coverage from the polishing center to the total material removal within the full polishing tool coverage area. After optimization, it is found that the optimized removal function obtained by time-sharing synthesis is closer to the ideal Gaussian type removal function than those by the traditional methods. The time-sharing synthesis method of the removal function provides an efficient way to increase the convergence speed of the surface error in CCOS for the fabrication of aspheric optical surfaces, and to reduce the intermediate- and high-frequency error.

Total chemical synthesis and biological activities of glycosylated and non-glycosylated forms of the chemokines CCL1 and Ser-CCL1.

PubMed

Okamoto, Ryo; Mandal, Kalyaneswar; Ling, Morris; Luster, Andrew D; Kajihara, Yasuhiro; Kent, Stephen B H

2014-05-12

CCL1 is a naturally glycosylated chemokine protein that is secreted by activated T-cells and acts as a chemoattractant for monocytes. Originally, CCL1 was identified as a 73 amino acid protein having one N-glycosylation site, and a variant 74 residue non-glycosylated form, Ser-CCL1, has also been described. There are no systematic studies of the effect of glycosylation on the biological activities of either CCL1 or Ser-CCL1. Here we report the total chemical syntheses of both N-glycosylated and non-glycosylated forms of (Ser-)CCL1, by convergent native chemical ligation. We used an N-glycan isolated from hen egg yolk together with the Nbz linker for Fmoc chemistry solid phase synthesis of the glycopeptide-(α) thioester building block. Chemotaxis assays of these glycoproteins and the corresponding non-glycosylated proteins were carried out. The results were correlated with the chemical structures of the (glyco)protein molecules. To the best of our knowledge, these are the first investigations of the effect of glycosylation on the chemotactic activity of the chemokine (Ser-)CCL1 using homogeneous N-glycosylated protein molecules of defined covalent structure. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A note on convergence of solutions of total variation regularized linear inverse problems

NASA Astrophysics Data System (ADS)

Iglesias, José A.; Mercier, Gwenael; Scherzer, Otmar

2018-05-01

In a recent paper by Chambolle et al (2017 Inverse Problems 33 015002) it was proven that if the subgradient of the total variation at the noise free data is not empty, the level-sets of the total variation denoised solutions converge to the level-sets of the noise free data with respect to the Hausdorff distance. The condition on the subgradient corresponds to the source condition introduced by Burger and Osher (2007 Multiscale Model. Simul. 6 365–95), who proved convergence rates results with respect to the Bregman distance under this condition. We generalize the result of Chambolle et al to total variation regularization of general linear inverse problems under such a source condition. As particular applications we present denoising in bounded and unbounded, convex and non convex domains, deblurring and inversion of the circular Radon transform. In all these examples the convergence result applies. Moreover, we illustrate the convergence behavior through numerical examples.

Mechanisms of DNA replication termination.

PubMed

Dewar, James M; Walter, Johannes C

2017-08-01

Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.

Reduction Expansion Synthesis of Chromium and Nickel Metal Coatings

DTIC Science & Technology

2017-06-01

to a supersonic speed [24]–[25]. To prevent undesired combustion, an inert gas is required for because the gas temperature increases to 100–500°C in...take place. The metal is added by mechanical means only. In the sputtering process, an inert gas (e.g., argon) is supplied to a vacuum chamber with...technique that uses metal powder and compressed gas to feed the powder to a converging-diverging nozzle [24], as shown in Figure 5. The converging

Presidential Green Chemistry Challenge: 2005 Greener Synthetic Pathways Award (Merck & Co., Inc.)

EPA Pesticide Factsheets

Presidential Green Chemistry Challenge 2005 award winner, Merck, designed an atom-economical, energy- and water-saving, convergent synthesis for aprepitant, the active ingredient in Emend, a drug for nausea and vomiting.

Peptide o-aminoanilides as crypto-thioesters for protein chemical synthesis.

PubMed

Wang, Jia-Xing; Fang, Ge-Min; He, Yao; Qu, Da-Liang; Yu, Min; Hong, Zhang-Yong; Liu, Lei

2015-02-09

Fully unprotected peptide o-aminoanilides can be efficiently activated by NaNO2 in aqueous solution to furnish peptide thioesters for use in native chemical ligation. This finding enables the convergent synthesis of proteins from readily synthesizable peptide o-aminoanilides as a new type of crypto-thioesters. The practicality of this approach is shown by the synthesis of histone H2B from five peptide segments. Purification or solubilization tags, which are sometimes needed to improve the efficiency of protein chemical synthesis, can be incorporated into the o-aminoanilide moiety, as demonstrated in the preparation of the cyclic protein lactocyclicin Q. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electronic toll collection/electronic screening interoperability pilot project : final report synthesis

DOT National Transportation Integrated Search

2005-12-02

In 1998, ITS America established a Blue Ribbon Panel on electronic commerce to study the convergence of transportation and electronic payment systems. Panel members included senior managers from government, toll agencies, motor carrier industry, and ...

Synthesis, Properties, and Two-Dimensional Adsorption Characteristics of [6]Hexahelicene-7-carboxylic acid.

PubMed

van der Meijden, Maarten W; Balandina, Tatyana; Ivasenko, Oleksandr; De Feyter, Steven; Wurst, Klaus; Kellogg, Richard M

2016-10-04

A convergent synthesis of racemic [6]hexahelicene-7-carboxylic acid by cross-coupling of a bicyclic and a tricyclic component is described. A metal-catalyzed ring-closure is also a fundamental component of the synthetic approach. Scanning tunneling microscopy (STM) measurements of the racemate self-assembled on Au(111) at liquid-solid interface revealed the formation of ordered racemic 2D crystals. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chiral-catalyst-based convergent synthesis of HIV protease inhibitor GRL-06579A.

PubMed

Mihara, Hisashi; Sohtome, Yoshihiro; Matsunaga, Shigeki; Shibasaki, Masakatsu

2008-02-01

Catalytic asymmetric synthesis of GRL-06579A (1), an HIV-1 protease inhibitor effective against multi-protease-inhibitor-resistant viruses, is described. A convergent strategy that utilizes heterobimetallic multifunctional catalysts developed in our group is a key feature of the synthesis. The chirality of the bicyclic tetrahydrofuran unit of 1 was introduced through Al-Li-bis(binaphthoxide) (ALB) catalyst-controlled Michael addition of dimethyl malonate to racemic 4-O-protected cyclopentenone. ALB afforded not only the trans adduct with up to 96% ee from a matched substrate through kinetic resolution, but also the cis adduct with 99% ee through a catalyst-controlled Michael addition to a mismatched substrate. The Michael addition to produce the unusual cis adduct is described in detail. The framework of the bicyclic tetrahydrofuran was constructed by an intramolecular oxy-Michael reaction. The amino alcohol unit was constructed by an La-Li3-tris(binaphthoxide) (LLB)-catalyzed diastereoselective nitroaldol reaction of N-Boc aldehyde (Boc = tert-butoxycarbonyl) derived from L-phenylalanine. LLB promoted the nitroaldol reaction without racemization of the chiral aldehyde to give the nitroaldol adduct in 85% yield and with 93:7 diastereoselectivity and over 99% ee.

Highly convergent synthesis of chiral bicyclophosphinates by domino hydrophosphinylation/Michael/Michael reaction.

PubMed

Fourgeaud, Pierre; Daydé, Bénédicte; Volle, Jean-Noël; Vors, Jean-Pierre; Van der Lee, Arie; Pirat, Jean-Luc; Virieux, David

2011-10-07

Diastereoselective domino reactions of iminoalcohols and allenyl H-phosphinates produce chiral phosphorus bicycles in a regio- and stereoselective fashion. A predictive model for diastereoselection is used for these new chiral phosphinic esters. © 2011 American Chemical Society

Synthesis of 1D Bragg gratings by a layer-aggregation method.

PubMed

Capmany, José; Muriel, Miguel A; Sales, Salvador

2007-08-15

We present what we believe to be a novel method for the synthesis of complex 1D (fiber and waveguide) Bragg gratings, which is based on an impedance reconstruction layer aggregation technique. The main advantage brought by the method is the possibility of synthesizing structures containing defects or discontinuities of the size of the local period, a feature that is not possible with prior reported methods. In addition, this enhanced spatial resolution allows the synthesis of very strong fiber Bragg grating devices providing convergent solutions. The method directly renders the refractive index profile n(z) as it does not rely on the coupled-mode theory.

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides.

PubMed

Benito-Alifonso, David; Jones, Rachel A; Tran, Anh-Tuan; Woodward, Hannah; Smith, Nichola; Galan, M Carmen

2013-01-01

The chemical synthesis of a series of mucin-type oligosaccharide fragments 1-7 containing an α-linked aminopropyl spacer ready for glycoarray attachment is reported. A highly convergent and stereoselective strategy that employs two different orthogonal protected galactosamine building blocks was used to access all of the targets. A tandem deprotection sequence, that did not require chromatography-based purification between steps, was employed to globally unmask all protecting groups and all final targets were isolated in good to excellent yields.

Satisfaction and dissatisfaction in the work of recyclable solid waste segregators: convergent-care research.

PubMed

Coelho, Alexa Pupiara Flores; Beck, Carmem Lúcia Colomé; Silva, Rosângela Marion da; Prestes, Francine Cassol; Camponogara, Silviamar; Peserico, Anahlú

2017-04-01

describe elements that promote satisfaction and dissatisfaction in the work of recyclable solid waste segregators and conduct a nursing action focused on these elements. qualitative research, convergent-care, conducted with members of the cooperative. Data production occurred during 2015 through participation observation, semi-structured interviews, and a convergence group. Analysis comprised the phases Apprehension, Synthesis, Theorization, and Transference. four categories emerged. They showed satisfaction and dissatisfaction related to identification with tasks and work content, material and personal gains obtained from solid waste segregation, prejudice, lack of appreciation, and difficulties in interpersonal relationships. This last item, due to its importance, received a nursing action. the study contributed to the advancement of knowledge and the association of possibilities between the research performance and nursing care for workers.

Synthesis of coupled resonator optical waveguides by cavity aggregation.

PubMed

Muñoz, Pascual; Doménech, José David; Capmany, José

2010-01-18

In this paper, the layer aggregation method is applied to coupled resonator optical waveguides. Starting from the frequency transfer function, the method yields the coupling constants between the resonators. The convergence of the algorithm developed is examined and the related parameters discussed.

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.

Convergent synthesis of proteins by kinetically controlled ligation

DOEpatents

Kent, Stephen; Pentelute, Brad; Bang, Duhee; Johnson, Erik; Durek, Thomas

2010-03-09

The present invention concerns methods and compositions for synthesizing a polypeptide using kinetically controlled reactions involving fragments of the polypeptide for a fully convergent process. In more specific embodiments, a ligation involves reacting a first peptide having a protected cysteyl group at its N-terminal and a phenylthioester at its C-terminal with a second peptide having a cysteine residue at its N-termini and a thioester at its C-termini to form a ligation product. Subsequent reactions may involve deprotecting the cysteyl group of the resulting ligation product and/or converting the thioester into a thiophenylester.

Convergence of Hippocampal Pathophysiology in Syngap+/- and Fmr1-/y Mice.

PubMed

Barnes, Stephanie A; Wijetunge, Lasani S; Jackson, Adam D; Katsanevaki, Danai; Osterweil, Emily K; Komiyama, Noboru H; Grant, Seth G N; Bear, Mark F; Nägerl, U Valentin; Kind, Peter C; Wyllie, David J A

2015-11-11

Previous studies have hypothesized that diverse genetic causes of intellectual disability (ID) and autism spectrum disorders (ASDs) converge on common cellular pathways. Testing this hypothesis requires detailed phenotypic analyses of animal models with genetic mutations that accurately reflect those seen in the human condition (i.e., have structural validity) and which produce phenotypes that mirror ID/ASDs (i.e., have face validity). We show that SynGAP haploinsufficiency, which causes ID with co-occurring ASD in humans, mimics and occludes the synaptic pathophysiology associated with deletion of the Fmr1 gene. Syngap(+/-) and Fmr1(-/y) mice show increases in basal protein synthesis and metabotropic glutamate receptor (mGluR)-dependent long-term depression that, unlike in their wild-type controls, is independent of new protein synthesis. Basal levels of phosphorylated ERK1/2 are also elevated in Syngap(+/-) hippocampal slices. Super-resolution microscopy reveals that Syngap(+/-) and Fmr1(-/y) mice show nanoscale alterations in dendritic spine morphology that predict an increase in biochemical compartmentalization. Finally, increased basal protein synthesis is rescued by negative regulators of the mGlu subtype 5 receptor and the Ras-ERK1/2 pathway, indicating that therapeutic interventions for fragile X syndrome may benefit patients with SYNGAP1 haploinsufficiency. As the genetics of intellectual disability (ID) and autism spectrum disorders (ASDs) are unraveled, a key issue is whether genetically divergent forms of these disorders converge on common biochemical/cellular pathways and hence may be amenable to common therapeutic interventions. This study compares the pathophysiology associated with the loss of fragile X mental retardation protein (FMRP) and haploinsufficiency of synaptic GTPase-activating protein (SynGAP), two prevalent monogenic forms of ID. We show that Syngap(+/-) mice phenocopy Fmr1(-/y) mice in the alterations in mGluR-dependent long-term depression, basal protein synthesis, and dendritic spine morphology. Deficits in basal protein synthesis can be rescued by pharmacological interventions that reduce the mGlu5 receptor-ERK1/2 signaling pathway, which also rescues the same deficit in Fmr1(-/y) mice. Our findings support the hypothesis that phenotypes associated with genetically diverse forms of ID/ASDs result from alterations in common cellular/biochemical pathways. Copyright © 2015 Barnes et al.

Advanced Concurrent-Multiband, Multibeam, Aperture-Synthesis with Intelligent Processing for Urban Operation Sensing

DTIC Science & Technology

2012-04-09

signatures (RSS), in particular, despeckling, superresolution and convergence rate, for a variety of admissible 115 imaging array sensor...attain the superresolution performances in the resulting SSP estimates (3.4), we propose the VA inspired approach [13], [14] to specify the POCS

A microwave assisted intramolecular-furan-Diels-Alder approach to 4-substituted indoles.

PubMed

Petronijevic, Filip; Timmons, Cody; Cuzzupe, Anthony; Wipf, Peter

2009-01-07

The key steps of a versatile new protocol for the convergent synthesis of 3,4-disubstituted indoles are the addition of an alpha-lithiated alkylaminofuran to a carbonyl compound, a microwave-accelerated intramolecular Diels-Alder cycloaddition and an in situ double aromatization reaction.

[Au]/[Ag]-catalysed expedient synthesis of branched heneicosafuranosyl arabinogalactan motif of Mycobacterium tuberculosis cell wall

NASA Astrophysics Data System (ADS)

Thadke, Shivaji A.; Mishra, Bijoyananda; Islam, Maidul; Pasari, Sandip; Manmode, Sujit; Rao, Boddu Venkateswara; Neralkar, Mahesh; Shinde, Ganesh P.; Walke, Gulab; Hotha, Srinivas

2017-01-01

Emergence of multidrug-resistant and extreme-drug-resistant strains of Mycobacterium tuberculosis (MTb) can cause serious socioeconomic burdens. Arabinogalactan present on the cellular envelope of MTb is unique and is required for its survival; access to arabinogalactan is essential for understanding the biosynthetic machinery that assembles it. Isolation from Nature is a herculean task and, as a result, chemical synthesis is the most sought after technique. Here we report a convergent synthesis of branched heneicosafuranosyl arabinogalactan (HAG) of MTb. Key furanosylations are performed using [Au]/[Ag] catalysts. The synthesis of HAG is achieved by the repetitive use of three reactions namely 1,2-trans furanoside synthesis by propargyl 1,2-orthoester donors, unmasking of silyl ether, and conversion of n-pentenyl furanosides into 1,2-orthoesters. Synthesis of HAG is achieved in 47 steps (with an overall yield of 0.09%) of which 21 are installation of furanosidic linkages in a stereoselective manner.

Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor-Associated Carbohydrate Antigen

PubMed Central

Tang, Shouchu; Wang, Qianli

2010-01-01

Monophosphoryl lipid A is a safe and potent immunostimulant and vaccine adjuvant, which is potentially useful for the development of effective carbohydrate-based conjugate vaccines. This paper presented a convergent and efficient synthesis of a monophosphoryl derivative of E. coli lipid A having an alkyne functionality at the reducing end, which is suitable for the coupling with various molecules. The coupling of this derivative to an N-modified analog of tumor-associated antigen GM3 by click chemistry is also presented. PMID:19943286

Weight of evidence evaluation of adverse outcome pathways converging at impaired vitellogenin synthesis leading to reproductive impairment

EPA Science Inventory

Adverse outcome pathways (AOPs) provide a framework that supports greater use of mechanistic data measured at lower levels of biological organization as a basis for regulatory decision-making. However, it is recognized that different types of regulatory applications and decisions...

A microwave assisted intramolecular-furan-Diels–Alder approach to 4-substituted indoles†

PubMed Central

Petronijevic, Filip; Timmons, Cody; Cuzzupe, Anthony; Wipf, Peter

2009-01-01

The key steps of a versatile new protocol for the convergent synthesis of 3,4-disubstituted indoles are the addition of an α-lithiated alkylaminofuran to a carbonyl compound, a microwave-accelerated intramolecular Diels–Alder cycloaddition and an in situ double aromatization reaction. PMID:19082013

The Effect of Molar Axial Wall Height on CAD/CAM Ceramic Crowns With Moderate Occlusal Convergence

DTIC Science & Technology

2006-05-01

CEREC e.max* CAD crowns on preparations with moderate total occlusal convergence (16 degrees). Methods: 60 recently-extracted maxillary third molars ...The Effect of Molar Axial Wall Height on CAD/CAM Ceramic Crowns With Moderate Occlusal Convergence Wyeth L. Hoopes The Effect of Molar Axial Wall... Molar Axial Wall Height on CAD/CAM Ceramic Crowns With Moderate Occlusal Convergence is appropria tely acknowledged and beyond brief excerpts, is with

A Stochastic Total Least Squares Solution of Adaptive Filtering Problem

PubMed Central

Ahmad, Noor Atinah

2014-01-01

An efficient and computationally linear algorithm is derived for total least squares solution of adaptive filtering problem, when both input and output signals are contaminated by noise. The proposed total least mean squares (TLMS) algorithm is designed by recursively computing an optimal solution of adaptive TLS problem by minimizing instantaneous value of weighted cost function. Convergence analysis of the algorithm is given to show the global convergence of the proposed algorithm, provided that the stepsize parameter is appropriately chosen. The TLMS algorithm is computationally simpler than the other TLS algorithms and demonstrates a better performance as compared with the least mean square (LMS) and normalized least mean square (NLMS) algorithms. It provides minimum mean square deviation by exhibiting better convergence in misalignment for unknown system identification under noisy inputs. PMID:24688412

Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway

PubMed Central

Das, Utpal; Scott, David; Ganguly, Archan; Koo, Edward H.; Tang, Yong; Roy, Subhojit

2013-01-01

The convergence of APP (substrate) and BACE-1 (enzyme) is a rate-limiting, obligatory event triggering the amyloidogenic pathway – a key step in Alzheimer’s disease (AD) pathology. However, as both APP/BACE-1 are highly expressed in brain, mechanisms precluding their unabated convergence are unclear. Exploring dynamic localization of APP/BACE-1 in cultured hippocampal neurons, we found that after synthesis via the secretory-pathway, dendritic APP/BACE-1-containing vesicles are largely segregated in physiologic states. While BACE-1 is largely sorted into acidic recycling endosomes, APP is conveyed in Golgi-derived vesicles. However upon activity-induction – a known trigger of the amyloidogenic pathway – APP is routed into BACE-1-positive recycling endosomes via a clathrin-dependent mechanism. A partitioning/convergence of APP/BACE-1 vesicles is also apparent in control/AD brains respectively. Considering BACE-1 is optimally active in an acidic environment, our experiments suggest that neurons have evolved trafficking strategies that normally limit APP/BACE-1 proximity; and also uncover a pathway routing APP into BACE-1-containing organelles – triggering amyloidogenesis. PMID:23931995

Why the short face? Developmental disintegration of the neurocranium drives convergent evolution in neotropical electric fishes.

PubMed

Evans, Kory M; Waltz, Brandon; Tagliacollo, Victor; Chakrabarty, Prosanta; Albert, James S

2017-03-01

Convergent evolution is widely viewed as strong evidence for the influence of natural selection on the origin of phenotypic design. However, the emerging evo-devo synthesis has highlighted other processes that may bias and direct phenotypic evolution in the presence of environmental and genetic variation. Developmental biases on the production of phenotypic variation may channel the evolution of convergent forms by limiting the range of phenotypes produced during ontogeny. Here, we study the evolution and convergence of brachycephalic and dolichocephalic skull shapes among 133 species of Neotropical electric fishes (Gymnotiformes: Teleostei) and identify potential developmental biases on phenotypic evolution. We plot the ontogenetic trajectories of neurocranial phenotypes in 17 species and document developmental modularity between the face and braincase regions of the skull. We recover a significant relationship between developmental covariation and relative skull length and a significant relationship between developmental covariation and ontogenetic disparity. We demonstrate that modularity and integration bias the production of phenotypes along the brachycephalic and dolichocephalic skull axis and contribute to multiple, independent evolutionary transformations to highly brachycephalic and dolichocephalic skull morphologies.

The convergence of health care financing structures: empirical evidence from OECD-countries.

PubMed

Leiter, Andrea M; Theurl, Engelbert

2012-02-01

The convergence/divergence of health care systems between countries is an interesting facet of the health care system research from a macroeconomic perspective. In this paper, we concentrate on an important dimension of every health care system, namely the convergence/divergence of health care financing (HCF). Based on data from 22 OECD countries in the time period 1970-2005, we use the public financing ratio (public financing in % of total HCF) and per capita public HCF as indicators for convergence. By applying different concepts of convergence, we find that HCF is converging. This conclusion also holds when we look at smaller subgroups of countries and shorter time periods. However, we find evidence that countries do not move towards a common mean and that the rate of convergence is decreasing over time.

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.

The relationship between low-level convergence and precipitation in CMIP5 current and future climates

NASA Astrophysics Data System (ADS)

Weller, Evan; Jakob, Christian; Reeder, Michael

2017-04-01

Precipitation is often organized along coherent lines of low-level convergence, which at longer time and space scales form well-known convergence zones over the tropical oceans. Here, an automated, objective method is used to identify instantaneous low-level convergence lines in the current climate of CMIP5 models and compared with reanalysis data results. Identified convergence lines are combined with precipitation to assess the extent to which precipitation around the globe is associated with convergence in the lower troposphere. Differences between the current climate of the models and observations are diagnosed in terms of the frequency and intensity of both precipitation associated with convergence lines and that which is not. Future changes in frequency and intensity of convergence lines, and associated precipitation, are also investigated for their contribution to the simulated future changes in total precipitation.

Convergent synthesis of a trisaccharide as its 2-(trimethylsilyl)ethyl glycoside related to the flavonoid triglycoside from Gymnema sylvestre.

PubMed

Mukhopadhyay, Balaram; Field, Robert A

2006-07-24

The glycone part of the flavonoid triglycoside, kaempferol 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside, has been synthesized in good yield and stereoselectivity using N-iodosuccinimide and HClO4-silica promoted glycosylations of thioglycoside donors.

Divergent and convergent synthesis of GalNAc-conjugated dendrimers using dual orthogonal ligations.

PubMed

Thomas, Baptiste; Pifferi, Carlo; Daskhan, Gour Chand; Fiore, Michele; Berthet, Nathalie; Renaudet, Olivier

2015-12-21

The synthesis of glycodendrimers remains a challenging task. In this paper we propose a protocol based on both oxime ligation (OL) to combine cyclopeptide repeating units as the dendritic core and the copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) to conjugate peripheral α and β propargylated GalNAc. By contrast with the oxime-based iterative protocol reported in our group, our current strategy can be used in both divergent and convergent routes with similar efficiency and the resulting hexadecavalent glycodendrimers can be easily characterized compared to oxime-linked analogues. A series of glycoconjugates displaying four or sixteen copies of both α and β GalNAc have been prepared and their ability to inhibit the adhesion of the soybean agglutinin (SBA) lectin to polymeric-GalNAc immobilized on microtiter plates has been evaluated. As was anticipated, the higher inhibitory effect (IC50 = 0.46 μM) was measured with the structure displaying αGalNAc with the higher valency (compound 13), which demonstrates that the binding properties of these glycoconjugates are strongly dependent on the orientation and distribution of the GalNAc units.

Psychometric properties of the mobility inventory for agoraphobia: convergent, discriminant, and criterion-related validity.

PubMed

Chambless, Dianne L; Sharpless, Brian A; Rodriguez, Dianeth; McCarthy, Kevin S; Milrod, Barbara L; Khalsa, Shabad-Ratan; Barber, Jacques P

2011-12-01

Aims of this study were (a) to summarize the psychometric literature on the Mobility Inventory for Agoraphobia (MIA), (b) to examine the convergent and discriminant validity of the MIA's Avoidance Alone and Avoidance Accompanied rating scales relative to clinical severity ratings of anxiety disorders from the Anxiety Disorders Interview Schedule (ADIS), and (c) to establish a cutoff score indicative of interviewers' diagnosis of agoraphobia for the Avoidance Alone scale. A meta-analytic synthesis of 10 published studies yielded positive evidence for internal consistency and convergent and discriminant validity of the scales. Participants in the present study were 129 people with a diagnosis of panic disorder. Internal consistency was excellent for this sample, α=.95 for AAC and .96 for AAL. When the MIA scales were correlated with interviewer ratings, evidence for convergent and discriminant validity for AAL was strong (convergent r with agoraphobia severity ratings=.63 vs. discriminant rs of .10-.29 for other anxiety disorders) and more modest but still positive for AAC (.54 vs. .01-.37). Receiver operating curve analysis indicated that the optimal operating point for AAL as an indicator of ADIS agoraphobia diagnosis was 1.61, which yielded sensitivity of .87 and specificity of .73. Copyright © 2011. Published by Elsevier Ltd.

Psychometric Properties of the Mobility Inventory for Agoraphobia: Convergent, Discriminant, and Criterion-Related Validity

PubMed Central

Chambless, Dianne L.; Sharpless, Brian A.; Rodriguez, Dianeth; McCarthy, Kevin S.; Milrod, Barbara L.; Khalsa, Shabad-Ratan; Barber, Jacques P.

2012-01-01

Aims of this study were (a) to summarize the psychometric literature on the Mobility Inventory for Agoraphobia (MIA), (b) to examine the convergent and discriminant validity of the MIA’s Avoidance Alone and Avoidance Accompanied rating scales relative to clinical severity ratings of anxiety disorders from the Anxiety Disorders Interview Schedule (ADIS), and (c) to establish a cutoff score indicative of interviewers’ diagnosis of agoraphobia for the Avoidance Alone scale. A meta-analytic synthesis of 10 published studies yielded positive evidence for internal consistency and convergent and discriminant validity of the scales. Participants in the present study were 129 people with a diagnosis of panic disorder. Internal consistency was excellent for this sample, α = .95 for AAC and .96 for AAL. When the MIA scales were correlated with interviewer ratings, evidence for convergent and discriminant validity for AAL was strong (convergent r with agoraphobia severity ratings = .63 vs. discriminant rs of .10-.29 for other anxiety disorders) and more modest but still positive for AAC (.54 vs. .01-.37). Receiver operating curve analysis indicated that the optimal operating point for AAL as an indicator of ADIS agoraphobia diagnosis was 1.61, which yielded sensitivity of .87 and specificity of .73. PMID:22035997

Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133.

PubMed

Maltais, René; Hospital, Audrey; Delhomme, Audrey; Roy, Jenny; Poirier, Donald

2014-04-01

The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. Copyright © 2014 Elsevier Inc. All rights reserved.

Convergent solid-phase and solution approaches in the synthesis of the cysteine-rich Mdm2 RING finger domain.

PubMed

Vasileiou, Zoe; Barlos, Kostas; Gatos, Dimitrios

2009-12-01

The RING finger domain of the Mdm2, located at the C-terminus of the protein, is necessary for regulation of p53, a tumor suppressor protein. The 48-residues long Mdm2 peptide is an important target for studying its interaction with small anticancer drug candidates. For the chemical synthesis of the Mdm2 RING finger domain, the fragment condensation on solid-phase and the fragment condensation in solution were studied. The latter method was performed using either protected or free peptides at the C-terminus as the amino component. Best results were achieved using solution condensation where the N-component was applied with the C-terminal carboxyl group left unprotected. The developed method is well suited for large-scale synthesis of Mdm2 RING finger domain, combining the advantages of both solid-phase and solution synthesis. (c) 2009 European Peptide Society and John Wiley & Sons, Ltd.

Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.

PubMed

Heinz, Christoph; Lutz, J Patrick; Simmons, Eric M; Miller, Michael M; Ewing, William R; Doyle, Abigail G

2018-02-14

This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via α-amino radical formation. Accordingly, application of catalytic conditions to an intramolecular reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.

Blueprinting macromolecular electronics.

PubMed

Palma, Carlos-Andres; Samorì, Paolo

2011-06-01

Recently, by mastering either top-down or bottom-up approaches, tailor-made macromolecular nano-objects with semiconducting properties have been fabricated. These engineered nanostructures for organic electronics are based on conjugated systems predominantly made up of sp²-hybridized carbon, such as graphene nanoribbons. Here, we describe developments in a selection of these nanofabrication techniques, which include graphene carving, stimulus-induced synthesis of conjugated polymers and surface-assisted synthesis. We also assess their potential to reproduce chemically and spatially precise molecular arrangements, that is, molecular blueprints. In a broad context, the engineering of a molecular blueprint represents the fabrication of an integrated all-organic macromolecular electronic circuit. In this Perspective, we suggest chemical routes, as well as convergent on-surface synthesis and microfabrication approaches, for the ultimate goal of bringing the field closer to technology.

Simple Convergences? Piagetian Theory and Its Relationship to the Epistemology of James Mark Baldwin.

ERIC Educational Resources Information Center

Marelich, William D.; And Others

Jean Piaget is credited with such topics as the synthesis of philosophy and the life sciences through a description of progressive stage by stage development, and a genetic epistemology founded on the principle of knowledge through processes of cognitive assimilation and accommodation. In actuality, these themes were originally postulated by James…

The CP molecule labyrinth: a paradigm of how endeavors in total synthesis lead to discoveries and inventions in organic synthesis.

PubMed

Nicolaou, K C; Baran, Phil S

2002-08-02

Imagine an artist carving a sculpture from a marble slab and finding gold nuggets in the process. This thought is not a far-fetched description of the work of a synthetic chemist pursuing the total synthesis of a natural product. At the end of the day, he or she will be judged by the artistry of the final work and the weight of the gold discovered in the process. However, as colorful as this description of total synthesis may be, it does not entirely capture the essence of the endeavor, for there is much more to be told, especially with regard to the contrast of frustrating failures and exhilarating moments of discovery. To fully appreciate the often Herculean nature of the task and the rewards that accompany it, one must sense the details of the enterprise behind the scenes. A more vivid description of total synthesis as a struggle against a tough opponent is perhaps appropriate to dramatize these elements of the experience. In this article we describe one such endeavor of total synthesis which, in addition to reaching the target molecule, resulted in a wealth of new synthetic strategies and technologies for chemical synthesis. The total synthesis of the CP molecules is compared to Theseus' most celebrated athlos (Greek for exploit, accomplishment): the conquest of the dreaded Minotaur, which he accomplished through brilliance, skill, and bravery having traversed the famous labyrinth with the help of Ariadne. This story from Greek mythology comes alive in modern synthetic expeditions toward natural products as exemplified by the total synthesis of the CP molecules which serve as a paradigm for modern total synthesis endeavors, where the objectives are discovery and invention in the broader sense of organic synthesis.

Compressed sensing with gradient total variation for low-dose CBCT reconstruction

NASA Astrophysics Data System (ADS)

Seo, Chang-Woo; Cha, Bo Kyung; Jeon, Seongchae; Huh, Young; Park, Justin C.; Lee, Byeonghun; Baek, Junghee; Kim, Eunyoung

2015-06-01

This paper describes the improvement of convergence speed with gradient total variation (GTV) in compressed sensing (CS) for low-dose cone-beam computed tomography (CBCT) reconstruction. We derive a fast algorithm for the constrained total variation (TV)-based a minimum number of noisy projections. To achieve this task we combine the GTV with a TV-norm regularization term to promote an accelerated sparsity in the X-ray attenuation characteristics of the human body. The GTV is derived from a TV and enforces more efficient computationally and faster in convergence until a desired solution is achieved. The numerical algorithm is simple and derives relatively fast convergence. We apply a gradient projection algorithm that seeks a solution iteratively in the direction of the projected gradient while enforcing a non-negatively of the found solution. In comparison with the Feldkamp, Davis, and Kress (FDK) and conventional TV algorithms, the proposed GTV algorithm showed convergence in ≤18 iterations, whereas the original TV algorithm needs at least 34 iterations in reducing 50% of the projections compared with the FDK algorithm in order to reconstruct the chest phantom images. Future investigation includes improving imaging quality, particularly regarding X-ray cone-beam scatter, and motion artifacts of CBCT reconstruction.

Peptide/protein-polymer conjugates: synthetic strategies and design concepts.

PubMed

Gauthier, Marc A; Klok, Harm-Anton

2008-06-21

This feature article provides a compilation of tools available for preparing well-defined peptide/protein-polymer conjugates, which are defined as hybrid constructs combining (i) a defined number of peptide/protein segments with uniform chain lengths and defined monomer sequences (primary structure) with (ii) a defined number of synthetic polymer chains. The first section describes methods for post-translational, or direct, introduction of chemoselective handles onto natural or synthetic peptides/proteins. Addressed topics include the residue- and/or site-specific modification of peptides/proteins at Arg, Asp, Cys, Gln, Glu, Gly, His, Lys, Met, Phe, Ser, Thr, Trp, Tyr and Val residues and methods for producing peptides/proteins containing non-canonical amino acids by peptide synthesis and protein engineering. In the second section, methods for introducing chemoselective groups onto the side-chain or chain-end of synthetic polymers produced by radical, anionic, cationic, metathesis and ring-opening polymerization are described. The final section discusses convergent and divergent strategies for covalently assembling polymers and peptides/proteins. An overview of the use of chemoselective reactions such as Heck, Sonogashira and Suzuki coupling, Diels-Alder cycloaddition, Click chemistry, Staudinger ligation, Michael's addition, reductive alkylation and oxime/hydrazone chemistry for the convergent synthesis of peptide/protein-polymer conjugates is given. Divergent approaches for preparing peptide/protein-polymer conjugates which are discussed include peptide synthesis from synthetic polymer supports, polymerization from peptide/protein macroinitiators or chain transfer agents and the polymerization of peptide side-chain monomers.

Synthesis, Properties, and Two-Dimensional Adsorption Characteristics of 5-Amino[6]hexahelicene.

PubMed

van der Meijden, Maarten W; Gelens, Edith; Quirós, Natalia Murillo; Fuhr, Javier D; Gayone, J Esteban; Ascolani, Hugo; Wurst, Klaus; Lingenfelder, Magalí; Kellogg, Richard M

2016-01-22

A convergent synthesis of racemic 5-amino[6]hexahelicene is described. Cross-coupling reactions are used to assemble a pentacyclic framework, and a metal-catalyzed ring-closure comprises the final step. The enantiomers were separated by means of chromatography and the absolute configurations were assigned by comparison of the CD spectra with hexahelicene. The t1/2  value for racemization at 210 °C was approximately 1 hour. Scanning tunneling microscopy (STM) measurements were carried out on enantiopure and racemic samples of aminohelicene on Au(111) under ultrahigh vacuum (UHV) conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Divergent Synthesis of Revised Apratoxin E, 30-epi-Apratoxin E, and 30S/30R-Oxoapratoxin E.

PubMed

Mao, Zhuo-Ya; Si, Chang-Mei; Liu, Yi-Wen; Dong, Han-Qing; Wei, Bang-Guo; Lin, Guo-Qiang

2017-10-20

In this report, originally proposed apratoxin E (30S-7), revised apratoxin E (30R-7), and (30S)/(30R)-oxoapratoxin E (30S)-38/(30R)-38 were efficiently prepared by two synthetic methods. The chiral lactone 10, recycled from the degradation of saponin glycosides, was utilized to prepare the key nonpeptide fragment 9. Our alternative convergent assembly strategy was applied to the divergent synthesis of revised apratoxin E and its three analogues. Moreover, ring-closing metathesis (RCM) was for the first time found to be an efficient strategy for the macrocyclization of apratoxins.

Advancement of Bi-Level Integrated System Synthesis (BLISS)

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, Jaroslaw; Emiley, Mark S.; Agte, Jeremy S.; Sandusky, Robert R., Jr.

2000-01-01

Bi-Level Integrated System Synthesis (BLISS) is a method for optimization of an engineering system, e.g., an aerospace vehicle. BLISS consists of optimizations at the subsystem (module) and system levels to divide the overall large optimization task into sets of smaller ones that can be executed concurrently. In the initial version of BLISS that was introduced and documented in previous publications, analysis in the modules was kept at the early conceptual design level. This paper reports on the next step in the BLISS development in which the fidelity of the aerodynamic drag and structural stress and displacement analyses were upgraded while the method's satisfactory convergence rate was retained.

Does healthcare financing converge? Evidence from eight OECD countries.

PubMed

Chen, Wen-Yi

2013-12-01

This study investigated the convergence of healthcare financing across eight OECD countries during 1960-2009 for the first time. The panel stationary test incorporating both shapes of multiple structural breaks (i.e., sharp drifts and smooth transition shifts) and cross-sectional dependence was used to provide reliable evidence of convergence in healthcare financing. Our results suggested that the public share of total healthcare financing in eight OECD countries has exhibited signs of convergence towards that of the US. The convergence of healthcare financing not only reflected a decline in the share of public healthcare financing in these eight OECD countries but also exhibited an upward trend in the share of public healthcare financing in the US over the period of 1960-2009.

Convergence behavior of the random phase approximation renormalized correlation energy

NASA Astrophysics Data System (ADS)

Bates, Jefferson E.; Sensenig, Jonathon; Ruzsinszky, Adrienn

2017-05-01

Based on the random phase approximation (RPA), RPA renormalization [J. E. Bates and F. Furche, J. Chem. Phys. 139, 171103 (2013), 10.1063/1.4827254] is a robust many-body perturbation theory that works for molecules and materials because it does not diverge as the Kohn-Sham gap approaches zero. Additionally, RPA renormalization enables the simultaneous calculation of RPA and beyond-RPA correlation energies since the total correlation energy is the sum of a series of independent contributions. The first-order approximation (RPAr1) yields the dominant beyond-RPA contribution to the correlation energy for a given exchange-correlation kernel, but systematically underestimates the total beyond-RPA correction. For both the homogeneous electron gas model and real systems, we demonstrate numerically that RPA renormalization beyond first order converges monotonically to the infinite-order beyond-RPA correlation energy for several model exchange-correlation kernels and that the rate of convergence is principally determined by the choice of the kernel and spin polarization of the ground state. The monotonic convergence is rationalized from an analysis of the RPA renormalized correlation energy corrections, assuming the exchange-correlation kernel and response functions satisfy some reasonable conditions. For spin-unpolarized atoms, molecules, and bulk solids, we find that RPA renormalization is typically converged to 1 meV error or less by fourth order regardless of the band gap or dimensionality. Most spin-polarized systems converge at a slightly slower rate, with errors on the order of 10 meV at fourth order and typically requiring up to sixth order to reach 1 meV error or less. Slowest to converge, however, open-shell atoms present the most challenging case and require many higher orders to converge.

Multiple Representations-Based Face Sketch-Photo Synthesis.

PubMed

Peng, Chunlei; Gao, Xinbo; Wang, Nannan; Tao, Dacheng; Li, Xuelong; Li, Jie

2016-11-01

Face sketch-photo synthesis plays an important role in law enforcement and digital entertainment. Most of the existing methods only use pixel intensities as the feature. Since face images can be described using features from multiple aspects, this paper presents a novel multiple representations-based face sketch-photo-synthesis method that adaptively combines multiple representations to represent an image patch. In particular, it combines multiple features from face images processed using multiple filters and deploys Markov networks to exploit the interacting relationships between the neighboring image patches. The proposed framework could be solved using an alternating optimization strategy and it normally converges in only five outer iterations in the experiments. Our experimental results on the Chinese University of Hong Kong (CUHK) face sketch database, celebrity photos, CUHK Face Sketch FERET Database, IIIT-D Viewed Sketch Database, and forensic sketches demonstrate the effectiveness of our method for face sketch-photo synthesis. In addition, cross-database and database-dependent style-synthesis evaluations demonstrate the generalizability of this novel method and suggest promising solutions for face identification in forensic science.

Position and attitude tracking control for a quadrotor UAV.

PubMed

Xiong, Jing-Jing; Zheng, En-Hui

2014-05-01

A synthesis control method is proposed to perform the position and attitude tracking control of the dynamical model of a small quadrotor unmanned aerial vehicle (UAV), where the dynamical model is underactuated, highly-coupled and nonlinear. Firstly, the dynamical model is divided into a fully actuated subsystem and an underactuated subsystem. Secondly, a controller of the fully actuated subsystem is designed through a novel robust terminal sliding mode control (TSMC) algorithm, which is utilized to guarantee all state variables converge to their desired values in short time, the convergence time is so small that the state variables are acted as time invariants in the underactuated subsystem, and, a controller of the underactuated subsystem is designed via sliding mode control (SMC), in addition, the stabilities of the subsystems are demonstrated by Lyapunov theory, respectively. Lastly, in order to demonstrate the robustness of the proposed control method, the aerodynamic forces and moments and air drag taken as external disturbances are taken into account, the obtained simulation results show that the synthesis control method has good performance in terms of position and attitude tracking when faced with external disturbances. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Convergence analysis of two-node CMFD method for two-group neutron diffusion eigenvalue problem

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

Jeong, Yongjin; Park, Jinsu; Lee, Hyun Chul

2015-12-01

In this paper, the nonlinear coarse-mesh finite difference method with two-node local problem (CMFD2N) is proven to be unconditionally stable for neutron diffusion eigenvalue problems. The explicit current correction factor (CCF) is derived based on the two-node analytic nodal method (ANM2N), and a Fourier stability analysis is applied to the linearized algorithm. It is shown that the analytic convergence rate obtained by the Fourier analysis compares very well with the numerically measured convergence rate. It is also shown that the theoretical convergence rate is only governed by the converged second harmonic buckling and the mesh size. It is also notedmore » that the convergence rate of the CCF of the CMFD2N algorithm is dependent on the mesh size, but not on the total problem size. This is contrary to expectation for eigenvalue problem. The novel points of this paper are the analytical derivation of the convergence rate of the CMFD2N algorithm for eigenvalue problem, and the convergence analysis based on the analytic derivations.« less

Visual acuity and visual skills in Malaysian children with learning disabilities

PubMed Central

Muzaliha, Mohd-Nor; Nurhamiza, Buang; Hussein, Adil; Norabibas, Abdul-Rani; Mohd-Hisham-Basrun, Jaafar; Sarimah, Abdullah; Leo, Seo-Wei; Shatriah, Ismail

2012-01-01

Background: There is limited data in the literature concerning the visual status and skills in children with learning disabilities, particularly within the Asian population. This study is aimed to determine visual acuity and visual skills in children with learning disabilities in primary schools within the suburban Kota Bharu district in Malaysia. Methods: We examined 1010 children with learning disabilities aged between 8–12 years from 40 primary schools in the Kota Bharu district, Malaysia from January 2009 to March 2010. These children were identified based on their performance in a screening test known as the Early Intervention Class for Reading and Writing Screening Test conducted by the Ministry of Education, Malaysia. Complete ocular examinations and visual skills assessment included near point of convergence, amplitude of accommodation, accommodative facility, convergence break and recovery, divergence break and recovery, and developmental eye movement tests for all subjects. Results: A total of 4.8% of students had visual acuity worse than 6/12 (20/40), 14.0% had convergence insufficiency, 28.3% displayed poor accommodative amplitude, and 26.0% showed signs of accommodative infacility. A total of 12.1% of the students had poor convergence break, 45.7% displayed poor convergence recovery, 37.4% showed poor divergence break, and 66.3% were noted to have poor divergence recovery. The mean horizontal developmental eye movement was significantly prolonged. Conclusion: Although their visual acuity was satisfactory, nearly 30% of the children displayed accommodation problems including convergence insufficiency, poor accommodation, and accommodative infacility. Convergence and divergence recovery are the most affected visual skills in children with learning disabilities in Malaysia. PMID:23055674

Total Synthesis of Avrainvilleol.

PubMed

Wegener, Aaron; Miller, Kenneth A

2017-11-03

The first total synthesis of the marine natural product avrainvilleol is reported. The total synthesis features the first application of the transition-metal-free coupling of a tosyl hydrazone and a boronic acid to the preparation of a complex natural product, and the first example of this coupling with a hindered diortho substituted hydrazone substrate.

Total synthesis of (-)-strychnine.

PubMed

Kaburagi, Yosuke; Tokuyama, Hidetoshi; Fukuyama, Tohru

2004-08-25

Total synthesis of (-)-strychnine is described. Notable features of our synthesis include (1) palladium-catalyzed coupling of the indole and vinyl epoxide moieties, (2) synthesis of the nine-membered cyclic amine derivative from the diol precursor in a one-pot procedure, and (3) transannular cyclization of the nine-membered cyclic amine.

SAM-dependent enzyme-catalysed pericyclic reactions in natural product biosynthesis

NASA Astrophysics Data System (ADS)

Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-Cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K. N.; Tang, Yi

2017-09-01

Pericyclic reactions—which proceed in a concerted fashion through a cyclic transition state—are among the most powerful synthetic transformations used to make multiple regioselective and stereoselective carbon-carbon bonds. They have been widely applied to the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centres. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples (the intramolecular Diels-Alder reaction, and the Cope and the Claisen rearrangements) have been characterized. Here we report a versatile S-adenosyl-L-methionine (SAM)-dependent enzyme, LepI, that can catalyse stereoselective dehydration followed by three pericyclic transformations: intramolecular Diels-Alder and hetero-Diels-Alder reactions via a single ambimodal transition state, and a retro-Claisen rearrangement. Together, these transformations lead to the formation of the dihydropyran core of the fungal natural product, leporin. Combined in vitro enzymatic characterization and computational studies provide insight into how LepI regulates these bifurcating biosynthetic reaction pathways by using SAM as the cofactor. These pathways converge to the desired biosynthetic end product via the (SAM-dependent) retro-Claisen rearrangement catalysed by LepI. We expect that more pericyclic biosynthetic enzymatic transformations remain to be discovered in naturally occurring enzyme ‘toolboxes’. The new role of the versatile cofactor SAM is likely to be found in other examples of enzyme catalysis.

Self-consistent field for fragmented quantum mechanical model of large molecular systems.

PubMed

Jin, Yingdi; Su, Neil Qiang; Xu, Xin; Hu, Hao

2016-01-30

Fragment-based linear scaling quantum chemistry methods are a promising tool for the accurate simulation of chemical and biomolecular systems. Because of the coupled inter-fragment electrostatic interactions, a dual-layer iterative scheme is often employed to compute the fragment electronic structure and the total energy. In the dual-layer scheme, the self-consistent field (SCF) of the electronic structure of a fragment must be solved first, then followed by the updating of the inter-fragment electrostatic interactions. The two steps are sequentially carried out and repeated; as such a significant total number of fragment SCF iterations is required to converge the total energy and becomes the computational bottleneck in many fragment quantum chemistry methods. To reduce the number of fragment SCF iterations and speed up the convergence of the total energy, we develop here a new SCF scheme in which the inter-fragment interactions can be updated concurrently without converging the fragment electronic structure. By constructing the global, block-wise Fock matrix and density matrix, we prove that the commutation between the two global matrices guarantees the commutation of the corresponding matrices in each fragment. Therefore, many highly efficient numerical techniques such as the direct inversion of the iterative subspace method can be employed to converge simultaneously the electronic structure of all fragments, reducing significantly the computational cost. Numerical examples for water clusters of different sizes suggest that the method shall be very useful in improving the scalability of fragment quantum chemistry methods. © 2015 Wiley Periodicals, Inc.

Synthesis and structural study of two new heparin-like hexasaccharides.

PubMed

Lucas, Ricardo; Angulo, Jesús; Nieto, Pedro M; Martín-Lomas, Manuel

2003-07-07

Two new heparin-like hexasaccharides, 5 and 6, have been synthesised using a convergent block strategy and their solution conformations have been determined by NMR spectroscopy and molecular modelling. Both hexasaccharides contain the basic structural motif of the regular region of heparin but with negative charge distributions which have been designed to get insight into the mechanism of fibroblast growth factors (FGFs) activation.

Indole synthesis by palladium-catalyzed tandem allylic isomerization - furan Diels-Alder reaction.

PubMed

Xu, Jie; Wipf, Peter

2017-08-30

A Pd(0)-catalyzed elimination of an allylic acetate generates a π-allyl complex that is postulated to initiate a novel intramolecular Diels-Alder cycloaddition to a tethered furan (IMDAF). Under the reaction conditions, this convergent, microwave-accelerated cascade process provides substituted indoles in moderate to good yields after Pd-hydride elimination, aromatization by dehydration, and in situ N-Boc cleavage.

Going beyond LTM in the MTL: A Synthesis of Neuropsychological and Neuroimaging Findings on the Role of the Medial Temporal Lobe in Memory and Perception

ERIC Educational Resources Information Center

Graham, Kim S.; Barense, Morgan D.; Lee, Andy C. H.

2010-01-01

Studies in rats and non-human primates suggest that medial temporal lobe (MTL) structures play a role in perceptual processing, with the hippocampus necessary for spatial discrimination, and the perirhinal cortex for object discrimination. Until recently, there was little convergent evidence for analogous functional specialisation in humans, or…

Natural Product Total Synthesis in the Organic Laboratory: Total Synthesis of Caffeic Acid Phenethyl Ester (CAPE), a Potent 5-Lipoxygenase Inhibitor from Honeybee Hives

ERIC Educational Resources Information Center

Touaibia, Mohamed; Guay, Michel

2011-01-01

Natural products play a critical role in modern organic synthesis and learning synthetic techniques is an important component of the organic laboratory experience. In addition to traditional one-step organic synthesis laboratories, a multistep natural product synthesis is an interesting experiment to challenge students. The proposed three-step…

Total Synthesis of Bryostatins. Development of Methodology for Atom-Economic and Stereoselective Synthesis of the C-ring Subunit

PubMed Central

Trost, Barry M.; Frontier, Alison J.; Thiel, Oliver R.; Yang, Hanbiao; Dong, Guangbin

2012-01-01

Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for stereoselective assembly of the C-ring subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the C-ring subunit of bryostatins. PMID:21793057

Impact of post-Born lensing on the CMB

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

Pratten, Geraint; Lewis, Antony, E-mail: G.Pratten@Sussex.ac.uk, E-mail: antony@cosmologist.info

Lensing of the CMB is affected by post-Born lensing, producing corrections to the convergence power spectrum and introducing field rotation. We show numerically that the lensing convergence power spectrum is affected at the ∼< 0.2% level on accessible scales, and that this correction and the field rotation are negligible for observations with arcminute beam and noise levels ∼> 1 μK arcmin. The field rotation generates ∼ 2.5% of the total lensing B-mode polarization amplitude (0.2% in power on small scales), but has a blue spectrum on large scales, making it highly subdominant to the convergence B modes on scales wheremore » they are a source of confusion for the signal from primordial gravitational waves. Since the post-Born signal is non-linear, it also generates a bispectrum with the convergence. We show that the post-Born contributions to the bispectrum substantially change the shape predicted from large-scale structure non-linearities alone, and hence must be included to estimate the expected total signal and impact of bispectrum biases on CMB lensing reconstruction quadratic estimators and other observables. The field-rotation power spectrum only becomes potentially detectable for noise levels || 1 μK arcmin, but its bispectrum with the convergence may be observable at ∼ 3σ with Stage IV observations. Rotation-induced and convergence-induced B modes are slightly correlated by the bispectrum, and the bispectrum also produces additional contributions to the lensed BB power spectrum.« less

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides

PubMed Central

Rana, Neha; Kumar, Manish; Khatri, Vinod; Maity, Jyotirmoy

2017-01-01

Conversion of D-glucose to 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose, which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-xylofuranose. A convenient environment friendly Novozyme®-435 catalyzed selective acetylation methodology has been developed for the separation of an epimeric mixture of ribo- and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5-O-acetyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribo- and xylofuranose obtained by enzymatic acetylation, has been confirmed by an X-ray study on their corresponding 4-C-p-toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility. PMID:29062429

Enzymatic separation of epimeric 4-C-hydroxymethylated furanosugars: Synthesis of bicyclic nucleosides.

PubMed

Rana, Neha; Kumar, Manish; Khatri, Vinod; Maity, Jyotirmoy; Prasad, Ashok K

2017-01-01

Conversion of D-glucose to 4- C- hydroxymethyl-1,2- O -isopropylidene-α-D-ribofuranose, which is a key precursor for the synthesis of different types of bicyclic/spiro nucleosides, led to the formation of an inseparable 1:1 mixture of the desired product and 4- C- hydroxymethyl-1,2- O -isopropylidene-α-D-xylofuranose. A convenient environment friendly Novozyme ® -435 catalyzed selective acetylation methodology has been developed for the separation of an epimeric mixture of ribo - and xylotrihydroxyfuranosides in quantitative yields. The structure of both the monoacetylated epimers, i.e., 5- O -acetyl-4- C -hydroxymethyl-1,2- O -isopropylidene-α-D-ribo- and xylofuranose obtained by enzymatic acetylation, has been confirmed by an X-ray study on their corresponding 4- C - p -toluenesulfonyloxymethyl derivatives. Furthermore, the two separated epimers were used for the convergent synthesis of two different types of bicyclic nucleosides, which confirms their synthetic utility.

Synthetic Studies of Complex Immunostimulants from Quillaja saponaria: Synthesis of the Potent Clinical Immunoadjuvant QS-21Aapi

PubMed Central

Kim, Yong-Jae; Wang, Pengfei; Navarro-Villalobos, Mauricio; Rohde, Bridget D.; Derryberry, JohnMark; Gin, David Y.

2008-01-01

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21Aapi in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues. PMID:16953631

Neurobiology of autism gene products: towards pathogenesis and drug targets.

PubMed

Kleijer, Kristel T E; Schmeisser, Michael J; Krueger, Dilja D; Boeckers, Tobias M; Scheiffele, Peter; Bourgeron, Thomas; Brose, Nils; Burbach, J Peter H

2014-03-01

The genetic heterogeneity of autism spectrum disorders (ASDs) is enormous, and the neurobiology of proteins encoded by genes associated with ASD is very diverse. Revealing the mechanisms on which different neurobiological pathways in ASD pathogenesis converge may lead to the identification of drug targets. The main objective is firstly to outline the main molecular networks and neuronal mechanisms in which ASD gene products participate and secondly to answer the question how these converge. Finally, we aim to pinpoint drug targets within these mechanisms. Literature review of the neurobiological properties of ASD gene products with a special focus on the developmental consequences of genetic defects and the possibility to reverse these by genetic or pharmacological interventions. The regulation of activity-dependent protein synthesis appears central in the pathogenesis of ASD. Through sequential consequences for axodendritic function, neuronal disabilities arise expressed as behavioral abnormalities and autistic symptoms in ASD patients. Several known ASD gene products have their effect on this central process by affecting protein synthesis intrinsically, e.g., through enhancing the mammalian target of rapamycin (mTOR) signal transduction pathway or through impairing synaptic function in general. These are interrelated processes and can be targeted by compounds from various directions: inhibition of protein synthesis through Lovastatin, mTOR inhibition using rapamycin, or mGluR-related modulation of synaptic activity. ASD gene products may all feed into a central process of translational control that is important for adequate glutamatergic regulation of dendritic properties. This process can be modulated by available compounds but may also be targeted by yet unexplored routes.

Concise, Enantioselective Total Synthesis of (-)-Alstonerine

PubMed Central

Miller, Kenneth A.

2008-01-01

A novel enantioselective total synthesis of (-)-alstonerine has been completed that requires only 1 5 steps from L-tryptophan. The synthesis features the first application of a Pauson-Khand reaction t o synthesize an azabridged bicyclic skeleton. PMID:17298078

Thermal synthesis apparatus

DOEpatents

Fincke, James R [Idaho Falls, ID; Detering, Brent A [Idaho Falls, ID

2009-08-18

An apparatus for thermal conversion of one or more reactants to desired end products includes an insulated reactor chamber having a high temperature heater such as a plasma torch at its inlet end and, optionally, a restrictive convergent-divergent nozzle at its outlet end. In a thermal conversion method, reactants are injected upstream from the reactor chamber and thoroughly mixed with the plasma stream before entering the reactor chamber. The reactor chamber has a reaction zone that is maintained at a substantially uniform temperature. The resulting heated gaseous stream is then rapidly cooled by passage through the nozzle, which "freezes" the desired end product(s) in the heated equilibrium reaction stage, or is discharged through an outlet pipe without the convergent-divergent nozzle. The desired end products are then separated from the gaseous stream.

Mathematics of the total alkalinity-pH equation - pathway to robust and universal solution algorithms: the SolveSAPHE package v1.0.1

NASA Astrophysics Data System (ADS)

Munhoven, G.

2013-08-01

The total alkalinity-pH equation, which relates total alkalinity and pH for a given set of total concentrations of the acid-base systems that contribute to total alkalinity in a given water sample, is reviewed and its mathematical properties established. We prove that the equation function is strictly monotone and always has exactly one positive root. Different commonly used approximations are discussed and compared. An original method to derive appropriate initial values for the iterative solution of the cubic polynomial equation based upon carbonate-borate-alkalinity is presented. We then review different methods that have been used to solve the total alkalinity-pH equation, with a main focus on biogeochemical models. The shortcomings and limitations of these methods are made out and discussed. We then present two variants of a new, robust and universally convergent algorithm to solve the total alkalinity-pH equation. This algorithm does not require any a priori knowledge of the solution. SolveSAPHE (Solver Suite for Alkalinity-PH Equations) provides reference implementations of several variants of the new algorithm in Fortran 90, together with new implementations of other, previously published solvers. The new iterative procedure is shown to converge from any starting value to the physical solution. The extra computational cost for the convergence security is only 10-15% compared to the fastest algorithm in our test series.

Drosophila fragile X mental retardation protein and metabotropic glutamate receptor A convergently regulate the synaptic ratio of ionotropic glutamate receptor subclasses.

PubMed

Pan, Luyuan; Broadie, Kendal S

2007-11-07

A current hypothesis proposes that fragile X mental retardation protein (FMRP), an RNA-binding translational regulator, acts downstream of glutamatergic transmission, via metabotropic glutamate receptor (mGluR) G(q)-dependent signaling, to modulate protein synthesis critical for trafficking ionotropic glutamate receptors (iGluRs) at synapses. However, direct evidence linking FMRP and mGluR function with iGluR synaptic expression is limited. In this study, we use the Drosophila fragile X model to test this hypothesis at the well characterized glutamatergic neuromuscular junction (NMJ). Two iGluR classes reside at this synapse, each containing common GluRIIC (III), IID and IIE subunits, and variable GluRIIA (A-class) or GluRIIB (B-class) subunits. In Drosophila fragile X mental retardation 1 (dfmr1) null mutants, A-class GluRs accumulate and B-class GluRs are lost, whereas total GluR levels do not change, resulting in a striking change in GluR subclass ratio at individual synapses. The sole Drosophila mGluR, DmGluRA, is also expressed at the NMJ. In dmGluRA null mutants, both iGluR classes increase, resulting in an increase in total synaptic GluR content at individual synapses. Targeted postsynaptic dmGluRA overexpression causes the exact opposite GluR phenotype to the dfmr1 null, confirming postsynaptic GluR subtype-specific regulation. In dfmr1; dmGluRA double null mutants, there is an additive increase in A-class GluRs, and a similar additive impact on B-class GluRs, toward normal levels in the double mutants. These results show that both dFMRP and DmGluRA differentially regulate the abundance of different GluR subclasses in a convergent mechanism within individual postsynaptic domains.

Computational and Physical Analysis of Catalytic Compounds

NASA Astrophysics Data System (ADS)

Wu, Richard; Sohn, Jung Jae; Kyung, Richard

2015-03-01

Nanoparticles exhibit unique physical and chemical properties depending on their geometrical properties. For this reason, synthesis of nanoparticles with controlled shape and size is important to use their unique properties. Catalyst supports are usually made of high-surface-area porous oxides or carbon nanomaterials. These support materials stabilize metal catalysts against sintering at high reaction temperatures. Many studies have demonstrated large enhancements of catalytic behavior due to the role of the oxide-metal interface. In this paper, the catalyzing ability of supported nano metal oxides, such as silicon oxide and titanium oxide compounds as catalysts have been analyzed using computational chemistry method. Computational programs such as Gamess and Chemcraft has been used in an effort to compute the efficiencies of catalytic compounds, and bonding energy changes during the optimization convergence. The result illustrates how the metal oxides stabilize and the steps that it takes. The graph of the energy computation step(N) versus energy(kcal/mol) curve shows that the energy of the titania converges faster at the 7th iteration calculation, whereas the silica converges at the 9th iteration calculation.

Total Synthesis of (±)-Cis-Trikentrin B via Intermolecular 6,7-Indole Aryne Cycloaddition and Stille Cross-Coupling.

PubMed

Chandrasoma, Nalin; Brown, Neil; Brassfield, Allen; Nerurkar, Alok; Suarez, Susana; Buszek, Keith R

2013-02-20

An efficient total synthesis of the annulated indole natural product (±)- cis -trikentrin B was accomplished by means of a regioselectively generated 6,7-indole aryne cycloaddition via selective metal-halogen exchange from a 5,6,7-tribromoindole. The unaffected C-5 bromine was subsequently used for a Stille cross-coupling to install the butenyl side chain and complete the synthesis. This strategy provides rapid access into the trikentrins and the related herbindoles, and represents another application of this methodology to natural products total synthesis. The required 5,6,7-indole aryne precursor was prepared using the Leimgruber-Batcho indole synthesis.

A Continuum of Progress: Applications of N-Hetereocyclic Carbene Catalysis in Total Synthesis

PubMed Central

Izquierdo, Javier; Hutson, Gerri E.; Cohen, Daniel T.; Scheidt, Karl A.

2013-01-01

N-Heterocyclic carbene (NHC) catalyzed transformations have emerged as powerful tactics for the construction of complex molecules. Since Stetter’s report in 1975 of the total synthesis of cis-jasmon and dihydrojasmon by using carbene catalysis, the use of NHCs in total synthesis has grown rapidly, particularly over the last decade. This renaissance is undoubtedly due to the recent developments in NHC-catalyzed reactions, including new benzoin, Stetter, homoenolate, and aroylation processes. These transformations employ typical as well as Umpolung types of bond disconnections and have served as the key step in several new total syntheses. This Minireview highlights these reports and captures the excitement and emerging synthetic utility of carbene catalysis in total synthesis. PMID:23074146

Toward (-)-Enterocin: An Improved Cuprate Barbier Protocol To Overcome Strain and Sterical Hindrance.

PubMed

Rizzo, Antonio; Trauner, Dirk

2018-04-06

An approach toward (-)-enterocin, an antibiotic isolated from Streptomyces hygroscopicus, is described. Its compact, heavily oxidized protoadamantane core represents a daunting challenge for an efficient synthesis. Convergent assembly of its 2-oxabicyclo[3.3.1]nonane core with a cuprate-mediated Barbier reaction is disclosed. Its functionalization to a suitable substrate for a biomimetic aldol to close the final ring of the natural product is evaluated.

Reflections on the Batesian synthesis.

PubMed

Sivin, Nathan

2009-01-01

The argument in "Medicine and the Soul of Science" can be strengthened by understanding that what used to be called "the Western intellectual tradition" is a hodgepodge of Middle Eastern, Greek, Indian, Chinese, and other approaches and methods that converged in the Islamic world before ca. 1000 CE when Europeans began to borrow and adapt it, and by integrating the results of recent research on all of these scientific, technological, and medical traditions.

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.

Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack.

PubMed

Fügi, Matthias A; Gunasekera, Kapila; Ochsenreiter, Torsten; Guan, Xueli; Wenk, Markus R; Mäser, Pascal

2014-05-01

Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas's disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile.

Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack

PubMed Central

Fügi, Matthias A.; Gunasekera, Kapila; Ochsenreiter, Torsten; Guan, Xueli; Wenk, Markus R.; Mäser, Pascal

2014-01-01

Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas’s disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile. PMID:24627128

Convergent, modular expression of ebony and tan in the mimetic wing patterns of Heliconius butterflies.

PubMed

Ferguson, Laura C; Maroja, Luana; Jiggins, Chris D

2011-12-01

The evolution of pigmentation in vertebrates and flies has involved repeated divergence at a small number of genes related to melanin synthesis. Here, we study insect melanin synthesis genes in Heliconius butterflies, a group characterised by its diversity of wing patterns consisting of black (melanin), and yellow and red (ommochrome) pigmented scales. Consistent with their respective biochemical roles in Drosophila melanogaster, ebony is upregulated in non-melanic wing regions destined to be pigmented red whilst tan is upregulated in melanic regions. Wing regions destined to be pigmented yellow, however, are downregulated for both genes. This pattern is conserved across multiple divergent and convergent phenotypes within the Heliconii, suggesting a conserved mechanism for the development of black, red and yellow pattern elements across the genus. Linkage mapping of five melanin biosynthesis genes showed that, in contrast to other organisms, these genes do not control pattern polymorphism. Thus, the pigmentation genes themselves are not the locus of evolutionary change but lie downstream of a wing pattern regulatory factor. The results suggest a modular system in which particular combinations of genes are switched on whenever red, yellow or black pattern elements are favoured by natural selection for diverse and mimetic wing patterns. © Springer-Verlag 2011

Using Convergent and Divergent Tasks to Improve Writing and Language Learning Motivation

ERIC Educational Resources Information Center

Marashi, Hamid; Tahan-Shizari, Parissa

2015-01-01

This study was an attempt to investigate the comparative impact of convergent and divergent condition tasks on EFL learners' writing and motivation. Sixty female intermediate EFL learners were selected from among a total number of 90 through their performance on a sample piloted PET and further homogenized in terms of their writing and motivation.…

General Strategy for Synthesis of C-19 Methyl-Substituted Sarpagine/Macroline/Ajmaline Indole Alkaloids Including Total Synthesis of 19(S),20(R)-Dihydroperaksine, 19(S),20(R)-Dihydroperaksine-17-al, and Peraksine

PubMed Central

2015-01-01

A detailed account of the development of a general strategy for synthesis of the C-19 methyl-substituted alkaloids including total synthesis of 19(S),20(R)-dihydroperaksine-17-al (1), 19(S),20(R)-dihydroperaksine (2), and peraksine (6) is presented. Efforts directed toward the total synthesis of macrosalhine chloride (5) are also reported. Important to success is the sequence of chemical reactions which include a critical haloboration reaction, regioselective hydroboration, and controlled oxidation (to provide sensitive enolizable aldehydes at C-20). In addition, the all-important Pd-catalyzed α-vinylation reaction has been extended to a chiral C-19 alkyl-substituted substrate for the first time. Synthesis of the advanced intermediate 64 completes an improved formal total synthesis of talcarpine (26) and provides a starting point for synthesis of macroline-related alkaloids 27–31. Similarly, extension of this synthetic strategy in the ring A oxygenated series should provide easy access to the northern hemisphere 32b of the bisindoles angustricraline, alstocraline, and foliacraline (Figure 4). PMID:25247616

Samarium Diiodide-Mediated Reactions in Total Synthesis

PubMed Central

Nicolaou, K. C.; Ellery, Shelby P.; Chen, Jason S.

2009-01-01

Introduced by Henri Kagan more than three decades ago, samarium diiodide (SmI2) has found increasing applications in chemical synthesis. This single-electron reducing agent has been particularly useful in C–C bond formations, including those found in total synthesis endeavors. This Review highlights selected applications of SmI2 in total synthesis, with special emphasis on novel transformations and mechanistic considerations. The examples discussed are both illustrative of the power of this reagent in complex molecule construction and inspirational for the design of synthetic strategies toward such targets, both natural and designed. PMID:19714695

The chemical energy unit partial oxidation reactor operation simulation modeling

NASA Astrophysics Data System (ADS)

Mrakin, A. N.; Selivanov, A. A.; Batrakov, P. A.; Sotnikov, D. G.

2018-01-01

The chemical energy unit scheme for synthesis gas, electric and heat energy production which is possible to be used both for the chemical industry on-site facilities and under field conditions is represented in the paper. The partial oxidation reactor gasification process mathematical model is described and reaction products composition and temperature determining algorithm flow diagram is shown. The developed software product verification showed good convergence of the experimental values and calculations according to the other programmes: the temperature determining relative discrepancy amounted from 4 to 5 %, while the absolute composition discrepancy ranged from 1 to 3%. The synthesis gas composition was found out practically not to depend on the supplied into the partial oxidation reactor (POR) water vapour enthalpy and compressor air pressure increase ratio. Moreover, air consumption coefficient α increase from 0.7 to 0.9 was found out to decrease synthesis gas target components (carbon and hydrogen oxides) specific yield by nearly 2 times and synthesis gas target components required ratio was revealed to be seen in the water vapour specific consumption area (from 5 to 6 kg/kg of fuel).

Total synthesis of bryostatins: the development of methodology for the atom-economic and stereoselective synthesis of the ring C subunit.

PubMed

Trost, Barry M; Frontier, Alison J; Thiel, Oliver R; Yang, Hanbiao; Dong, Guangbin

2011-08-22

Bryostatins, a family of structurally complicated macrolides, exhibit an exceptional range of biological activities. The limited availability and structural complexity of these molecules makes development of an efficient total synthesis particularly important. This article describes our initial efforts towards the total synthesis of bryostatins, in which chemoselective and atom-economical methods for the stereoselective assembly of the ring C subunit were developed. A Pd-catalyzed tandem alkyne-alkyne coupling/6-endo-dig cyclization sequence was explored and successfully pursued in the synthesis of a dihydropyran ring system. Elaboration of this methodology ultimately led to a concise synthesis of the ring C subunit of bryostatins. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cosmological constraints from the convergence 1-point probability distribution

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

Patton, Kenneth; Blazek, Jonathan; Honscheid, Klaus

2017-06-29

Here, we examine the cosmological information available from the 1-point probability density function (PDF) of the weak-lensing convergence field, utilizing fast l-picola simulations and a Fisher analysis. We find competitive constraints in the Ωm–σ8 plane from the convergence PDF with 188 arcmin 2 pixels compared to the cosmic shear power spectrum with an equivalent number of modes (ℓ < 886). The convergence PDF also partially breaks the degeneracy cosmic shear exhibits in that parameter space. A joint analysis of the convergence PDF and shear 2-point function also reduces the impact of shape measurement systematics, to which the PDF is lessmore » susceptible, and improves the total figure of merit by a factor of 2–3, depending on the level of systematics. Finally, we present a correction factor necessary for calculating the unbiased Fisher information from finite differences using a limited number of cosmological simulations.« less

Cosmological constraints from the convergence 1-point probability distribution

NASA Astrophysics Data System (ADS)

Patton, Kenneth; Blazek, Jonathan; Honscheid, Klaus; Huff, Eric; Melchior, Peter; Ross, Ashley J.; Suchyta, Eric

2017-11-01

We examine the cosmological information available from the 1-point probability density function (PDF) of the weak-lensing convergence field, utilizing fast L-PICOLA simulations and a Fisher analysis. We find competitive constraints in the Ωm-σ8 plane from the convergence PDF with 188 arcmin2 pixels compared to the cosmic shear power spectrum with an equivalent number of modes (ℓ < 886). The convergence PDF also partially breaks the degeneracy cosmic shear exhibits in that parameter space. A joint analysis of the convergence PDF and shear 2-point function also reduces the impact of shape measurement systematics, to which the PDF is less susceptible, and improves the total figure of merit by a factor of 2-3, depending on the level of systematics. Finally, we present a correction factor necessary for calculating the unbiased Fisher information from finite differences using a limited number of cosmological simulations.

[Technological convergence will quickly generate disruptive innovations in oncology].

PubMed

Coucke, Ph A

2016-06-01

Convergence between information and communication technology and recent developments in medical care will totally change the health care sector. The way we perform diagnosis, treatment and follow-up will undergo disruptive changes in a very near future. We intend to highlight this statement by a limited selection of examples of radical innovations, especially in the field of oncology. To be totally disruptive and to illustrate the concept of "lateral power" - especially cognitive distribution - the list of references is only made up of internet links. Anyone - patients included - can easily and instantly access to this information everywhere.

The first total synthesis of sporiolide A.

PubMed

Du, Yuguo; Chen, Qi; Linhardt, Robert J

2006-10-27

The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound.

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)

Cognitive Load Reduces Perceived Linguistic Convergence Between Dyads.

PubMed

Abel, Jennifer; Babel, Molly

2017-09-01

Speech convergence is the tendency of talkers to become more similar to someone they are listening or talking to, whether that person is a conversational partner or merely a voice heard repeating words. To elucidate the nature of the mechanisms underlying convergence, this study uses different levels of task difficulty on speech convergence within dyads collaborating on a task. Dyad members had to build identical LEGO® constructions without being able to see each other's construction, and with each member having half of the instructions required to complete the construction. Three levels of task difficulty were created, with five dyads at each level (30 participants total). Task difficulty was also measured using completion time and error rate. Listeners who heard pairs of utterances from each dyad judged convergence to be occurring in the Easy condition and to a lesser extent in the Medium condition, but not in the Hard condition. Amplitude envelope acoustic similarity analyses of the same utterance pairs showed that convergence occurred in dyads with shorter completion times and lower error rates. Together, these results suggest that while speech convergence is a highly variable behavior, it may occur more in contexts of low cognitive load. The relevance of these results for the current automatic and socially-driven models of convergence is discussed.

Asymmetric total synthesis of cladosporin and isocladosporin.

PubMed

Zheng, Huaiji; Zhao, Changgui; Fang, Bowen; Jing, Peng; Yang, Juan; Xie, Xingang; She, Xuegong

2012-07-06

The first asymmetric total syntheses of cladosporin and isocladosporin were accomplished in 8 steps with 8% overall yield and 10 steps with 26% overall yield, respectively. The relative configuration of isocladosporin was determined via this total synthesis.

A Global comparison of surface soil characteristics across five cities: A test of the urban ecosystem convergence hypothesis.

Treesearch

Richard V. Pouyat; Ian D. Yesilonis; Miklos Dombos; Katalin Szlavecz; Heikki Setala; Sarel Cilliers; Erzsebet Hornung; D. Johan Kotze; Stephanie Yarwood

2015-01-01

As part of the Global Urban Soil Ecology and Education Network and to test the urban ecosystem convergence hypothesis, we report on soil pH, organic carbon (OC), total nitrogen (TN), phosphorus (P), and potassium (K) measured in four soil habitat types (turfgrass, ruderal, remnant, and reference) in five metropolitan areas (Baltimore, Budapest,...

Latin America Report No. 2701.

DTIC Science & Technology

1983-06-30

Federal Police Investigate Socialist Convergence Activities (0 ESTADO DE SAO PAULO, various dates) 45 National Operation Ackel Confirms Action...Convergence Condemns Investigation Headquarters Invaded 50 Lan-Chile Losses for 1982 Total $30 Million (EL MERCURI0, 2 Jun 83) 51 Haitian...Text] A FORMER Acklins Islander today sent a telegram to the Prime Minister asking for a thorough investigation into activity of light aircraft at

Approximating the linear quadratic optimal control law for hereditary systems with delays in the control

NASA Technical Reports Server (NTRS)

Milman, Mark H.

1987-01-01

The fundamental control synthesis issue of establishing a priori convergence rates of approximation schemes for feedback controllers for a class of distributed parameter systems is addressed within the context of hereditary systems. Specifically, a factorization approach is presented for deriving approximations to the optimal feedback gains for the linear regulator-quadratic cost problem associated with time-varying functional differential equations with control delays. The approach is based on a discretization of the state penalty which leads to a simple structure for the feedback control law. General properties of the Volterra factors of Hilbert-Schmidt operators are then used to obtain convergence results for the controls, trajectories and feedback kernels. Two algorithms are derived from the basic approximation scheme, including a fast algorithm, in the time-invariant case. A numerical example is also considered.

Approximating the linear quadratic optimal control law for hereditary systems with delays in the control

NASA Technical Reports Server (NTRS)

Milman, Mark H.

1988-01-01

The fundamental control synthesis issue of establishing a priori convergence rates of approximation schemes for feedback controllers for a class of distributed parameter systems is addressed within the context of hereditary schemes. Specifically, a factorization approach is presented for deriving approximations to the optimal feedback gains for the linear regulator-quadratic cost problem associated with time-varying functional differential equations with control delays. The approach is based on a discretization of the state penalty which leads to a simple structure for the feedback control law. General properties of the Volterra factors of Hilbert-Schmidt operators are then used to obtain convergence results for the controls, trajectories and feedback kernels. Two algorithms are derived from the basic approximation scheme, including a fast algorithm, in the time-invariant case. A numerical example is also considered.

Convergent solid-phase synthesis of hirudin.

PubMed

Goulas, Spyros; Gatos, Dimitrios; Barlos, Kleomenis

2006-02-01

Hirudin variant 1 (HV1), a small protein consisting of 65 amino acids and three disulfide bonds, was synthesized by using Fmoc-based convergent methods on 2-chlorotrityl resin (CLTR). The linear sequence was assembled by the sequential condensation of 7 protected fragments, on the resin-bound 55-65 fragment. The conditions of fragment assembly were carefully studied to determine the most efficient synthetic protocol. Crude reduced [Cys(16, 28)(Acm)]-HV1 thus obtained was easily purified to homogeneity by RP-HPLC. Disulfide bridges were successfully formed by a two-step procedure, involving an oxidative folding step to form Cys(6)-Cys(14) and Cys(22)-Cys(39) linkages, followed by iodine oxidation to form the Cys(16)-Cys(28) bond. The correct disulfide bond alignment was established by peptide mapping using Staphylococcus aureus V8 protease at pH 4.5.

Changes in the accommodation-convergence relationship after the Artisan phakic intraocular lens implantation for myopic patients.

PubMed

Ryu, Ik Hee; Han, Jinu; Lee, Hyung Keun; Kim, Jin Kook; Han, Sueng-Han

2014-04-01

To evaluate the change of accommodation-convergence parameters after implantation of Artisan phakic intraocular lens (PIOL). Prospective study for the patients with the Artisan PIOL implantation was performed. A total of 37 patients (3 males and 34 females) enrolled the study. Preoperatively, convergence amplitude, the stimulus accommodative convergence per unit of accommodation (AC/A) ratio and the near point of convergence (NPC) were evaluated. After the Artisan PIOL implantation, the identical evaluations were repeated at 1 week, 1, 3, and 6 months after the surgery. Mean age was 24.3 ± 4.8 years old, and preoperative refractive error was -8.92 ± 4.13 diopters (D). After the implantation, mean refractive errors significantly decreased to within ±1.00 D, and noticeable complications were not found. The convergence amplitude and the stimulus AC/A ratio increased 1 month after the surgery, but progressively stabilized afterward to near preoperative values. NPC didn't show any significant change over follow-up period up to 6 months. These results regarding implantation of the Artisan PIOL revealed the increase of accommodation-convergence relationship within first 1 month after the surgery, but progressive stabilization was noted during follow-up periods.

Survey of the Acoustic near Field of Three Nozzles at a Pressure Ratio of 30

NASA Technical Reports Server (NTRS)

Mull, Harold R; Erickson, John C , Jr

1957-01-01

The sound pressures radiating from the exhaust streams of two convergent-divergent and one convergent nozzle were measured. Exit diameters were 1.206 in. for the expanded nozzle and 0.625 in. for the convergent nozzle. The results are presented in a series of contour maps of overall and fine 1/3-octave-band sound pressures. The location of the source of the noise in each 1/3-octave band in the frequency range of 30 to 16,000 cps and the total power radiated were determined and compared with those of subsonic jets.

SAM-Dependent Enzyme-Catalysed Pericyclic Reactions in Natural Product Biosynthesis

PubMed Central

Ohashi, Masao; Liu, Fang; Hai, Yang; Chen, Mengbin; Tang, Man-cheng; Yang, Zhongyue; Sato, Michio; Watanabe, Kenji; Houk, K. N.; Tang, Yi

2017-01-01

Pericyclic reactions are among the most powerful synthetic transformations to make multiple regioselective and stereoselective carbon-carbon bonds1. These reactions have been widely applied for the synthesis of biologically active complex natural products containing contiguous stereogenic carbon centers2–6. Despite the prominence of pericyclic reactions in total synthesis, only three naturally existing enzymatic examples, intramolecular Diels-Alder (IMDA) reaction7, Cope8 and Claisen rearrangements9, have been characterized. Here, we report the discovery of a S-adenosyl-L-methionine (SAM) dependent enzyme LepI that can catalyse stereoselective dehydration, bifurcating IMDA/hetero-DA (HDA) reactions via an ambimodal transition state, and a [3,3]-sigmatropic retro-Claisen rearrangement leading to the formation of dihydopyran core in the fungal natural product leporin10. Combined in vitro enzymatic characterization and computational studies provide evidence and mechanistic insight about how the O-methyltransferase-like protein LepI regulates the bifurcating biosynthetic reaction pathways (“direct” HDA and “byproduct recycle” IMDA/retro-Claisen reaction pathways) by utilizing SAM as the cofactor in order to converge to the desired biosynthetic end product. This work highlights that LepI is the first example of an enzyme catalysing a (SAM-dependent) retro-Claisen rearrangement. We suggest that more pericyclic biosynthetic enzymatic transformations are yet to be discovered in the intriguing enzyme toolboxes in Nature11, and propose an ever expanding role of the versatile cofactor SAM in enzyme catalysis. PMID:28902839

Synthesis of substituted isoquinolines utilizing palladium-catalyzed α-arylation of ketones

PubMed Central

Donohoe, Timothy J.; Pilgrim, Ben S.; Jones, Geraint R.; Bassuto, José A.

2012-01-01

The utilization of sequential palladium-catalyzed α-arylation and cyclization reactions provides a general approach to an array of isoquinolines and their corresponding N-oxides. This methodology allows the convergent combination of readily available precursors in a regioselective manner and in excellent overall yields. This powerful route to polysubstituted isoquinolines, which is not limited to electron rich moieties, also allows rapid access to analogues of biologically active compounds. PMID:22753504

From a remarkable manifestation of polar effects in a radical fragmentation to the convergent synthesis of highly functionalized ketones.

PubMed

Debien, Laurent; Zard, Samir Z

2013-03-13

A new radical addition/C-C bond fragmentation process is reported. Vinyl carbinols derived from 2-methyl-2-phenylpropanal react with radicals generated from xanthates to give the corresponding ketones. The radical cleavage reaction proceeds under mild conditions, in good to high yield, and in the presence of the unprotected carbinol. Highly functionalized 1,5-diketones and pyridines are readily available using this approach.

Recruiting the Students to Fight Cancer: Total Synthesis of Goniothalamin

ERIC Educational Resources Information Center

Nahra, Fady; Riant, Olivier

2015-01-01

A modified total synthesis of (S)-goniothalamin is described for an advanced course in organic chemistry. This experiment gives students an opportunity to handle organometallic reagents and perform an enzymatic kinetic resolution and a metathesis reaction, all in the same synthesis. Furthermore, students learn flame-drying techniques for the…

The First Total Synthesis of Sporiolide A

PubMed Central

Chen, Qi; Linhardt, Robert J.

2014-01-01

The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound. PMID:17064018

Dearomatization Strategies in the Synthesis of Complex Natural Products

PubMed Central

Roche, Stéphane P.; Porco, John A.

2014-01-01

Evolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemo-selective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three-dimensional molecular architectures. PMID:21506209

Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General Protocol for the Formal Total Synthesis of (±)-Strychnine and the Total Synthesis of (±)-Akuammicine.

PubMed

Feng, Liang-Wen; Ren, Hai; Xiong, Hu; Wang, Pan; Wang, Lijia; Tang, Yong

2017-03-06

A ligand-promoted catalytic [4+2] annulation reaction using indole derivatives and donor-acceptor (D-A) cyclobutanes is reported, thus providing an efficient and atom-economical access to versatile cyclohexa-fused indolines with excellent levels of diastereoselectivity and a broad substrate scope. In the presence of a chiral SaBOX ligand, excellent enantioselectivity was realized with up to 94 % ee. This novel synthetic method is applied as a general protocol for the total synthesis of (±)-akuammicine and the formal total synthesis of (±)-strychnine from the same common-core scaffold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An Extension Convergent Validity Study of the "Systematic Screening for Behavior Disorders" and the Achenbach "Teacher's Report Form" with Middle and High School Students with Emotional Disturbances

ERIC Educational Resources Information Center

Benner, Gregory J.; Uhing, Brad M.; Pierce, Corey D.; Beaudoin, Kathleen M.; Ralston, Nicole C.; Mooney, Paul

2009-01-01

We sought to extend instrument validation research for the Systematic Screening for Behavior Disorders (SSBD) (Walker & Severson, 1990) using convergent validation techniques. Associations between Critical Events, Adaptive Behavior, and Maladaptive Behavior indices of the SSBD were examined in relation to syndrome, broadband, and total scores…

Total Synthesis of (+)- and (±)-Hosieine A.

PubMed

Huang, Yu-Wen; Kong, Ke; Wood, John

2018-05-03

Described here is a concise total synthesis of the highly potent nicotinic acetylcholine receptor antagonist hosieine A in racemic ((±)-2) and enantioenriched ((+)-2) forms. The synthesis requires only 7-steps and features a telescoped reaction sequence initiated by a gold-catalyzed Rautenstrauch reaction. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Jet-nozzle-expansion Ratio on Drag of Parabolic Afterbodies

NASA Technical Reports Server (NTRS)

Englert, Gerald W; Vargo, Donald J; Cubbison, Robert W

1954-01-01

The interaction of the flow from one convergent and two convergent-divergent nozzles on parabolic afterbodies was studied at free-stream Mach numbers of 2.0, 1.6, and 0.6 over a range of jet pressure ratio. The influence of the jet on boattail and base drag was very pronounced. Study of the total external afterbody drag values at supersonic speeds indicated that, over most of the high-pressure-ratio range, increasing the nozzle design expansion ratio increased the drag even though the boattail area was reduced. Increasing the pressure ratio tended to increase slightly the total-drag increment caused by angle-of-attack operation.

Before hierarchy: the rise and fall of Stephen Jay Gould's first macroevolutionary synthesis.

PubMed

Dresow, Max W

2017-06-01

Few of Stephen Jay Gould's accomplishments in evolutionary biology have received more attention than his hierarchical theory of evolution, which postulates a causal discontinuity between micro- and macroevolutionary events. But Gould's hierarchical theory was his second attempt to supply a theoretical framework for macroevolutionary studies-and one he did not inaugurate until the mid-1970s. In this paper, I examine Gould's first attempt: a proposed fusion of theoretical morphology, multivariate biometry and the experimental study of adaptation in fossils. This early "macroevolutionary synthesis" was predicated on the notion that parallelism and convergence dominate the history of higher taxa, and moreover, that they can be explained in terms of adaptation leading to mechanical improvement. In this paper, I explore the origins and contents of Gould's first macroevolutionary synthesis, as well as the reasons for its downfall. In addition, I consider how various developments during the mid-1970s led Gould to identify hierarchy and constraint as the leading themes of macroevolutionary studies-and adaptation as a macroevolutionary red herring.

Ising Critical Behavior of Inhomogeneous Curie-Weiss Models and Annealed Random Graphs

NASA Astrophysics Data System (ADS)

Dommers, Sander; Giardinà, Cristian; Giberti, Claudio; van der Hofstad, Remco; Prioriello, Maria Luisa

2016-11-01

We study the critical behavior for inhomogeneous versions of the Curie-Weiss model, where the coupling constant {J_{ij}(β)} for the edge {ij} on the complete graph is given by {J_{ij}(β)=β w_iw_j/( {sum_{kin[N]}w_k})}. We call the product form of these couplings the rank-1 inhomogeneous Curie-Weiss model. This model also arises [with inverse temperature {β} replaced by {sinh(β)} ] from the annealed Ising model on the generalized random graph. We assume that the vertex weights {(w_i)_{iin[N]}} are regular, in the sense that their empirical distribution converges and the second moment converges as well. We identify the critical temperatures and exponents for these models, as well as a non-classical limit theorem for the total spin at the critical point. These depend sensitively on the number of finite moments of the weight distribution. When the fourth moment of the weight distribution converges, then the critical behavior is the same as on the (homogeneous) Curie-Weiss model, so that the inhomogeneity is weak. When the fourth moment of the weights converges to infinity, and the weights satisfy an asymptotic power law with exponent {τ} with {τin(3,5)}, then the critical exponents depend sensitively on {τ}. In addition, at criticality, the total spin {S_N} satisfies that {S_N/N^{(τ-2)/(τ-1)}} converges in law to some limiting random variable whose distribution we explicitly characterize.

An appraisal of convergence failures in the application of logistic regression model in published manuscripts.

PubMed

Yusuf, O B; Bamgboye, E A; Afolabi, R F; Shodimu, M A

2014-09-01

Logistic regression model is widely used in health research for description and predictive purposes. Unfortunately, most researchers are sometimes not aware that the underlying principles of the techniques have failed when the algorithm for maximum likelihood does not converge. Young researchers particularly postgraduate students may not know why separation problem whether quasi or complete occurs, how to identify it and how to fix it. This study was designed to critically evaluate convergence issues in articles that employed logistic regression analysis published in an African Journal of Medicine and medical sciences between 2004 and 2013. Problems of quasi or complete separation were described and were illustrated with the National Demographic and Health Survey dataset. A critical evaluation of articles that employed logistic regression was conducted. A total of 581 articles was reviewed, of which 40 (6.9%) used binary logistic regression. Twenty-four (60.0%) stated the use of logistic regression model in the methodology while none of the articles assessed model fit. Only 3 (12.5%) properly described the procedures. Of the 40 that used the logistic regression model, the problem of convergence occurred in 6 (15.0%) of the articles. Logistic regression tends to be poorly reported in studies published between 2004 and 2013. Our findings showed that the procedure may not be well understood by researchers since very few described the process in their reports and may be totally unaware of the problem of convergence or how to deal with it.

Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis

PubMed Central

Noble, Adam; Roesner, Stefan

2016-01-01

Abstract Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly‐line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio‐ and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate‐controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps. PMID:27865037

Humanity and Environment Co-influence in the Shadow of Technological Convergence

NASA Astrophysics Data System (ADS)

Ezdina, Natalya

2017-11-01

Today one of the most important issues is the search for controlled ways of sustainable development of civilization, society, and a human. Previously, the development of society was determined by natural and evolutionary factors based on the principle of natural selection of living organisms and populations. However, as social institutions are developing, the technological factors of development, determined by the ideas about this phenomenon - the special arrangement of productive forces and the need to protect or change the environment, began to appear. The end of the 20th century was marked by the realization of a new, universal form of economic and technological synthesis - convergence, which, in the process of developing science and improving technology, became so comprehensive and widespread that today it can be called the force that transforms the environment. In this regard, it is convergent technologies that become the focus and the basis for research of the processes uniting the main spheres of human activity - science, society and technology, which will lead to a new form of interaction with the environment, conditioned not only by scientific and technological changes and social factors, but also new organizational forms of their interaction.

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block.

PubMed

Isoda, Yuta; Sasaki, Norihiko; Kitamura, Kei; Takahashi, Shuji; Manmode, Sujit; Takeda-Okuda, Naoko; Tamura, Jun-Ichi; Nokami, Toshiki; Itoh, Toshiyuki

2017-01-01

The total synthesis of TMG-chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block.

Global Flow Instability and Control IV Held in Crete, Greece on September 28-October 2, 2009: A Synthesis of Presentations and Discussions

DTIC Science & Technology

2009-09-01

non-uniform, stationary rotation / non- Distribution A: Approved for public release; distribution is unlimited. 8 stationary rotation , mass...Cayley spectral transformation as a means of rotating the basin of convergence of the Arnoldi algorithm. Instead of doing the inversion of the large...pair of counter rotating streamwise vortices embedded in uniform shear flow. Consistently with earlier work by the same group, the main present finding

Performance comparisons on spatial lattice algorithm and direct matrix inverse method with application to adaptive arrays processing

NASA Technical Reports Server (NTRS)

An, S. H.; Yao, K.

1986-01-01

Lattice algorithm has been employed in numerous adaptive filtering applications such as speech analysis/synthesis, noise canceling, spectral analysis, and channel equalization. In this paper the application to adaptive-array processing is discussed. The advantages are fast convergence rate as well as computational accuracy independent of the noise and interference conditions. The results produced by this technique are compared to those obtained by the direct matrix inverse method.

Cross-Cultural Adaptation and Psychometric Testing of the Brazilian Version of the Self-Care of Heart Failure Index Version 6.2

PubMed Central

Ávila, Christiane Wahast; Riegel, Barbara; Pokorski, Simoni Chiarelli; Camey, Suzi; Silveira, Luana Claudia Jacoby; Rabelo-Silva, Eneida Rejane

2013-01-01

Objective. To adapt and evaluate the psychometric properties of the Brazilian version of the SCHFI v 6.2. Methods. With the approval of the original author, we conducted a complete cross-cultural adaptation of the instrument (translation, synthesis, back translation, synthesis of back translation, expert committee review, and pretesting). The adapted version was named Brazilian version of the self-care of heart failure index v 6.2. The psychometric properties assessed were face validity and content validity (by expert committee review), construct validity (convergent validity and confirmatory factor analysis), and reliability. Results. Face validity and content validity were indicative of semantic, idiomatic, experimental, and conceptual equivalence. Convergent validity was demonstrated by a significant though moderate correlation (r = −0.51) on comparison with equivalent question scores of the previously validated Brazilian European heart failure self-care behavior scale. Confirmatory factor analysis supported the original three-factor model as having the best fit, although similar results were obtained for inadequate fit indices. The reliability of the instrument, as expressed by Cronbach's alpha, was 0.40, 0.82, and 0.93 for the self-care maintenance, self-care management, and self-care confidence scales, respectively. Conclusion. The SCHFI v 6.2 was successfully adapted for use in Brazil. Nevertheless, further studies should be carried out to improve its psychometric properties. PMID:24163765

Adiabatic-nuclei calculations of positron scattering from molecular hydrogen

DOE PAGES

Zammit, Mark Christian; Fursa, Dmitry V.; Savage, Jeremy S.; ...

2017-02-06

The single-center adiabatic-nuclei convergent close-coupling method is used to investigate positron collisions with molecular hydrogen (H 2) in the ground and first vibrationally excited states. Cross sections are presented over the energy range from 1 to 1000 eV for elastic scattering, vibrational excitation, total ionization, and the grand total cross section. The present adiabatic-nuclei positron- H 2 scattering length is calculated as A = $-$ 2.70 a 0 for the ground state and A = $-$ 3.16 a 0 for the first vibrationally excited state. The present elastic differential cross sections are also used to “correct” the low-energy grand totalmore » cross-section measurements of the Trento group [A. Zecca et al., Phys. Rev. A 80, 032702 (2009)] for the forward-angle-scattering effect. In general, the comparison with experiment is good. In conclusion, by performing convergence studies, we estimate that our R m = 1.448 a 0 fixed-nuclei results are converged to within ± 5 % for the major scattering integrated cross sections.« less

Flexible Approximation Model Approach for Bi-Level Integrated System Synthesis

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, Jaroslaw; Kim, Hongman; Ragon, Scott; Soremekun, Grant; Malone, Brett

2004-01-01

Bi-Level Integrated System Synthesis (BLISS) is an approach that allows design problems to be naturally decomposed into a set of subsystem optimizations and a single system optimization. In the BLISS approach, approximate mathematical models are used to transfer information from the subsystem optimizations to the system optimization. Accurate approximation models are therefore critical to the success of the BLISS procedure. In this paper, new capabilities that are being developed to generate accurate approximation models for BLISS procedure will be described. The benefits of using flexible approximation models such as Kriging will be demonstrated in terms of convergence characteristics and computational cost. An approach of dealing with cases where subsystem optimization cannot find a feasible design will be investigated by using the new flexible approximation models for the violated local constraints.

Total synthesis of (+)-achalensolide based on the rh(i)-catalyzed allenic Pauson-Khand-type reaction.

PubMed

Hirose, Toshiyuki; Miyakoshi, Naoki; Mukai, Chisato

2008-02-01

The first total synthesis of (+)-achalensolide was achieved from a commercially available d-(-)-isoascorbic acid. The known epoxide, derived from d-(-)-isoascorbic acid, was converted into the allenyne, the Rh(I)-catalyzed Pauson-Khand-type reaction of which directly provided the bicyclo[5.3.0]decane system, a core framework of the title natural product. The construction of the gamma-lactone moiety and some chemical modifications resulted in the completion of the total synthesis of (+)-achalensolide.

Listening to Another Sense: Somatosensory Integration in the Auditory System

PubMed Central

Wu, Calvin; Stefanescu, Roxana A.; Martel, David T.

2014-01-01

Conventionally, sensory systems are viewed as separate entities, each with its own physiological process serving a different purpose. However, many functions require integrative inputs from multiple sensory systems, and sensory intersection and convergence occur throughout the central nervous system. The neural processes for hearing perception undergo significant modulation by the two other major sensory systems, vision and somatosensation. This synthesis occurs at every level of the ascending auditory pathway: the cochlear nucleus, inferior colliculus, medial geniculate body, and the auditory cortex. In this review, we explore the process of multisensory integration from 1) anatomical (inputs and connections), 2) physiological (cellular responses), 3) functional, and 4) pathological aspects. We focus on the convergence between auditory and somatosensory inputs in each ascending auditory station. This review highlights the intricacy of sensory processing, and offers a multisensory perspective regarding the understanding of sensory disorders. PMID:25526698

Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations.

PubMed

Lewis, David A; Moghaddam, Bita

2006-10-01

Impairments in certain cognitive functions mediated by the dorsolateral prefrontal cortex, such as working memory, are core features of schizophrenia. Convergent findings suggest that these disturbances are associated with alterations in markers of inhibitory gamma-aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced gamma-aminobutyric acid synthesis is present in the subpopulation of gamma-aminobutyric acid neurons that express the calcium-binding protein parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the resulting impaired inhibitory regulation of pyramidal neurons contributes to a reduction in the synchronized neuronal activity that is required for working memory function. Several lines of evidence suggest that these changes may be either secondary to or exacerbated by impaired signaling via the N-methyl-d-aspartate class of glutamate receptors. These findings suggest specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.

Changes in the Accommodation-convergence Relationship after the Artisan Phakic Intraocular Lens Implantation for Myopic Patients

PubMed Central

Ryu, Ik Hee; Han, Jinu; Lee, Hyung Keun; Kim, Jin Kook

2014-01-01

Purpose To evaluate the change of accommodation-convergence parameters after implantation of Artisan phakic intraocular lens (PIOL). Methods Prospective study for the patients with the Artisan PIOL implantation was performed. A total of 37 patients (3 males and 34 females) enrolled the study. Preoperatively, convergence amplitude, the stimulus accommodative convergence per unit of accommodation (AC/A) ratio and the near point of convergence (NPC) were evaluated. After the Artisan PIOL implantation, the identical evaluations were repeated at 1 week, 1, 3, and 6 months after the surgery. Results Mean age was 24.3 ± 4.8 years old, and preoperative refractive error was -8.92 ± 4.13 diopters (D). After the implantation, mean refractive errors significantly decreased to within ±1.00 D, and noticeable complications were not found. The convergence amplitude and the stimulus AC/A ratio increased 1 month after the surgery, but progressively stabilized afterward to near preoperative values. NPC didn't show any significant change over follow-up period up to 6 months. Conclusions These results regarding implantation of the Artisan PIOL revealed the increase of accommodation-convergence relationship within first 1 month after the surgery, but progressive stabilization was noted during follow-up periods. PMID:24688257

An evaluation of clinical treatment of convergence insufficiency for children with reading difficulties.

PubMed

Dusek, Wolfgang A; Pierscionek, Barbara K; McClelland, Julie F

2011-08-11

The present study investigates two different treatment options for convergence insufficiency CI for a group of children with reading difficulties referred by educational institutes to a specialist eye clinic in Vienna. One hundred and thirty four subjects (aged 7-14 years) with reading difficulties were referred from an educational institute in Vienna, Austria for visual assessment. Each child was given either 8Δ base-in reading spectacles (n=51) or computerised home vision therapy (HTS) (n=51). Thirty two participants refused all treatment offered (clinical control group). A full visual assessment including reading speed and accuracy were conducted pre- and post-treatment. Factorial analyses demonstrated statistically significant changes between results obtained for visits 1 and 2 for total reading time, reading error score, amplitude of accommodation and binocular accommodative facility (within subjects effects) (p<0.05). Significant differences were also demonstrated between treatment groups for total reading time, reading error score and binocular accommodative facility (between subjects effects) (p<0.05). Reading difficulties with no apparent intellectual or psychological foundation may be due to a binocular vision anomaly such as convergence insufficiency. Both the HTS and prismatic correction are highly effective treatment options for convergence insufficiency. Prismatic correction can be considered an effective alternative to HTS.

Structural convergence properties of amorphous InGaZnO4 from simulated liquid-quench methods.

PubMed

Buchanan, Jacob C; Fast, Dylan B; Hanken, Benjamin E; Mustard, Thomas J L; Laurita, Geneva; Chiang, Tsung-Han; Keszler, Douglas A; Subramanian, Mas A; Wager, John F; Dolgos, Michelle R; Rustad, James R; Cheong, Paul Ha-Yeon

2017-11-14

The study of structural properties of amorphous structures is complicated by the lack of long-range order and necessitates the use of both cutting-edge computer modeling and experimental techniques. With regards to the computer modeling, many questions on convergence arise when trying to assess the accuracy of a simulated system. What cell size maximizes the accuracy while remaining computationally efficient? More importantly, does averaging multiple smaller cells adequately describe features found in bulk amorphous materials? How small is too small? The aims of this work are: (1) to report a newly developed set of pair potentials for InGaZnO 4 and (2) to explore the effects of structural parameters such as simulation cell size and numbers on the structural convergence of amorphous InGaZnO 4 . The total number of formula units considered over all runs is found to be the critical factor in convergence as long as the cell considered contains a minimum of circa fifteen formula units. There is qualitative agreement between these simulations and X-ray total scattering data - peak trends and locations are consistently reproduced while intensities are weaker. These new IGZO pair potentials are a valuable starting point for future structural refinement efforts.

Tectonics of the Andaman Sea Region

NASA Astrophysics Data System (ADS)

Curray, J. R.

2005-12-01

The Andaman Sea is an active backarc basin lying above and behind the Sunda subduction zone where convergence between the overriding Eurasian, Sunda or Southeast Asian plate and the subducting Indian and Australian plates is highly oblique. The effect of the oblique convergence has been formation of a sliver plate between the subduction zone and a complex right lateral fault system. The late Paleocene collision of Greater India and Asia with approximately normal convergence started clockwise rotation and bending of the northern and western Sunda Arc. The initial sliver fault, which probably started in the Eocene, extended through the outer arc ridge offshore from Sumatra, through the present region of the Andaman Sea into the Sagaing fault in Myanmar. With more oblique convergence due to the rotation, the rate of strike slip motion increased and a series of extensional basins opened obliquely by the combination of backarc extension and the strike slip motion. These basins in sequence are the Mergui Basin starting in early Oligocene, the conjoined Alcock and Sewell Rises starting in early Miocene, East Basin separating the rises from the foot of the continental slope starting at the end of early Miocene; and finally in early Pliocene at ~ 4 Ma, the present sliver plate edge was formed, Alcock and Sewell Rises were separated by formation of the Central Andaman Basin, and the faulting moved onshore from the Mentawai Fault to the Sumatra Fault System bisecting Sumatra. The opening of each basin can be expressed in vectors with north and west components. The total of the north component vectors may be the total offset of the Sagaing Fault since early Oligocene, and the total of the west component vectors may explain the outward bulge in the alignment of the northwestern Sunda Arc. The present average convergence rate of the Andaman-Nicobar Ridge and India is about 28 to 38 mm/yr.

Decadal variability of the position and strength of the South Atlantic Convergence Zone and its relationship to precipitation variability and extremes over Southeastern Brazil

NASA Astrophysics Data System (ADS)

Zilli, M. T.; Carvalho, L. V.; Lintner, B. R.

2016-12-01

The South Atlantic Convergence Zone (SACZ) is a diagonally oriented zone of low-level convergence, convective cloudiness, and rainfall originating over South America and extending to the southeast over the Atlantic Ocean. The objective of this study is to investigate the role of variability in the position and strength of the SACZ in causing precipitation variability and extremes over the southeastern Brazilian coast (SE). To that end, we perform Empirical Orthogonal Function (EOF) analysis of total summer (DJF) precipitation from 1979 to 2013, using the National Center for Environmental Prediction (NCEP) Climate Forecast System Reanalysis (CFSR), at 0.5° spatial resolution. The first mode (EOF-1) explains 22.7% of total variance and is characterized by a dipole-like structure, with opposite signs over central South America and over central South Atlantic along the northern margin of the SACZ. The time-coefficient or principal component of EOF-1 indicates a transition from a predominantly negative phase over 1999 to 2005 to a predominantly positive phase after 2006. The positive phase is associated with an increase in total precipitation over the continent and a reduction over the central South Atlantic, along the northern margin of the SACZ. These results provide evidence of the poleward shift of the SACZ and weakening of convergence along its northern margin over the past decade, consistent with the observed recent trends in extreme precipitation over SE. Compositing reanalysis fields with respect to the PC of EOF-1 suggests changes in moisture availability and circulation that could have affected precipitation regimes over SE. In particular, an increase in available precipitable water may have enhanced convective activity over the southern portion of SE Brazil, whereas the weakening of the northerly winds may be responsible for the weakening of convergence over the northern flank of the SACZ, inhibiting convection in this region.

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

PubMed Central

Isoda, Yuta; Sasaki, Norihiko; Kitamura, Kei; Takahashi, Shuji; Manmode, Sujit; Takeda-Okuda, Naoko; Tamura, Jun-ichi

2017-01-01

The total synthesis of TMG-chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block. PMID:28684973

Total Synthesis and Structural Revision of Antibiotic CJ-16,264.

PubMed

Nicolaou, K C; Shah, Akshay A; Korman, Henry; Khan, Tabrez; Shi, Lei; Worawalai, Wisuttaya; Theodorakis, Emmanuel A

2015-08-03

The total synthesis and structural revision of antibiotic CJ-16,264 is described. Starting with citronellal, the quest for the target molecule featured a novel bis-transannular Diels-Alder reaction that casted stereoselectively the decalin system and included the synthesis of six isomers before demystification of its true structure. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective modular synthesis of cyclohexenones: total syntheses of (+)-crypto- and (+)-infectocaryone.

PubMed

Franck, Géraldine; Brödner, Kerstin; Helmchen, Günter

2010-09-03

A modular synthesis of cyclohexenones is described and applied to the first enantioselective total syntheses of (+)-crypto- and (+)-infectocaryone. Key steps in the synthesis of cyclohexenones are an iridium-catalyzed allylic alkylation, nucleophilic allylation, and ring-closing metathesis. On the way to (+)-cryptocaryone, a catch and release strategy involving an iodolactonization/elimination and a regioselective C-acylation were used.

Entropy and gravity concepts as new methodological indexes to investigate technological convergence: patent network-based approach.

PubMed

Cho, Yongrae; Kim, Minsung

2014-01-01

The volatility and uncertainty in the process of technological developments are growing faster than ever due to rapid technological innovations. Such phenomena result in integration among disparate technology fields. At this point, it is a critical research issue to understand the different roles and the propensity of each element technology for technological convergence. In particular, the network-based approach provides a holistic view in terms of technological linkage structures. Furthermore, the development of new indicators based on network visualization can reveal the dynamic patterns among disparate technologies in the process of technological convergence and provide insights for future technological developments. This research attempts to analyze and discover the patterns of the international patent classification codes of the United States Patent and Trademark Office's patent data in printed electronics, which is a representative technology in the technological convergence process. To this end, we apply the physical idea as a new methodological approach to interpret technological convergence. More specifically, the concepts of entropy and gravity are applied to measure the activities among patent citations and the binding forces among heterogeneous technologies during technological convergence. By applying the entropy and gravity indexes, we could distinguish the characteristic role of each technology in printed electronics. At the technological convergence stage, each technology exhibits idiosyncratic dynamics which tend to decrease technological differences and heterogeneity. Furthermore, through nonlinear regression analysis, we have found the decreasing patterns of disparity over a given total period in the evolution of technological convergence. This research has discovered the specific role of each element technology field and has consequently identified the co-evolutionary patterns of technological convergence. These new findings on the evolutionary patterns of technological convergence provide some implications for engineering and technology foresight research, as well as for corporate strategy and technology policy.

Asymmetric total synthesis of onoseriolide, bolivianine, and isobolivianine.

PubMed

Du, Biao; Yuan, Changchun; Yu, Tianzi; Yang, Li; Yang, Yang; Liu, Bo; Qin, Song

2014-02-24

In this article, we describe our efforts on the total synthesis of bolivianine (1) and isobolivianine (2), involving the synthesis of onoseriolide (3). The first generation synthesis of bolivianine was completed in 21 steps by following a chiral resolution strategy. Based on the potential biogenetic relationship between bolivianine (1), onoseriolide (3), and β-(E)-ocimene (8), the second generation synthesis of bolivianine was biomimetically achieved from commercially available (+)-verbenone in 14 steps. The improved total synthesis features an unprecedented palladium-catalyzed intramolecular cyclopropanation through an allylic metal carbene, for the construction of the ABC tricyclic system, and a Diels-Alder/intramolecular hetero-Diels-Alder (DA/IMHDA) cascade for installation of the EFG tricyclic skeleton with the correct stereochemistry. Transformation from bolivianine to isobolivianine was facilitated in the presence of acid. The biosynthetic mechanism and the excellent regio- and endo selectivities in the cascade are well supported by theoretical chemistry based on the DFT calculations. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modifications to the nozzle test chamber to extend nozzle static-test capability

NASA Technical Reports Server (NTRS)

Keyes, J. W.

1985-01-01

The nozzle test chamber was modified to provide a high-pressure-ratio nozzle static-test capability. Experiments were conducted to determine the range of the ratio of nozzle total pressure to chamber pressure and to make direct nozzle thrust measurements using a three-component strain-gage force balance. Pressure ratios from 3 to 285 were measured with several axisymmetric nozzles at a nozzle total pressure of 15 to 190 psia. Devices for measuring system mass flow were calibrated using standard axisymmetric convergent choked nozzles. System mass-flow rates up to 10 lbm/sec are measured. The measured thrust results of these nozzles are in good agreement with one-dimensional theoretical predictions for convergent nozzles.

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer

PubMed Central

2012-01-01

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from “pulling” coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives. PMID:22545027

Convergence of Free Energy Profile of Coumarin in Lipid Bilayer.

PubMed

Paloncýová, Markéta; Berka, Karel; Otyepka, Michal

2012-04-10

Atomistic molecular dynamics (MD) simulations of druglike molecules embedded in lipid bilayers are of considerable interest as models for drug penetration and positioning in biological membranes. Here we analyze partitioning of coumarin in dioleoylphosphatidylcholine (DOPC) bilayer, based on both multiple, unbiased 3 μs MD simulations (total length) and free energy profiles along the bilayer normal calculated by biased MD simulations (∼7 μs in total). The convergences in time of free energy profiles calculated by both umbrella sampling and z-constraint techniques are thoroughly analyzed. Two sets of starting structures are also considered, one from unbiased MD simulation and the other from "pulling" coumarin along the bilayer normal. The structures obtained by pulling simulation contain water defects on the lipid bilayer surface, while those acquired from unbiased simulation have no membrane defects. The free energy profiles converge more rapidly when starting frames from unbiased simulations are used. In addition, z-constraint simulation leads to more rapid convergence than umbrella sampling, due to quicker relaxation of membrane defects. Furthermore, we show that the choice of RESP, PRODRG, or Mulliken charges considerably affects the resulting free energy profile of our model drug along the bilayer normal. We recommend using z-constraint biased MD simulations based on starting geometries acquired from unbiased MD simulations for efficient calculation of convergent free energy profiles of druglike molecules along bilayer normals. The calculation of free energy profile should start with an unbiased simulation, though the polar molecules might need a slow pulling afterward. Results obtained with the recommended simulation protocol agree well with available experimental data for two coumarin derivatives.

In the eye of the beholder: Helmholtzian perception and the origins of Freud's 1900 theory of transference.

PubMed

Makari, G J

1994-01-01

Freud's 1900 theory of transference was indebted to the convergence of philosophy and physiology found in nineteenth-century theories of visual perception. The author maps out the post-Kantian philosophical and German physiological currents that gave rise to Hermann von Helmholtz's influential work on perception, and proposes that Freud's 1900 theory of transference was a creative synthesis of novel notions like unconscious wishing and psychic defense with a Helmholtzian model of visual illusion.

Enantioselective Syntheses of (−)-Alloyohimbane and (−)-Yohimbane by an Efficient Enzymatic Desymmetrization Process

PubMed Central

Ghosh, Arun K.; Sarkar, Anindya

2016-01-01

Enantioselective syntheses of (−)-alloyohimbane and (−)-yohimbane was accomplished in a convergent manner. The key step involved a modified mild protocol for the enantioselective enzymatic desymmetrization of meso-diacetate. The protocol provided convenient access to an optically active monoacetate in multi-gram scale in high enantiomeric purity. This monoacetate was converted to (−)-alloyohimbane. Reductive amination of the derived aldehyde causes the isomerization leading to the trans-product and allows the synthesis of (−)-yohimbane. PMID:28757804

Ru(II)-Catalyzed Cross-Coupling of Cyclopropenes with Diazo Compounds: Formation of Olefins from Two Different Carbene Precursors.

PubMed

Wang, Bo; Yi, Heng; Zhang, Hang; Sun, Tong; Zhang, Yan; Wang, Jianbo

2018-01-19

Formal carbene dimerization is a convergent method for the synthesis of alkenes. Herein, we report a Ru(II)-catalyzed carbene dimerization of cyclopropenes and diazo compounds. The yields are up to 97% and the stereoselectivity are up to >20:1. Mechanistically, it has been experimentally demonstrated that the catalyst reacts with cyclopropene first to generate a Ru(II)-carbene species, which is attacked by nucleophilic diazo substrate, followed by dinitrogen extrusion to form the double bond.

Phellilane L, Sesquiterpene Metabolite of Phellinus linteus: Isolation, Structure Elucidation, and Asymmetric Total Synthesis.

PubMed

Ota, Koichiro; Yamazaki, Ikuma; Saigoku, Takahiro; Fukui, Mei; Miyata, Tomoki; Kamaike, Kazuo; Shirahata, Tatsuya; Mizuno, Fumi; Asada, Yoshihisa; Hirotani, Masao; Ino, Chieko; Yoshikawa, Takafumi; Kobayashi, Yoshinori; Miyaoka, Hiroaki

2017-12-01

A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus ("Meshimakobu" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).

Reply to "Comment on `Route from discreteness to the continuum for the Tsallis q -entropy' "

NASA Astrophysics Data System (ADS)

Oikonomou, Thomas; Bagci, G. Baris

2018-06-01

It has been known for some time that the usual q -entropy Sq(n ) cannot be shown to converge to the continuous case. In Phys. Rev. E 97, 012104 (2018), 10.1103/PhysRevE.97.012104, we have shown that the discrete q -entropy S˜q(n ) converges to the continuous case when the total number of states are properly taken into account in terms of a convergence factor. Ou and Abe [previous Comment, Phys. Rev. E 97, 066101 (2018), 10.1103/PhysRevE.97.066101] noted that this form of the discrete q -entropy does not conform to the Shannon-Khinchin expandability axiom. As a reply, we note that the fulfillment or not of the expandability property by the discrete q -entropy strongly depends on the origin of the convergence factor, presenting an example in which S˜q(n ) is expandable.

Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery.

PubMed

Barbero, Margherita; Artuso, Emma; Prandi, Cristina

2018-01-01

Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Inositolphosphoglycan mediators structurally related to glycosyl phosphatidylinositol anchors: synthesis, structure and biological activity.

PubMed

Martín-Lomas, M; Khiar, N; García, S; Koessler, J L; Nieto, P M; Rademacher, T W

2000-10-02

The preparation of the pseudopentasaccharide 1a, an inositol-phosphoglycan (IPG) that contains the conserved linear structure of glycosyl phosphatidylinositol anchors (GPI anchors), was carried out by using a highly convergent 2+3-block synthesis approach which involves imidate and sulfoxide glycosylation reactions. The preferred solution conformation of this structure was determined by using NMR spectroscopy and molecular dynamics simulations prior to carrying out quantitative structure--activity relationship studies in connection with the insulin signalling process. The ability of 1a to stimulate lipogenesis in rat adipocytes as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1a did not show any significant activity, which may be taken as a strong indication that the GPI anchors are not the precursors of the IPG mediators.

Monte Carlo estimation of total variation distance of Markov chains on large spaces, with application to phylogenetics.

PubMed

Herbei, Radu; Kubatko, Laura

2013-03-26

Markov chains are widely used for modeling in many areas of molecular biology and genetics. As the complexity of such models advances, it becomes increasingly important to assess the rate at which a Markov chain converges to its stationary distribution in order to carry out accurate inference. A common measure of convergence to the stationary distribution is the total variation distance, but this measure can be difficult to compute when the state space of the chain is large. We propose a Monte Carlo method to estimate the total variation distance that can be applied in this situation, and we demonstrate how the method can be efficiently implemented by taking advantage of GPU computing techniques. We apply the method to two Markov chains on the space of phylogenetic trees, and discuss the implications of our findings for the development of algorithms for phylogenetic inference.

Protein chemical synthesis by α-ketoacid-hydroxylamine ligation.

PubMed

Harmand, Thibault J; Murar, Claudia E; Bode, Jeffrey W

2016-06-01

Total chemical synthesis of proteins allows researchers to custom design proteins without the complex molecular biology that is required to insert non-natural amino acids or the biocontamination that arises from methods relying on overexpression in cells. We describe a detailed procedure for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA ligation), using (S)-5-oxaproline (Opr) as a key building block. This protocol comprises two main parts: (i) the synthesis of peptide fragments by standard fluorenylmethoxycarbonyl (Fmoc) chemistry and (ii) the KAHA ligation between fragments containing Opr and a C-terminal peptide α-ketoacid. This procedure provides an alternative to native chemical ligation (NCL) that could be valuable for the synthesis of proteins, particularly targets that do not contain cysteine residues. The ligation conditions-acidic DMSO/H2O or N-methyl-2-pyrrolidinone (NMP)/H2O-are ideally suited for solubilizing peptide segments, including many hydrophobic examples. The utility and efficiency of the protocol is demonstrated by the total chemical synthesis of the mature betatrophin (also called ANGPTL8), a 177-residue protein that contains no cysteine residues. With this protocol, the total synthesis of the betatrophin protein has been achieved in around 35 working days on a multimilligram scale.

Total synthesis and stereochemical assignment of the salicylate antitumor macrolide lobatamide C(1).

PubMed

Shen, Ruichao; Lin, Cheng Ting; Porco, John A

2002-05-22

The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C is reported. The synthesis involves Cu(I)-mediated enamide formation and Na(2)CO(3)-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Macrolactonization was accomplished using a Mitsunobu protocol. The stereochemical assignment of lobatamide C was achieved by Mosher ester analysis and comparison with prepared stereoisomers.

Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)-Lundurine A.

PubMed

Nash, Aaron; Qi, Xiangbing; Maity, Pradip; Owens, Kyle; Tambar, Uttam K

2018-04-16

A novel vinylogous Pictet-Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scope and Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin.

PubMed

Dhayalan, Balamurugan; Mandal, Kalyaneswar; Rege, Nischay; Weiss, Michael A; Eitel, Simon H; Meier, Thomas; Schoenleber, Ralph O; Kent, Stephen B H

2017-01-31

We have systematically explored three approaches based on 9-fluorenylmethoxycarbonyl (Fmoc) chemistry solid phase peptide synthesis (SPPS) for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the "hybrid method", in which maximally protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide-thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[O-β-(Thr)] ester-linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS. The most effective method for the preparation of the 51 residue ester-linked polypeptide chain of ester insulin was the use of unprotected peptide-thioester segments, prepared from peptide-hydrazides synthesized by Fmoc chemistry SPPS, and condensed by native chemical ligation. High-resolution X-ray crystallography confirmed the disulfide pairings and three-dimensional structure of synthetic insulin lispro prepared from ester insulin lispro by this route. Further optimization of these pilot studies could yield an efficient total chemical synthesis of insulin lispro (Humalog) based on peptide synthesis by Fmoc chemistry SPPS. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Asymmetric negotiation in structured language games

NASA Astrophysics Data System (ADS)

Yang, Han-Xin; Wang, Wen-Xu; Wang, Bing-Hong

2008-02-01

We propose an asymmetric negotiation strategy to investigate the influence of high-degree agents on the agreement dynamics in a structured language game, the naming game. We introduce a model parameter, which governs the frequency of high-degree agents acting as speakers in communication. It is found that there exists an optimal value of the parameter that induces the fastest convergence to a global consensus on naming an object for both scale-free and small-world naming games. This phenomenon indicates that, although a strong influence of high-degree agents favors consensus achievement, very strong influences inhibit the convergence process, making it even slower than in the absence of influence of high-degree agents. Investigation of the total memory used by agents implies that there is some trade-off between the convergence speed and the required total memory. Other quantities, including the evolution of the number of different names and the relationship between agents’ memories and their degrees, are also studied. The results are helpful for better understanding of the dynamics of the naming game with asymmetric negotiation strategy.

An Investigation of Convergent-Divergent Diffusers at Mach Number 1.85

NASA Technical Reports Server (NTRS)

Wyatt, Demarquis D; Hunczak, Henry R

1947-01-01

An investigation has been conducted in the Cleveland 18- by 18-inch supersonic tunnel at a Mach number of 1.85 and angles of attack from 0 deg to 5 deg to determine optimum design configurations for a convergent-divergent type of supersonic diffuser with a subsonic diffuser of 5 deg included divergence angle. Total pressure recoveries in excess of theoretical recovery across a normal shock at a free-stream Mach number of 1.85 wore obtained with several configurations. The highest recovery for configurations without a cylindrical throat section was obtained with an inlet having an included convergence angle of 20 deg. Insertion of a 2-inch throat section between a 10 deg included angle inlet and the subsonic diffuser stabilized the shock inside the diffuser and resulted in recoveries as high as 0.838 free-stream total pressure at an angle of attack of 0 deg, corresponding to recovery of 92.4 percent of the kinetic energy of the free air stream. Use of the throat section also lessened the reduction in recovery of all configurations due to angle of attack.

Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H).

PubMed

Yokoya, Masashi; Kobayashi, Keiichiro; Sato, Mitsuhiro; Saito, Naoki

2015-08-06

The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendaño's protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I.

Glucocorticoid-induced skeletal muscle atrophy in vitro is attenuated by mechanical stimulation

NASA Technical Reports Server (NTRS)

Chromiak, J. A.; Vandenburgh, H. H.

1992-01-01

Glucocorticoids induce rapid atrophy of fast skeletal myofibers in vivo, and either weight lifting or endurance exercise reduces this atrophy by unknown mechanisms. We examined the effects of the synthetic glucocorticoid dexamethasone (Dex) on protein turnover in tissue-cultured avian fast skeletal myofibers and determined whether repetitive mechanical stretch altered the myofiber response to Dex. In static cultures after 3-5 days, 10(-8) M Dex decreased total protein content 42-74%, total protein synthesis rates 38-56%, mean myofiber diameter 35%, myosin heavy chain (MHC) content 86%, MHC synthesis rate 44%, and fibronectin synthesis rate 29%. Repetitive 10% stretch-relaxations of the cultured myofibers for 60 s every 5 min for 3-4 days prevented 52% of the Dex-induced decrease in protein content, 42% of the decrease in total protein synthesis rate, 77% of the decrease in MHC content, 42% of the decrease in MHC synthesis rate, and 67% of the decrease in fibronectin synthesis rate. This in vitro model system will complement in vivo studies in understanding the mechanism by which mechanical activity and glucocorticoids interact to regulate skeletal muscle growth.

On the convergence of difference approximations to scalar conservation laws

NASA Technical Reports Server (NTRS)

Osher, S.; Tadmor, E.

1985-01-01

A unified treatment of explicit in time, two level, second order resolution, total variation diminishing, approximations to scalar conservation laws are presented. The schemes are assumed only to have conservation form and incremental form. A modified flux and a viscosity coefficient are introduced and results in terms of the latter are obtained. The existence of a cell entropy inequality is discussed and such an equality for all entropies is shown to imply that the scheme is an E scheme on monotone (actually more general) data, hence at most only first order accurate in general. Convergence for total variation diminishing-second order resolution schemes approximating convex or concave conservation laws is shown by enforcing a single discrete entropy inequality.

The meaning and perceived value of mind-body practices for people living with HIV: a qualitative synthesis.

PubMed

Donald, Graeme; Lawrence, Maggie; Lorimer, Karen; Stringer, Jacqui; Flowers, Paul

2015-01-01

Mind-body practices (MBPs) are a subset of complementary medicine that represents a selection of self-care activities that may promote the health of people living with HIV (PLWH). No synthesis of qualitative research in this context, which might inform service provision and research priorities, has yet been published. A systematic search of electronic databases was conducted, identifying papers exploring the experience of MBPs in PLWH. During thematic synthesis, all text under the headings "results" or "findings" was scanned line by line, and discrete, meaningful units of text were extracted as data items. Categories were identified, and second- and third-order constructs were developed. Concerns related to control and self-management appeared in the convergence of participants' worlds with the medical world and in being pragmatic about selecting MBPs and goal setting. The themes developed suggest a desire for more holistic and person-centered care, arguably marginalized as a result of effective antiretroviral therapy. Copyright © 2015 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

New insights into the electrochemical behavior of acid orange 7: Convergent paired electrochemical synthesis of new aminonaphthol derivatives

NASA Astrophysics Data System (ADS)

Momeni, Shima; Nematollahi, Davood

2017-02-01

Electrochemical behavior of acid orange 7 has been exhaustively studied in aqueous solutions with different pH values, using cyclic voltammetry and constant current coulometry. This study has provided new insights into the mechanistic details, pH dependence and intermediate structure of both electrochemical oxidation and reduction of acid orange 7. Surprisingly, the results indicate that a same redox couple (1-iminonaphthalen-2(1H)-one/1-aminonaphthalen-2-ol) is formed from both oxidation and reduction of acid orange 7. Also, an additional purpose of this work is electrochemical synthesis of three new derivatives of 1-amino-4-(phenylsulfonyl)naphthalen-2-ol (3a-3c) under constant current electrolysis via electrochemical oxidation (and reduction) of acid orange 7 in the presence of arylsulfinic acids as nucleophiles. The results indicate that the electrogenerated 1-iminonaphthalen-2(1 H)-one participates in Michael addition reaction with arylsulfinic acids to form the 1-amino-3-(phenylsulfonyl)naphthalen-2-ol derivatives. The synthesis was carried out in an undivided cell equipped with carbon rods as an anode and cathode.

Asymmetric total synthesis of (+)-fusarisetin A via the intramolecular Pauson-Khand reaction.

PubMed

Huang, Jun; Fang, Lichao; Long, Rong; Shi, Li-Li; Shen, Hong-Juan; Li, Chuang-chuang; Yang, Zhen

2013-08-02

An asymmetic total synthesis of (+)-fusarisetin A has been achieved. The essential to our strategy was the application of the intramolecular Pauson-Khand reaction for the stereoselective construction of the trans-decalin subunit of (+)-fusarisetin A with a unique C16 quarternary chiral center. The developed chemistry offers an alternative to the IMDA reaction that has been used for fusarisetin A, and is applicable to analogue synthesis for biological evaluation.

Total synthesis of the cyclopeptide alkaloid abyssenine A. Application of inter- and intramolecular copper-mediated coupling reactions in organic synthesis.

PubMed

Toumi, Mathieu; Couty, François; Evano, Gwilherm

2007-11-23

The first total synthesis of the 15-membered ring cyclopeptide alkaloid abyssenine A 1 has been achieved with a longest linear sequence of 15 steps. Central to the synthetic approach was an efficient copper-mediated Ullmann coupling/Claisen rearrangement sequence allowing for both ipso and ortho functionalization of aromatic iodide 4. This sequence was used for the synthesis of the aromatic core. The synthetic utility of copper-catalyzed coupling reactions was further demonstrated to install the enamide with a concomitant straightforward macrocyclization starting from acyclic alpha-amido-omega-vinyl iodide 13.

Adaptive-gain fast super-twisting sliding mode fault tolerant control for a reusable launch vehicle in reentry phase.

PubMed

Zhang, Yao; Tang, Shengjing; Guo, Jie

2017-11-01

In this paper, a novel adaptive-gain fast super-twisting (AGFST) sliding mode attitude control synthesis is carried out for a reusable launch vehicle subject to actuator faults and unknown disturbances. According to the fast nonsingular terminal sliding mode surface (FNTSMS) and adaptive-gain fast super-twisting algorithm, an adaptive fault tolerant control law for the attitude stabilization is derived to protect against the actuator faults and unknown uncertainties. Firstly, a second-order nonlinear control-oriented model for the RLV is established by feedback linearization method. And on the basis a fast nonsingular terminal sliding mode (FNTSM) manifold is designed, which provides fast finite-time global convergence and avoids singularity problem as well as chattering phenomenon. Based on the merits of the standard super-twisting (ST) algorithm and fast reaching law with adaption, a novel adaptive-gain fast super-twisting (AGFST) algorithm is proposed for the finite-time fault tolerant attitude control problem of the RLV without any knowledge of the bounds of uncertainties and actuator faults. The important feature of the AGFST algorithm includes non-overestimating the values of the control gains and faster convergence speed than the standard ST algorithm. A formal proof of the finite-time stability of the closed-loop system is derived using the Lyapunov function technique. An estimation of the convergence time and accurate expression of convergence region are also provided. Finally, simulations are presented to illustrate the effectiveness and superiority of the proposed control scheme. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Constructing Molecular Complexity and Diversity: Total Synthesis of Natural Products of Biological and Medicinal Importance

PubMed Central

Nicolaou, K. C.; Hale, Christopher R. H.; Nilewski, Christian; Ioannidou, Heraklidia A.

2012-01-01

The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules—natural and designed—of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products—the organic molecules of nature—is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature’s molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years. PMID:22743704

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance.

PubMed

Nicolaou, K C; Hale, Christopher R H; Nilewski, Christian; Ioannidou, Heraklidia A

2012-08-07

The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules--natural and designed--of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products--the organic molecules of nature--is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature's molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years.

Low-protein, high-carbohydrate diet increases glucose uptake and fatty acid synthesis in brown adipose tissue of rats.

PubMed

Aparecida de França, Suélem; Pavani Dos Santos, Maísa; Nunes Queiroz da Costa, Roger Vinícius; Froelich, Mendalli; Buzelle, Samyra Lopes; Chaves, Valéria Ernestânia; Giordani, Morenna Alana; Pereira, Mayara Peron; Colodel, Edson Moleta; Marlise Balbinotti Andrade, Cláudia; Kawashita, Nair Honda

2014-04-01

The aim of this study was to evaluate glucose uptake and the contribution of glucose to fatty acid (FA) synthesis and the glycerol-3-phosphate (G3P) of triacylglycerol synthesis by interscapular brown adipose tissue (IBAT) of low-protein, high-carbohydrate (LPHC) diet-fed rats. LPHC (6% protein; 74% carbohydrate) or control (17% protein; 63% carbohydrate) diets were administered to rats (∼ 100 g) for 15 d. Total FA and G3P synthesis and the synthesis of FA and G3P from glucose were evaluated in vivo by (3)H2O and (14)C-glucose. Sympathetic neural contribution for FA synthesis was evaluated by comparing the synthesis in denervated (7 d before) IBAT with that of the contralateral innervated side. The insulin signaling and β3 adrenergic receptor (β3-AR) contents, as well as others, were determined by Western blot (Student's t test or analysis of variance; P ≤ 0.05). Total FA synthesis in IBAT was 133% higher in the LPHC group and was reduced 85% and 70% by denervation for the LPHC and control groups, respectively. Glucose uptake was 3.5-fold higher in the IBAT of LPHC rats than in that of the control rats, and the contribution of glucose to the total FA synthesis increased by 12% in control rats compared with 18% in LPHC rats. The LPHC diet increased the G3P generation from glucose by 270% and the insulin receptor content and the p-AKT insulin stimulation in IBAT by 120% and reduced the β3-AR content by 50%. The LPHC diet stimulated glucose uptake, both the total rates and the rates derived from glucose-dependent FA and G3P synthesis, by increasing the insulin sensitivity and the sympathetic flux, despite a reduction in the β3-AR content. Copyright © 2014 Elsevier Inc. All rights reserved.

Bioinspired total synthesis and structural revision of yuremamine, an alkaloid from the entheogenic plant Mimosa tenuiflora.

PubMed

Calvert, Matthew B; Sperry, Jonathan

2015-04-11

Guided by a biosynthetic hypothesis, a serendipitous total synthesis of yuremamine has resulted in its structural revision from the putative pyrroloindole (1) to the flavonoidal indole (2), which was initially proposed as a biosynthetic intermediate.

Catalytic asymmetric total synthesis of (+)-yohimbine.

PubMed

Mergott, Dustin J; Zuend, Stephan J; Jacobsen, Eric N

2008-03-06

The total synthesis of (+)-yohimbine was achieved in 11 steps and 14% overall yield. The absolute configuration was established through a highly enantioselective thiourea-catalyzed acyl-Pictet-Spengler reaction, and the remaining 4 stereocenters were set simultaneously in a substrate-controlled intramolecular Diels-Alder reaction.

Product Distribution from Precursor Bite Angle Variation in Multitopic Alkyne Metathesis: Evidence for a Putative Kinetic Bottleneck.

PubMed

Moneypenny, Timothy P; Yang, Anna; Walter, Nathan P; Woods, Toby J; Gray, Danielle L; Zhang, Yang; Moore, Jeffrey S

2018-05-02

In the dynamic synthesis of covalent organic frameworks and molecular cages, the typical synthetic approach involves heuristic methods of discovery. While this approach has yielded many remarkable products, the ability to predict the structural outcome of subjecting a multitopic precursor to dynamic covalent chemistry (DCC) remains a challenge in the field. The synthesis of covalent organic cages is a prime example of this phenomenon, where precursors designed with the intention of affording a specific product may deviate dramatically when the DCC synthesis is attempted. As such, rational design principles are needed to accelerate discovery in cage synthesis using DCC. Herein, we test the hypothesis that precursor bite angle contributes significantly to the energy landscape and product distribution in multitopic alkyne metathesis (AM). By subjecting a series of precursors with varying bite angles to AM, we experimentally demonstrate that the product distribution, and convergence toward product formation, is strongly dependent on this geometric attribute. Surprisingly, we discovered that precursors with the ideal bite angle (60°) do not afford the most efficient pathway to the product. The systematic study reported here illustrates how seemingly minor adjustments in precursor geometry greatly affect the outcome of DCC systems. This research illustrates the importance of fine-tuning precursor geometric parameters in order to successfully realize desirable targets.

Self-interrupted synthesis of sterically hindered aliphatic polyamide dendrimers

PubMed Central

Jishkariani, Davit; Timsina, Yam N.; Grama, Silvia; Gillani, Syeda S.; Divar, Masoumeh; Yadavalli, Srujana S.; Moussodia, Ralph-Olivier; Leowanawat, Pawaret; Berrios Camacho, Angely M.; Walter, Ricardo; Goulian, Mark; Klein, Michael L.; Percec, Virgil

2017-01-01

2,2-Bis(azidomethyl)propionic acid was prepared in four steps and 85% yield from the commercially available 2,2-bis(hydroxymethyl)propionic acid and used as the starting building block for the divergent, convergent, and double-stage convergent–divergent iterative methods for the synthesis of dendrimers and dendrons containing ethylenediamine (EDA), piperazine (PPZ), and methyl 2,2-bis(aminomethyl)propionate (COOMe) cores. These cores have the same multiplicity but different conformations. A diversity of synthetic methods were used for the synthesis of dendrimers and dendrons. Regardless of the method used, a self-interruption of the synthesis was observed at generation 4 for the dendrimer with an EDA core and at generation 5 for the one with a PPZ core, whereas for the COOMe core, self-interruption was observed at generation 6 dendron, which is equivalent to generation 5 dendrimer. Molecular modeling and molecular-dynamics simulations demonstrated that the observed self-interruption is determined by the backfolding of the azide groups at the periphery of the dendrimer. The latter conformation inhibits completely the heterogeneous hydrogenation of the azide groups catalyzed by 10% Pd/carbon as well as homogeneous hydrogenation by the Staudinger method. These self-terminated polyamide dendrimers are enzymatically and hydrolytically stable and also exhibit antimicrobial activity. Thus, these nanoscale constructs open avenues for biomedical applications. PMID:28270599

Reliability of the Balance Evaluation Systems Test (BESTest) and BESTest sections for adults with hemiparesis

PubMed Central

Rodrigues, Letícia C.; Marques, Aline P.; Barros, Paula B.; Michaelsen, Stella M.

2014-01-01

BACKGROUND: The Balance Evaluation Systems Test (BESTest) was recently created to allow the development of treatments according to the specific balance system affected in each patient. The Brazilian version of the BESTest has not been specifically tested after stroke. OBJECTIVE: To evaluate the intra- and inter-rater reliability and concurrent and convergent validity of the total score of the BESTest and BESTest sections for adults with hemiparesis after stroke. METHOD: The study included 16 subjects (61.1±7.5 years) with chronic hemiparesis (54.5±43.5 months after stroke). The BESTest was administered by two raters in the same week and one of the raters repeated the test after a one-week interval. Intraclass correlation coefficient (ICC) was calculated to assess intra- and interrater reliability. Concurrent validity with the Berg Balance Scale (BBS) and convergent validity with the Activities-specific Balance Confidence scale (ABC-Brazil) were assessed using Pearson's correlation coefficient. RESULTS: Both the BESTest total score (ICC=0.98) and the BESTest sections (ICC between 0.85 and 0.96) have excellent intrarater reliability. Interrater reliability for the total score was excellent (ICC=0.93) and, for the sections, it ranged between 0.71 and 0.94. The correlation coefficient between the BESTest and the BBS and ABC-Brazil were 0.78 and 0.59, respectively. CONCLUSIONS: The Brazilian version of the BESTest demonstrated adequate reliability when measured by sections and could identify what balance system was affected in patients after stroke. Concurrent validity was excellent with the BBS total score and good to excellent with the sections. The total scores but not the sections present adequate convergent validity with the ABC-Brazil. However, other psychometric properties should be further investigated. PMID:25003281

The Total Synthesis Problem of linear multivariable control. II - Unity feedback and the design morphism

NASA Technical Reports Server (NTRS)

Sain, M. K.; Antsaklis, P. J.; Gejji, R. R.; Wyman, B. F.; Peczkowski, J. L.

1981-01-01

Zames (1981) has observed that there is, in general, no 'separation principle' to guarantee optimality of a division between control law design and filtering of plant uncertainty. Peczkowski and Sain (1978) have solved a model matching problem using transfer functions. Taking into consideration this investigation, Peczkowski et al. (1979) proposed the Total Synthesis Problem (TSP), wherein both the command/output-response and command/control-response are to be synthesized, subject to the plant constraint. The TSP concept can be subdivided into a Nominal Design Problem (NDP), which is not dependent upon specific controller structures, and a Feedback Synthesis Problem (FSP), which is. Gejji (1980) found that NDP was characterized in terms of the plant structural matrices and a single, 'good' transfer function matrix. Sain et al. (1981) have extended this NDP work. The present investigation is concerned with a study of FSP for the unity feedback case. NDP, together with feedback synthesis, is understood as a Total Synthesis Problem.

Scope & Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin

PubMed Central

Dhayalan, Balamurugan; Mandal, Kalyaneswar; Rege, Nischay; Weiss, Michael A.; Eitel, Simon H.; Meier, Thomas; Schoenleber, Ralph O.; Kent, Stephen B.H.

2017-01-01

We have systematically explored three approaches based on Fmoc chemistry SPPS for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the ‘hybrid method’, in which maximally-protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide-thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[Oβ(Thr)] ester-linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS. The most effective method for the preparation of the 51 residue ester-linked polypeptide chain of ester insulin was the use of unprotected peptide-thioester segments, prepared from peptide-hydrazides synthesized by Fmoc chemistry SPPS, and condensed by native chemical ligation. High resolution X-ray crystallography confirmed the disulfide pairings and three-dimensional structure of synthetic insulin lispro prepared from ester insulin lispro by this route. Further optimization of these pilot studies should yield an effective total chemical synthesis of insulin lispro (Humalog) based on peptide synthesis by Fmoc chemistry SPPS. PMID:27905149

Entropy and Gravity Concepts as New Methodological Indexes to Investigate Technological Convergence: Patent Network-Based Approach

PubMed Central

Cho, Yongrae; Kim, Minsung

2014-01-01

The volatility and uncertainty in the process of technological developments are growing faster than ever due to rapid technological innovations. Such phenomena result in integration among disparate technology fields. At this point, it is a critical research issue to understand the different roles and the propensity of each element technology for technological convergence. In particular, the network-based approach provides a holistic view in terms of technological linkage structures. Furthermore, the development of new indicators based on network visualization can reveal the dynamic patterns among disparate technologies in the process of technological convergence and provide insights for future technological developments. This research attempts to analyze and discover the patterns of the international patent classification codes of the United States Patent and Trademark Office's patent data in printed electronics, which is a representative technology in the technological convergence process. To this end, we apply the physical idea as a new methodological approach to interpret technological convergence. More specifically, the concepts of entropy and gravity are applied to measure the activities among patent citations and the binding forces among heterogeneous technologies during technological convergence. By applying the entropy and gravity indexes, we could distinguish the characteristic role of each technology in printed electronics. At the technological convergence stage, each technology exhibits idiosyncratic dynamics which tend to decrease technological differences and heterogeneity. Furthermore, through nonlinear regression analysis, we have found the decreasing patterns of disparity over a given total period in the evolution of technological convergence. This research has discovered the specific role of each element technology field and has consequently identified the co-evolutionary patterns of technological convergence. These new findings on the evolutionary patterns of technological convergence provide some implications for engineering and technology foresight research, as well as for corporate strategy and technology policy. PMID:24914959

Total Synthesis of Adunctin B.

PubMed

Dethe, Dattatraya H; Dherange, Balu D

2018-03-16

Total synthesis of (±)-adunctin B, a natural product isolated from Piper aduncum (Piperaceae), has been achieved using two different strategies, in seven and three steps. The efficient approach features highly atom economical and diastereoselective Friedel-Crafts acylation, alkylation reaction and palladium catalyzed Wacker type oxidative cyclization.

Enantioselective total synthesis of hyperforin.

PubMed

Sparling, Brian A; Moebius, David C; Shair, Matthew D

2013-01-16

A modular, 18-step total synthesis of hyperforin is described. The natural product was quickly accessed using latent symmetry elements, whereby a group-selective, Lewis acid-catalyzed epoxide-opening cascade cyclization was used to furnish the bicyclo[3.3.1]nonane core and set two key quaternary stereocenters.

Clinical test responses to different orthoptic exercise regimes in typical young adults

PubMed Central

Horwood, Anna; Toor, Sonia

2014-01-01

Purpose The relative efficiency of different eye exercise regimes is unclear, and in particular the influences of practice, placebo and the amount of effort required are rarely considered. This study measured conventional clinical measures following different regimes in typical young adults. Methods A total of 156 asymptomatic young adults were directed to carry out eye exercises three times daily for 2 weeks. Exercises were directed at improving blur responses (accommodation), disparity responses (convergence), both in a naturalistic relationship, convergence in excess of accommodation, accommodation in excess of convergence, and a placebo regime. They were compared to two control groups, neither of which were given exercises, but the second of which were asked to make maximum effort during the second testing. Results Instruction set and participant effort were more effective than many exercises. Convergence exercises independent of accommodation were the most effective treatment, followed by accommodation exercises, and both regimes resulted in changes in both vergence and accommodation test responses. Exercises targeting convergence and accommodation working together were less effective than those where they were separated. Accommodation measures were prone to large instruction/effort effects and monocular accommodation facility was subject to large practice effects. Conclusions Separating convergence and accommodation exercises seemed more effective than exercising both systems concurrently and suggests that stimulation of accommodation and convergence may act in an additive fashion to aid responses. Instruction/effort effects are large and should be carefully controlled if claims for the efficacy of any exercise regime are to be made. PMID:24471739

Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review

PubMed Central

Rahman, Md Toufiqur; Phani Babu Tiruveedhula, Veera V. N.; Cook, James M.

2016-01-01

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of monomeric indole alkaloids. Herein is reviewed the enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the Alstonia genus of the Apocynaceae family. The monomeric units belong to the sarpagine, ajmaline, macroline, vobasine, and pleiocarpamine series. An up-to-date discussion of their isolation, characterization, biological activity as well as approaches to their partial and total synthesis by means of both synthetic and biosynthetic strategies are presented. PMID:27854259

Tidbits for the synthesis of bis(2-sulfanylethyl)amido (SEA) polystyrene resin, SEA peptides and peptide thioesters.

PubMed

Ollivier, Nathalie; Raibaut, Laurent; Blanpain, Annick; Desmet, Rémi; Dheur, Julien; Mhidia, Reda; Boll, Emmanuelle; Drobecq, Hervé; Pira, Silvain L; Melnyk, Oleg

2014-02-01

Protein total chemical synthesis enables the atom-by-atom control of the protein structure and therefore has a great potential for studying protein function. Native chemical ligation of C-terminal peptide thioesters with N-terminal cysteinyl peptides and related methodologies are central to the field of protein total synthesis. Consequently, methods enabling the facile synthesis of peptide thioesters using Fmoc-SPPS are of great value. Herein, we provide a detailed protocol for the preparation of bis(2-sulfanylethyl)amino polystyrene resin as a starting point for the synthesis of C-terminal bis(2-sulfanylethyl)amido peptides and of peptide thioesters derived from 3-mercaptopropionic acid. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.

The Mediterranean diet: health, science and society.

PubMed

Gerber, Mariette; Hoffman, Richard

2015-04-01

The Mediterranean diet (MD) emerged as a healthy food regimen long before it could be recognised which nutrients or foods were responsible for its observed benefits, and it was only in the middle of the last century that the first scientific approach 'The Seven Countries Study' appeared. Epidemiological and anthropological studies of the MD converged, first by investigating at single nutrients or foods, then by adopting the more holistic approach of dietary patterns (DP), and now with a molecular approach. These studies resulted in convincing evidence that a MD decreases the risk of all-cause mortality and cardiovascular mortality and incidence. A risk reduction of developing type 2 diabetes is probable. Evidence is less stringent for other metabolic diseases and all cancers but from possible to probable for some cancer sites. Although DP showed that the MD has to be considered in its totality, olive oil could have a specific role. Lifestyle factors such as physical activity for energy balance, outdoor life for vitamin D synthesis and conviviality are also probably partly responsible for the health benefits. The MD is a lifestyle well suited for coping not only with personal health but also with wider societal concerns in relation to environment, public health and economy.

Nanoparticle-plant interaction: Implications in energy, environment, and agriculture.

PubMed

Rai, Prabhat Kumar; Kumar, Vanish; Lee, SangSoo; Raza, Nadeem; Kim, Ki-Hyun; Ok, Yong Sik; Tsang, Daniel C W

2018-06-14

In the recent techno-scientific revolution, nanotechnology has gained popularity at a rapid pace in different sectors and disciplines, specifically environmental, sensing, bioenergy, and agricultural systems. Controlled, easy, economical, and safe synthesis of nanomaterials is desired for the development of new-age nanotechnology. In general, nanomaterial synthesis techniques, such as chemical synthesis, are not completely safe or environmentally friendly due to harmful chemicals used or to toxic by-products produced. Moreover, a few nanomaterials are present as by-product during washing process, which may accumulate in water, air, and soil system to pose serious threats to plants, animals, and microbes. In contrast, using plants for nanomaterial (especially nanoparticle) synthesis has proven to be environmentally safe and economical. The role of plants as a source of nanoparticles is also likely to expand the number of options for sustainable green renewable energy, especially in biorefineries. Despite several advantages of nanotechnology, the nano-revolution has aroused concerns in terms of the fate of nanoparticles in the environment because of the potential health impacts caused by nanotoxicity upon their release. In the present panoramic review, we discuss the possibility that a multitudinous array of nanoparticles may find applications convergent with human welfare based on the synthesis of diverse nanoparticles from plants and their extracts. The significance of plant-nanoparticle interactions has been elucidated further for nanoparticle synthesis, applications of nanoparticles, and the disadvantages of using plants for synthesizing nanoparticles. Finally, we discuss future prospects of plant-nanoparticle interactions in relation to the environment, energy, and agriculture with implications in nanotechnology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Stereoselective Total Synthesis of (±)-5- epi-Cyanthiwigin I via an Intramolecular Pauson-Khand Reaction as the Key Step.

PubMed

Chang, Yuanyuan; Shi, Linlin; Huang, Jun; Shi, Lili; Zhang, Zichun; Hao, Hong-Dong; Gong, Jianxian; Yang, Zhen

2018-05-09

A convenient approach to the construction of the 5-6-7 tricarbocyclic fused core structure of cyanthiwigins via a Co-mediated Pauson-Khand reaction as a key step has been developed. The cyathane core intermediate obtained by this strategy was used in the concise synthesis of (±)-5- epi-cyanthiwigin I. The developed chemistry paves the way for the total synthesis of structurally diverse cyanthiwigins.

A platform for the discovery of new macrolide antibiotics

NASA Astrophysics Data System (ADS)

Seiple, Ian B.; Zhang, Ziyang; Jakubec, Pavol; Langlois-Mercier, Audrey; Wright, Peter M.; Hog, Daniel T.; Yabu, Kazuo; Allu, Senkara Rao; Fukuzaki, Takehiro; Carlsen, Peter N.; Kitamura, Yoshiaki; Zhou, Xiang; Condakes, Matthew L.; Szczypiński, Filip T.; Green, William D.; Myers, Andrew G.

2016-05-01

The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

Parallel evolution of the glycogen synthase 1 (muscle) gene Gys1 between Old World and New World fruit bats (Order: Chiroptera).

PubMed

Fang, Lu; Shen, Bin; Irwin, David M; Zhang, Shuyi

2014-10-01

Glycogen synthase, which catalyzes the synthesis of glycogen, is especially important for Old World (Pteropodidae) and New World (Phyllostomidae) fruit bats that ingest high-carbohydrate diets. Glycogen synthase 1, encoded by the Gys1 gene, is the glycogen synthase isozyme that functions in muscles. To determine whether Gys1 has undergone adaptive evolution in bats with carbohydrate-rich diets, in comparison to insect-eating sister bat taxa, we sequenced the coding region of the Gys1 gene from 10 species of bats, including two Old World fruit bats (Pteropodidae) and a New World fruit bat (Phyllostomidae). Our results show no evidence for positive selection in the Gys1 coding sequence on the ancestral Old World and the New World Artibeus lituratus branches. Tests for convergent evolution indicated convergence of the sequences and one parallel amino acid substitution (T395A) was detected on these branches, which was likely driven by natural selection.

Contribution to harmonic balance calculations of self-sustained periodic oscillations with focus on single-reed instruments.

PubMed

Farner, Snorre; Vergez, Christophe; Kergomard, Jean; Lizée, Aude

2006-03-01

The harmonic balance method (HBM) was originally developed for finding periodic solutions of electronical and mechanical systems under a periodic force, but has been adapted to self-sustained musical instruments. Unlike time-domain methods, this frequency-domain method does not capture transients and so is not adapted for sound synthesis. However, its independence of time makes it very useful for studying any periodic solution, whether stable or unstable, without care of particular initial conditions in time. A computer program for solving general problems involving nonlinearly coupled exciter and resonator, HARMBAL, has been developed based on the HBM. The method as well as convergence improvements and continuation facilities are thoroughly presented and discussed in the present paper. Applications of the method are demonstrated, especially on problems with severe difficulties of convergence: the Helmholtz motion (square signals) of single-reed instruments when no losses are taken into account, the reed being modeled as a simple spring.

A direct method for the synthesis of orthogonally protected furyl- and thienyl- amino acids.

PubMed

Hudson, Alex S; Caron, Laurent; Colgin, Neil; Cobb, Steven L

2015-04-01

The synthesis of unnatural amino acids plays a key part in expanding the potential application of peptide-based drugs and in the total synthesis of peptide natural products. Herein, we report a direct method for the synthesis of orthogonally protected 5-membered heteroaromatic amino acids.

Computational neuroanatomy of speech production.

PubMed

Hickok, Gregory

2012-01-05

Speech production has been studied predominantly from within two traditions, psycholinguistics and motor control. These traditions have rarely interacted, and the resulting chasm between these approaches seems to reflect a level of analysis difference: whereas motor control is concerned with lower-level articulatory control, psycholinguistics focuses on higher-level linguistic processing. However, closer examination of both approaches reveals a substantial convergence of ideas. The goal of this article is to integrate psycholinguistic and motor control approaches to speech production. The result of this synthesis is a neuroanatomically grounded, hierarchical state feedback control model of speech production.

Control of nonlinear systems using terminal sliding modes

NASA Technical Reports Server (NTRS)

Venkataraman, S. T.; Gulati, S.

1992-01-01

The development of an approach to control synthesis for robust robot operations in unstructured environments is discussed. To enhance control performance with full model information, the authors introduce the notion of terminal convergence and develop control laws based on a class of sliding modes, denoted as terminal sliders. They demonstrate that terminal sliders provide robustness to parametric uncertainty without having to resort to high-frequency control switching, as in the case of conventional sliders. It is shown that the proposed method leads to greater guaranteed precision in all control cases discussed.

The solar system: Importance of research to the biological sciences

NASA Technical Reports Server (NTRS)

Klein, Harold P.

1992-01-01

An attempt is made to describe the scope of scientific areas that comprise the current field of exobiology in the United States. From investigations of astrophysical phenomena that deal with the birth of stars and planetary systems to questions of molecular biology involving phylogenetic relationships among organisms, from attempts to simulate the synthesis of biological precursor molecules in the chemistry laboratory to making measurements of the organic constituents of Titan's atmosphere, these researches all converge toward a common objective--answering the question of how life came about in the universe.

Metal-driven and covalent synthesis of supramolecular grids from racks: a convergent approach to heterometallic and heteroleptic nanostructures.

PubMed

Schmittel, Michael; Kalsani, Venkateshwarlu; Bats, Jan W

2005-06-13

Supramolecular nanogrids were prepared from dynamic supramolecular racks through the coupling of terminal alkynes using either a covalent (with CuCl/O(2)) or a coordinative (with [trans-(PEt(3))(2)PtCl(2)]) approach. Because of the rapid equilibration of the racks (as tested by exchange reactions), oligomeric adducts potentially formed in the coupling process will selectively furnish the nanogrids through an entropically driven self-repair mechanism. To ascertain the structural assignment, the nanogrids were also synthesized by an independent strategy.

Nonequilibrium synthesis of NbAl3 and Nb-Al-V alloys by laser cladding. I - Microstructure evolution

NASA Technical Reports Server (NTRS)

Sircar, S.; Chattopadhyay, K.; Mazumder, J.

1992-01-01

The evolution of the microstructure in NbAl3 synthesized by a laser cladding technique (a rapid solidification process, with cooling rates up to 10 exp 6 C/sec) is investigated, and the phases are identified using convergent beam electron diffraction. Two new metastable phases were identified and characterized in detail. The effect of adding V on the final microstructure was also investigated, and the various phase chemistries and the partitioning of different elements into different phases were studied.

Total synthesis of steroids and heterosteroids from BISTRO.

PubMed

Ibrahim-Ouali, Malika

2015-06-01

Due to their high profile biological activity, the steroids are among the most important secondary metabolites. A review of literature on the total synthesis of steroids starting from BISTRO (1,8-bis(trimethylsilyl)-2,6-octadiene) is presented. Copyright © 2015 Elsevier Inc. All rights reserved.

Substituted 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones as novel anti-MRSA agents: synthesis, SAR, and in-vitro assessment.

PubMed

Diwakar, Santosh D; Bhagwat, Sachin S; Shingare, Murlidhar S; Gill, Charansing H

2008-08-15

In search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones 7a-h by convergent synthesis approach. All the synthesized compounds were assayed for their in-vitro antibacterial activities against gram-negative and gram-positive bacteria. The preliminary structure-activity relationship, to elucidate the essential structure requirements for the antimicrobial activity that results into anti-MRSA (methicillin-resistant S. aureus) potential, has been described. Amongst the synthesized compounds 7d, 7e, 7f and 7h were found to possess activity against methicillin-resistant S. aureus in addition to the activity against other bacterial strains such as E. faecalis, S. pneumoniae, and E. coli.

Highly Stereoselective Synthesis of Cyclopentanes bearing Four Stereocenters by a Rhodium Carbene–Initiated Domino Sequence

PubMed Central

Parr, Brendan T.; Davies, Huw M. L.

2014-01-01

Stereoselective synthesis of a cyclopentane nucleus by convergent annulations constitutes a significant challenge for synthetic chemists. Though a number of biologically relevant cyclopentane natural products are known, more often than not, the cyclopentane core is assembled in a stepwise fashion due to lack of efficient annulation strategies. Herein, we report the rhodium-catalyzed reactions of vinyldiazoacetates with (E)-1,3-disubstituted 2-butenols generate cyclopentanes, containing four new stereogenic centers with very high levels of stereoselectivity (99% ee, >97 : 3 dr). The reaction proceeds by a carbene–initiated domino sequence consisting of five distinct steps: rhodium–bound oxonium ylide formation, [2,3]-sigmatropic rearrangement, oxy-Cope rearrangement, enol–keto tautomerization, and finally an intramolecular carbonyl ene reaction. A systematic study is presented detailing how to control chirality transfer in each of the four stereo-defining steps of the cascade, consummating in the development of a highly stereoselective process. PMID:25082301

Improved approximations for control augmented structural synthesis

NASA Technical Reports Server (NTRS)

Thomas, H. L.; Schmit, L. A.

1990-01-01

A methodology for control-augmented structural synthesis is presented for structure-control systems which can be modeled as an assemblage of beam, truss, and nonstructural mass elements augmented by a noncollocated direct output feedback control system. Truss areas, beam cross sectional dimensions, nonstructural masses and rotary inertias, and controller position and velocity gains are treated simultaneously as design variables. The structural mass and a control-system performance index can be minimized simultaneously, with design constraints placed on static stresses and displacements, dynamic harmonic displacements and forces, structural frequencies, and closed-loop eigenvalues and damping ratios. Intermediate design-variable and response-quantity concepts are used to generate new approximations for displacements and actuator forces under harmonic dynamic loads and for system complex eigenvalues. This improves the overall efficiency of the procedure by reducing the number of complete analyses required for convergence. Numerical results which illustrate the effectiveness of the method are given.

Atom-Economical Dimerization Strategy by the Rhodium-Catalyzed Addition of Carboxylic Acids to Allenes: Protecting-Group-Free Synthesis of Clavosolide A and Late-Stage Modification.

PubMed

Haydl, Alexander M; Breit, Bernhard

2015-12-14

Natural products of polyketide origin with a high level of symmetry, in particular C2 -symmetric diolides as a special macrolactone-based product class, often possess a broad spectrum of biological activity. An efficient route to this important structural motif was developed as part of a concise and highly convergent synthesis of clavosolide A. This strategy features an atom-economic "head-to-tail" dimerization by the stereoselective rhodium-catalyzed addition of carboxylic acids to terminal allenes with the simultaneous construction of two new stereocenters. The excellent efficiency and selectivity with which the C2 -symmetric core structures were obtained are remarkable considering the outcome under classical dimerization conditions. Furthermore, this approach facilitates late-stage modification and provides ready access to potential new lead structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Observer synthesis for a class of Takagi-Sugeno descriptor system with unmeasurable premise variable. Application to fault diagnosis

NASA Astrophysics Data System (ADS)

López-Estrada, F. R.; Astorga-Zaragoza, C. M.; Theilliol, D.; Ponsart, J. C.; Valencia-Palomo, G.; Torres, L.

2017-12-01

This paper proposes a methodology to design a Takagi-Sugeno (TS) descriptor observer for a class of TS descriptor systems. Unlike the popular approach that considers measurable premise variables, this paper considers the premise variables depending on unmeasurable vectors, e.g. the system states. This consideration covers a large class of nonlinear systems and represents a real challenge for the observer synthesis. Sufficient conditions to guarantee robustness against the unmeasurable premise variables and asymptotic convergence of the TS descriptor observer are obtained based on the H∞ approach together with the Lyapunov method. As a result, the designing conditions are given in terms of linear matrix inequalities (LMIs). In addition, sensor fault detection and isolation are performed by means of a generalised observer bank. Two numerical experiments, an electrical circuit and a rolling disc system, are presented in order to illustrate the effectiveness of the proposed method.

SETI in the light of cosmic convergent evolution

NASA Astrophysics Data System (ADS)

Flores Martinez, Claudio L.

2014-11-01

Theodosius Dobzhansky, one of the founding fathers of the modern evolutionary synthesis, once famously stated that ;nothing makes sense in biology except in the light of evolution;. Here it will be argued that nothing in astrobiology makes sense except in the light of ;Cosmic Convergent Evolution; (CCE). This view of life contends that natural selection is a universal force of nature that leads to the emergence of similarly adapted life forms in analogous planetary biospheres. Although SETI historically preceded the rise of astrobiology that we have witnessed in the recent decade, one of its main tenets from the beginning was the convergence of life on a cosmic scale toward intelligent behavior and subsequent communication via technological means. The question of cultural convergence in terms of symbolic exchange, language and scientific capabilities between advanced interstellar civilizations has been the subject of ongoing debate. However, at the core of the search for extraterrestrial intelligence lies in essence a biological problem since even post-biological extraterrestrial intelligences must have had an origin based on self-replicating biopolymers. Thus, SETI assumes a propensity of the Universe towards biogenesis in accordance with CCE, a new evolutionary concept which posits the multiple emergence of life across the Cosmos. Consequently, we have to wonder about the biophilic properties the Universe apparently exhibits, as well as to try to find an encompassing theory that is able to explain this ;fine-tuning; in naturalistic terms. The aims of this paper are as follows: 1) to emphasize the importance of convergent evolution in astrobiology and ongoing SETI research; 2) to introduce novel and biology-centered cosmological ideas such as the ;Selfish Biocosm Hypothesis; and the ;Evo Devo Universe; as valuable arguments in theorizing about the origin and nature of extraterrestrial intelligence and 3) to synthesize these findings within an emerging post-biological paradigm on which future SETI efforts may be founded.

Total synthesis of (±)-antroquinonol d.

PubMed

Sulake, Rohidas S; Jiang, Yan-Feng; Lin, Hsiao-Han; Chen, Chinpiao

2014-11-21

Total synthesis of (±)-antroquinonol D, which is isolated from very expensive and rarely found Antrodia camphorata and which has potential anticancer properties, was achieved from 4-methoxyphenol. In addition, a Michael addition to dimethoxy cyclohexadienones was studied. The main step involved chelation and substrate-controlled diastereoselective reduction of cyclohexenone and lactonization. Lactone synthesis facilitated the diastereoselective reduction of ketone, which help control the desired stereochemistry at the crucial stereogenic center in the natural product. Other key reactions in the synthesis involved a Michael addition of dimethyl malonate on cyclohexadienone, dihydroxylation, and Wittig olefination. A sesquiterpene side chain was synthesized through coupling with geranyl phenyl sulfide and Bouveault-Blanc reduction.

Three dimensional investigation of the shock train structure in a convergent-divergent nozzle

NASA Astrophysics Data System (ADS)

Mousavi, Seyed Mahmood; Roohi, Ehsan

2014-12-01

Three-dimensional computational fluid dynamics analyses have been employed to study the compressible and turbulent flow of the shock train in a convergent-divergent nozzle. The primary goal is to determine the behavior, location, and number of shocks. In this context, full multi-grid initialization, Reynolds stress turbulence model (RSM), and the grid adaption techniques in the Fluent software are utilized under the 3D investigation. The results showed that RSM solution matches with the experimental data suitably. The effects of applying heat generation sources and changing inlet flow total temperature have been investigated. Our simulations showed that changes in the heat generation rate and total temperature of the intake flow influence on the starting point of shock, shock strength, minimum pressure, as well as the maximum flow Mach number.

Is there no end to the total syntheses of strychnine? Lessons to be learned for strategy and tactics in total synthesis**

PubMed Central

Cannon, Jeffrey S.; Overman, Larry E.

2013-01-01

From the 19th century to the present, the complex indole alkaloid strychnine has engaged the chemical community. In this review, we examine why strychnine has been and remains today an important target for directed synthesis efforts. A selection of the diverse syntheses of strychnine is discussed with the aim of identifying their influence on the evolution of the strategy and tactics of organic synthesis. PMID:22431197

Efficient total synthesis of (S)-14-azacamptothecin.

PubMed

Liu, Guan-Sai; Yao, Yuan-Shan; Xu, Peng; Wang, Shaozhong; Yao, Zhu-Jun

2010-06-01

An efficient total synthesis of (S)-14-azacamptothecin has been accomplished in 10 steps and 56% overall yield from 5H-pyrano[4,3-d]pyrimidine 8. A mild Hendrickson reagent-triggered intramolecular cascade cyclization, a highly enantioselective dihydroxylation, and an efficient palladium-catalyzed transformation of an O-allyl into N-allyl group are the key steps in the synthesis. This work provides a much higher overall yield than the previous achievement and shows sound flexibility for the further applications that will lead to new bioactive analogues.

Total synthesis of the proposed structure of trichodermatide A.

PubMed

Myers, Eddie; Herrero-Gómez, Elena; Albrecht, Irina; Lachs, Jennifer; Mayer, Peter; Hanni, Matti; Ochsenfeld, Christian; Trauner, Dirk

2014-10-17

A short total synthesis of the published structure of racemic trichodermatide A is reported. Our synthesis involves a Knoevenagel condensation/Michael addition sequence, followed by the formation of tricyclic hexahydroxanthene-dione and a diastereoselective bis-hydroxylation. The final product, the structure of which was confirmed by X-ray crystallography, has NMR spectra that are very similar, but not identical, to those of the isolated natural product. Quantum chemically computed (13)C shifts agree well with the present NMR measurements.

Total Synthesis of the Post-translationally Modified Polyazole Peptide Antibiotic Goadsporin.

PubMed

Dexter, Hannah L; Williams, Huw E L; Lewis, William; Moody, Christopher J

2017-03-06

The structurally unique polyazole antibiotic goadsporin contains six heteroaromatic oxazole and thiazole rings integrated into a linear array of amino acids that also contains two dehydroalanine residues. An efficient total synthesis of goadsporin is reported in which the key steps are the use of rhodium(II)-catalyzed reactions of diazocarbonyl compounds to generate the four oxazole rings, which demonstrates the power of rhodium carbene chemistry in organic chemical synthesis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Total synthesis of nepetoidin B

USDA-ARS?s Scientific Manuscript database

The total synthesis of nepetoidin B (the 2-(3,4-dihydroxyphenyl)ethenyl ester of 3-(3,4-dihydroxy¬phenyl)-2-propenoic acid) has been achieved in two steps from commercially available 1,5-bis(3,4-dimethoxyphenyl)-1,4-pentadien-3-one. Tetramethylated nepetoidin B was prepared directly by Baeyer-Villig...

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

The Pauson-Khand Reaction as a New Entry to the Synthesis of Bridged Bicyclic Heterocycles: Application to the Enantioselective Total Synthesis of (−)-Alstonerine

PubMed Central

Miller, Kenneth A.; Shanahan, Charles S.; Martin, Stephen F.

2008-01-01

The first application of the Pauson-Khand reaction (PKR) to the synthesis of azabridged bicyclic structures is described. Compounds containing azabicyclo[3.3.1]nonane and azabicyclo[3.2.1]octane rings fused to cyclopentenones were efficiently constructed via the PKR of cis-2,6-disubstituted N-acyl piperidine enyne substrates, many of which can be readily prepared from 4-methoxypyridine in a few steps. Moreover, the PKR of cis-2,6-disubstituted piperazine enynes allowed the preparation of diazabicyclo[3.3.1]nonanes fused to cyclopentenones. This new strategy for the synthesis of azabridged bicyclic frameworks was exploited as a key step in a concise, enantioselective total synthesis of the macroline alklaoid (−)-alstonerine. PMID:19122869

The Pauson-Khand Reaction as a New Entry to the Synthesis of Bridged Bicyclic Heterocycles: Application to the Enantioselective Total Synthesis of (-)-Alstonerine.

PubMed

Miller, Kenneth A; Shanahan, Charles S; Martin, Stephen F

2008-01-01

The first application of the Pauson-Khand reaction (PKR) to the synthesis of azabridged bicyclic structures is described. Compounds containing azabicyclo[3.3.1]nonane and azabicyclo[3.2.1]octane rings fused to cyclopentenones were efficiently constructed via the PKR of cis-2,6-disubstituted N-acyl piperidine enyne substrates, many of which can be readily prepared from 4-methoxypyridine in a few steps. Moreover, the PKR of cis-2,6-disubstituted piperazine enynes allowed the preparation of diazabicyclo[3.3.1]nonanes fused to cyclopentenones. This new strategy for the synthesis of azabridged bicyclic frameworks was exploited as a key step in a concise, enantioselective total synthesis of the macroline alklaoid (-)-alstonerine.

Enantioselective synthesis of pactamycin, a complex antitumor antibiotic.

PubMed

Malinowski, Justin T; Sharpe, Robert J; Johnson, Jeffrey S

2013-04-12

Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties across multiple phylogenetic domains, but it is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.

Compact and wide-field-of-view head-mounted display

NASA Astrophysics Data System (ADS)

Uchiyama, Shoichi; Kamakura, Hiroshi; Karasawa, Joji; Sakaguchi, Masafumi; Furihata, Takeshi; Itoh, Yoshitaka

1997-05-01

A compact and wide field of view HMD having 1.32-in full color VGA poly-Si TFT LCDs and simple eyepieces much like LEEP optics has been developed. The total field of view is 80 deg with a 40 deg overlap in its central area. Each optical unit which includes an LCD and eyepiece is 46 mm in diameter and 42 mm in length. The total number of pixels is equivalent to (864 times 3) times 480. This HMD realizes its wide field of view and compact size by having a narrower binocular area (overlap area) than that of commercialized HMDs. For this reason, it is expected that the frequency of monocular vision will be more than that of commercialized HMDs and human natural vision. Therefore, we researched the convergent state of eyes while observing the monocular areas of this HMD by employing an EOG and considered the suitability of this HMD to human vision. As a result, it was found that the convergent state of the monocular vision was nearly equal to that of binocular vision. That is, it can be said that this HMD has the possibility of being well suited to human vision in terms of the convergence.

Night myopia is reduced in binocular vision.

PubMed

Chirre, Emmanuel; Prieto, Pedro M; Schwarz, Christina; Artal, Pablo

2016-06-01

Night myopia, which is a shift in refraction with light level, has been widely studied but still lacks a complete understanding. We used a new infrared open-view binocular Hartmann-Shack wave front sensor to quantify night myopia under monocular and natural binocular viewing conditions. Both eyes' accommodative response, aberrations, pupil diameter, and convergence were simultaneously measured at light levels ranging from photopic to scotopic conditions to total darkness. For monocular vision, reducing the stimulus luminance resulted in a progression of the accommodative state that tends toward the subject's dark focus or tonic accommodation and a change in convergence following the induced accommodative error. Most subjects presented a myopic shift of accommodation that was mitigated in binocular vision. The impact of spherical aberration on the focus shift was relatively small. Our results in monocular conditions support the hypothesis that night myopia has an accommodative origin as the eye progressively changes its accommodation state with decreasing luminance toward its resting state in total darkness. On the other hand, binocularity restrains night myopia, possibly by using fusional convergence as an additional accommodative cue, thus reducing the potential impact of night myopia on vision at low light levels.

Rational design, synthesis and biological screening of triazine-triazolopyrimidine hybrids as multitarget anti-Alzheimer agents.

PubMed

Jameel, Ehtesham; Meena, Poonam; Maqbool, Mudasir; Kumar, Jitendra; Ahmed, Waqar; Mumtazuddin, Syed; Tiwari, Manisha; Hoda, Nasimul; Jayaram, B

2017-08-18

In our endeavor towards the development of potent multitarget ligands for the treatment of Alzheimer's disease, a series of triazine-triazolopyrimidine hybrids were designed, synthesized and characterized by various spectral techniques. Docking and scoring techniques were used to design the inhibitors and to display their interaction with key residues of active site. Organic synthesis relied upon convergent synthetic routes were mono and di-substituted triazines were connected with triazolopyrimidine using piperazine as a linker. In total, seventeen compounds were synthesized in which the di-substituted triazine-triazolopyrimidine derivatives 9a-d showed better acetylcholinesterase (AChE) inhibitory activity than the corresponding tri-substituted triazine-triazolopyrimidine derivatives 10a-f. Out of the disubstituted triazine-triazolopyrimidine based compounds, 9a and 9b showed encouraging inhibitory activity on AChE with IC 50 values 0.065 and 0.092 μM, respectively. Interestingly, 9a and 9b also demonstrated good inhibition selectivity towards AChE over BuChE by ∼28 folds. Furthermore, kinetic analysis and molecular modeling studies showed that 9a and 9b target both catalytic active site as well as peripheral anionic site of AChE. In addition, these derivatives effectively modulated Aβ self-aggregation as investigated through CD spectroscopy, ThT fluorescence assay and electron microscopy. Besides, these compounds exhibited potential antioxidants (2.15 and 2.91 trolox equivalent by ORAC assay) and metal chelating properties. In silico ADMET profiling highlighted that, these novel triazine derivatives have appropriate drug like properties and possess very low toxic effects in the primarily pharmacokinetic study. Overall, the multitarget profile exerted by these novel triazine molecules qualified them as potential anti-Alzheimer drug candidates in AD therapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions.

PubMed

Veronese, Nicola; Solmi, Marco; Luchini, Claudio; Lu, Ru-Band; Stubbs, Brendon; Zaninotto, Leonardo; Correll, Christoph U

2016-06-01

Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD. Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-evidence based synthesis. Out of 214 hits, 12 studies (RCTs=5, other designs=7, total n=422) were included. Donepezil (studies=5; treated=102 vs. placebo=21): there was strong evidence for no effect on mania and psychotic symptoms; low evidence indicating no effect on depression. Galantamine (studies=3; treated=21 vs. controls=20) (placebo=10, healthy subjects=10): there was strong evidence for no effect on mania; moderate evidence for no effect on depression; low evidence for no effect on global functioning. Memantine (studies=4; treated=152 vs. placebo=88): there was conflicting evidence regarding efficacy for mania, depression and global functioning. Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics. There is limited but converging evidence of no effect of AceI in BD, and conflicting evidence about memantine in BD. Too few studies of mostly medium/low quality and lacking sufficient numbers of patients in specific mood states, especially mania, contributed data, focusing solely on short-term/medium-term treatment, necessitating additional high-quality research to yield more definite results. Copyright © 2016 Elsevier B.V. All rights reserved.

Continuum Limit of Total Variation on Point Clouds

NASA Astrophysics Data System (ADS)

García Trillos, Nicolás; Slepčev, Dejan

2016-04-01

We consider point clouds obtained as random samples of a measure on a Euclidean domain. A graph representing the point cloud is obtained by assigning weights to edges based on the distance between the points they connect. Our goal is to develop mathematical tools needed to study the consistency, as the number of available data points increases, of graph-based machine learning algorithms for tasks such as clustering. In particular, we study when the cut capacity, and more generally total variation, on these graphs is a good approximation of the perimeter (total variation) in the continuum setting. We address this question in the setting of Γ-convergence. We obtain almost optimal conditions on the scaling, as the number of points increases, of the size of the neighborhood over which the points are connected by an edge for the Γ-convergence to hold. Taking of the limit is enabled by a transportation based metric which allows us to suitably compare functionals defined on different point clouds.

Convergent close-coupling calculations of positron-magnesium scattering

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

Savage, Jeremy S.; Fursa, Dmitry V.; Bray, Igor

2011-06-15

The single-center convergent close-coupling method has been applied to positron-magnesium scattering at incident energies from 0.01 to 100 eV. Cross sections are presented for elastic scattering and excitation of 3 {sup 1}P, as well as for the total ionization and total scattering processes. We also provide an estimate of the positronium formation cross section. The results agree very well with the measurements of the total cross section by Stein et al. [Nucl. Instrum. Methods Phys. Res. Sect. B 143, 68 (1998)], and consistent with the positronium formation measurements of Surdutovich et al. [Phys. Rev. A 68, 022709 (2003)] for positronmore » energies above the ionization threshold. For energies below the positronium formation threshold (0.8 eV) we find a large P-wave resonance at 0.17 eV. A similar resonance behavior was found by Mitroy and Bromley [Phys. Rev. Lett. 98, 173001 (2007)] at an energy of 0.1 eV.« less

New second order Mumford-Shah model based on Γ-convergence approximation for image processing

NASA Astrophysics Data System (ADS)

Duan, Jinming; Lu, Wenqi; Pan, Zhenkuan; Bai, Li

2016-05-01

In this paper, a second order variational model named the Mumford-Shah total generalized variation (MSTGV) is proposed for simultaneously image denoising and segmentation, which combines the original Γ-convergence approximated Mumford-Shah model with the second order total generalized variation (TGV). For image denoising, the proposed MSTGV can eliminate both the staircase artefact associated with the first order total variation and the edge blurring effect associated with the quadratic H1 regularization or the second order bounded Hessian regularization. For image segmentation, the MSTGV can obtain clear and continuous boundaries of objects in the image. To improve computational efficiency, the implementation of the MSTGV does not directly solve its high order nonlinear partial differential equations and instead exploits the efficient split Bregman algorithm. The algorithm benefits from the fast Fourier transform, analytical generalized soft thresholding equation, and Gauss-Seidel iteration. Extensive experiments are conducted to demonstrate the effectiveness and efficiency of the proposed model.

Convergent validity of actigraphy with polysomnography and parent reports when measuring sleep in children with Down syndrome.

PubMed

Esbensen, A J; Hoffman, E K; Stansberry, E; Shaffer, R

2018-04-01

There is a need for rigorous measures of sleep in children with Down syndrome as sleep is a substantial problem in this population and there are barriers to obtaining the gold standard polysomnography (PSG). PSG is cost-prohibitive when measuring treatment effects in some clinical trials, and children with Down syndrome may not cooperate with undergoing a PSG. Minimal information is available on the validity of alternative methods of assessing sleep in children with Down syndrome, such as actigraphy and parent ratings. Our study examined the concurrent and convergent validity of different measures of sleep, including PSG, actigraphy and parent reports of sleep among children with Down syndrome. A clinic (n = 27) and a community (n = 47) sample of children with Down syndrome were examined. In clinic, children with Down syndrome wore an actigraph watch during a routine PSG. In the community, children with Down syndrome wore an actigraph watch for a week at home at night as part of a larger study on sleep and behaviour. Their parent completed ratings of the child's sleep during that same week. Actigraph watches demonstrated convergent validity with PSG when measuring a child with Down syndrome's total amount of sleep time, total wake time after sleep onset and sleep period efficiency. In contrast, actigraph watches demonstrated poor correlations with parent reports of sleep, and with PSG when measuring the total time in bed and total wake episodes. Actigraphy, PSG and parent ratings of sleep demonstrated poor concurrent validity with clinical diagnosis of obstructive sleep apnoea. Our current data suggest that actigraph watches demonstrate convergent validity and are sensitive to measuring certain sleep constructs (duration, efficiency) in children with Down syndrome. However, parent reports, such as the Children's Sleep Habits Questionnaire, may be measuring other sleep constructs. These findings highlight the importance of selecting measures of sleep related to target concerns. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Protein Synthesis in Mucin-Producing Tissues Is Conserved When Dietary Threonine Is Limiting in Piglets.

PubMed

Munasinghe, Lalani L; Robinson, Jason L; Harding, Scott V; Brunton, Janet A; Bertolo, Robert F

2017-02-01

The neonatal gastrointestinal tract extracts the majority of dietary threonine on the first pass to maintain synthesis of threonine-rich mucins in mucus. As dietary threonine becomes limiting, this extraction must limit protein synthesis in extraintestinal tissues at the expense of maintaining protein synthesis in mucin-producing tissues. The objective was to determine the dietary threonine concentration at which protein synthesis is reduced in various tissues. Twenty Yucatan miniature piglets (10 females; mean ± SD age, 15 ± 1 d; mean ± SD weight, 3.14 ± 0.30 kg) were fed 20 test diets with different threonine concentrations, from 0.5 to 6.0 g/100 g total amino acids (AAs; i.e., 20-220% of requirement), and various tissues were analyzed for protein synthesis by administering a flooding dose of [ 3 H]phenylalanine. The whole-body requirement was determined by [1- 14 C]phenylalanine oxidation and plasma threonine concentrations. Breakpoint analysis indicated a whole-body requirement of 2.8-3.0 g threonine/100 g total AAs. For all of the non-mucin-producing tissues as well as lung and colon, breakpoint analyses indicated decreasing protein synthesis rates below the following concentrations (expressed in g threonine/100 g total AAs; mean ± SE): gastrocnemius muscle, 1.76 ± 0.23; longissimus dorsi muscle, 2.99 ± 0.50; liver, 2.45 ± 0.60; kidney, 3.81 ± 0.97; lung, 1.95 ± 0.14; and colon, 1.36 ± 0.29. Protein synthesis in the other mucin-producing tissues (i.e., stomach, proximal jejunum, midjejunum, and ileum) did not change with decreasing threonine concentrations, but mucin synthesis in the ileum and colon decreased over threonine concentrations <4.54 ± 1.50 and <3.20 ± 4.70 g/100 g total AAs, respectively. The results of this study illustrate that dietary threonine is preferentially used for protein synthesis in gastrointestinal tissues in piglets. If dietary threonine intake is deficient, then muscle growth and the functions of other tissues are likely compromised at the expense of maintenance of the mucus layer in mucin-producing tissues. © 2017 American Society for Nutrition.

WRINKLED1 Rescues Feedback Inhibition of Fatty Acid Synthesis in Hydroxylase-Expressing Seeds1[OPEN

PubMed Central

Browse, John

2016-01-01

Previous attempts at engineering Arabidopsis (Arabidopsis thaliana) to produce seed oils containing hydroxy fatty acids (HFA) have resulted in low yields of HFA compared with the native castor (Ricinus communis) plant and caused undesirable effects, including reduced total oil content. Recent studies have led to an understanding of problems involved in the accumulation of HFA in oils of transgenic plants, which include metabolic bottlenecks and a decrease in the rate of fatty acid synthesis. Focusing on engineering the triacylglycerol assembly mechanisms led to modest increases in the HFA content of seed oil, but much room for improvement still remains. We hypothesized that engineering fatty acid synthesis in the plastids to increase flux would facilitate enhanced total incorporation of fatty acids, including HFA, into seed oil. The transcription factor WRINKLED1 (WRI1) positively regulates the expression of genes involved in fatty acid synthesis and controls seed oil levels. We overexpressed Arabidopsis WRI1 in seeds of a transgenic line expressing the castor fatty acid hydroxylase. The proportion of HFA in the oil, the total HFA per seed, and the total oil content of seeds increased to an average of 20.9%, 1.26 µg, and 32.2%, respectively, across five independent lines, compared with 17.6%, 0.83 µg, and 27.9%, respectively, for isogenic segregants. WRI1 and WRI1-regulated genes involved in fatty acid synthesis were up-regulated, providing for a corresponding increase in the rate of fatty acid synthesis. PMID:27208047

Clinical test responses to different orthoptic exercise regimes in typical young adults.

PubMed

Horwood, Anna; Toor, Sonia

2014-03-01

The relative efficiency of different eye exercise regimes is unclear, and in particular the influences of practice, placebo and the amount of effort required are rarely considered. This study measured conventional clinical measures following different regimes in typical young adults. A total of 156 asymptomatic young adults were directed to carry out eye exercises three times daily for 2 weeks. Exercises were directed at improving blur responses (accommodation), disparity responses (convergence), both in a naturalistic relationship, convergence in excess of accommodation, accommodation in excess of convergence, and a placebo regime. They were compared to two control groups, neither of which were given exercises, but the second of which were asked to make maximum effort during the second testing. Instruction set and participant effort were more effective than many exercises. Convergence exercises independent of accommodation were the most effective treatment, followed by accommodation exercises, and both regimes resulted in changes in both vergence and accommodation test responses. Exercises targeting convergence and accommodation working together were less effective than those where they were separated. Accommodation measures were prone to large instruction/effort effects and monocular accommodation facility was subject to large practice effects. Separating convergence and accommodation exercises seemed more effective than exercising both systems concurrently and suggests that stimulation of accommodation and convergence may act in an additive fashion to aid responses. Instruction/effort effects are large and should be carefully controlled if claims for the efficacy of any exercise regime are to be made. © 2014 The Authors Ophthalmic & Physiological Optics published by John Wiley & Sons Ltd on behalf of The College of Optometrists.

The many roads to parasitism: a tale of convergence.

PubMed

Poulin, Robert

2011-01-01

Parasitic organisms account for a large portion of living species. They have arisen on multiple independent occasions in many phyla, and thus encompass a huge biological diversity. This review uses several lines of evidence to argue that this vast diversity can be reduced to a few evolutionary end points that transcend phylogenetic boundaries. These represent peaks in the adaptive landscape reached independently by different lineages undergoing convergent evolution. Among eukaryotic parasites living in or on animals, six basic parasitic strategies are identified based on the number of hosts used per parasite generation, the fitness loss incurred by the host, and the transmission routes used by the parasites. They are parasitoids, parasitic castrators, directly transmitted parasites, trophically transmitted parasites, vector-transmitted parasites and micropredators. These show evidence of convergence in morphology, physiology, reproduction, life cycles and transmission patterns. Parasite-host body size ratios, and the relationship between virulence and intensity of infection, are also associated with the different parasitic strategies, but not consistently so. At the population level, patterns of parasite distribution among hosts are not uniform across all parasitic strategies, but are distinctly different for parasitoids and castrators than for other parasites. To demonstrate that the above six strategies defined for animal parasites are universal, comparisons are made with parasites of plants, in particular, plant-parasitic nematodes and parasitic angiosperms; these are shown to follow the same evolutionary trajectories seen among animal parasites, despite huge physiological and ecological differences between animals and plants. Beyond demonstrating the inevitable convergence of disparate lineages across biological hyperspace towards a limited set of adaptive strategies, this synthesis also provides a unifying framework for the study of parasitism. Copyright © 2011 Elsevier Ltd. All rights reserved.

Total synthesis and stereochemical assignment of the spiroisoxazoline natural product (+)-calafianin.

PubMed

Bardhan, Sujata; Schmitt, Daniel C; Porco, John A

2006-03-02

Synthesis of the spiroisoxazoline natural product (+)-calafianin is reported using asymmetric nucleophilic epoxidation and nitrile oxide cycloaddition as key steps. Synthesis and spectral analysis of all calafianin stereoisomers led to unambiguous assignment of relative and absolute stereochemistry.

Stereoselective total synthesis of Oxylipin from open chain gluco-configured building block.

PubMed

Borkar, Santosh Ramdas; Aidhen, Indrapal Singh

2017-04-18

Total synthesis of naturally occurring Oxylipin has been achieved from open chain gluco-configured building block which is readily assembled from inexpensive and commercially available D-(+)-gluconolactone. Grignard reaction and Wittig olefination reactions are key steps for the requisite CC bond formation. Copyright © 2017. Published by Elsevier Ltd.

A low-complexity 2-point step size gradient projection method with selective function evaluations for smoothed total variation based CBCT reconstructions

NASA Astrophysics Data System (ADS)

Song, Bongyong; Park, Justin C.; Song, William Y.

2014-11-01

The Barzilai-Borwein (BB) 2-point step size gradient method is receiving attention for accelerating Total Variation (TV) based CBCT reconstructions. In order to become truly viable for clinical applications, however, its convergence property needs to be properly addressed. We propose a novel fast converging gradient projection BB method that requires ‘at most one function evaluation’ in each iterative step. This Selective Function Evaluation method, referred to as GPBB-SFE in this paper, exhibits the desired convergence property when it is combined with a ‘smoothed TV’ or any other differentiable prior. This way, the proposed GPBB-SFE algorithm offers fast and guaranteed convergence to the desired 3DCBCT image with minimal computational complexity. We first applied this algorithm to a Shepp-Logan numerical phantom. We then applied to a CatPhan 600 physical phantom (The Phantom Laboratory, Salem, NY) and a clinically-treated head-and-neck patient, both acquired from the TrueBeam™ system (Varian Medical Systems, Palo Alto, CA). Furthermore, we accelerated the reconstruction by implementing the algorithm on NVIDIA GTX 480 GPU card. We first compared GPBB-SFE with three recently proposed BB-based CBCT reconstruction methods available in the literature using Shepp-Logan numerical phantom with 40 projections. It is found that GPBB-SFE shows either faster convergence speed/time or superior convergence property compared to existing BB-based algorithms. With the CatPhan 600 physical phantom, the GPBB-SFE algorithm requires only 3 function evaluations in 30 iterations and reconstructs the standard, 364-projection FDK reconstruction quality image using only 60 projections. We then applied the algorithm to a clinically-treated head-and-neck patient. It was observed that the GPBB-SFE algorithm requires only 18 function evaluations in 30 iterations. Compared with the FDK algorithm with 364 projections, the GPBB-SFE algorithm produces visibly equivalent quality CBCT image for the head-and-neck patient with only 180 projections, in 131.7 s, further supporting its clinical applicability.

A low-complexity 2-point step size gradient projection method with selective function evaluations for smoothed total variation based CBCT reconstructions.

PubMed

Song, Bongyong; Park, Justin C; Song, William Y

2014-11-07

The Barzilai-Borwein (BB) 2-point step size gradient method is receiving attention for accelerating Total Variation (TV) based CBCT reconstructions. In order to become truly viable for clinical applications, however, its convergence property needs to be properly addressed. We propose a novel fast converging gradient projection BB method that requires 'at most one function evaluation' in each iterative step. This Selective Function Evaluation method, referred to as GPBB-SFE in this paper, exhibits the desired convergence property when it is combined with a 'smoothed TV' or any other differentiable prior. This way, the proposed GPBB-SFE algorithm offers fast and guaranteed convergence to the desired 3DCBCT image with minimal computational complexity. We first applied this algorithm to a Shepp-Logan numerical phantom. We then applied to a CatPhan 600 physical phantom (The Phantom Laboratory, Salem, NY) and a clinically-treated head-and-neck patient, both acquired from the TrueBeam™ system (Varian Medical Systems, Palo Alto, CA). Furthermore, we accelerated the reconstruction by implementing the algorithm on NVIDIA GTX 480 GPU card. We first compared GPBB-SFE with three recently proposed BB-based CBCT reconstruction methods available in the literature using Shepp-Logan numerical phantom with 40 projections. It is found that GPBB-SFE shows either faster convergence speed/time or superior convergence property compared to existing BB-based algorithms. With the CatPhan 600 physical phantom, the GPBB-SFE algorithm requires only 3 function evaluations in 30 iterations and reconstructs the standard, 364-projection FDK reconstruction quality image using only 60 projections. We then applied the algorithm to a clinically-treated head-and-neck patient. It was observed that the GPBB-SFE algorithm requires only 18 function evaluations in 30 iterations. Compared with the FDK algorithm with 364 projections, the GPBB-SFE algorithm produces visibly equivalent quality CBCT image for the head-and-neck patient with only 180 projections, in 131.7 s, further supporting its clinical applicability.

Laser Velocimeter Optical Traverse Scheme: An Investigation of a Proposed Optical Scanning Technique for Arnold Engineering and Development Center’s Four-Foot Transonic Wind Tunnel.

DTIC Science & Technology

1983-12-01

applies not his reason, but his memory....No human investigation can call Itself true science, unless it comes through mathematical demonstration...between laser beam lines and mirror lines • • 18 3.2 Relationship between virtual image and object image for reflection at a plane surface...Results show that for equal indices of refraction inside and out- side the tunnel, the laser beams of a converging pair do not totally converge with its

Convergence of quantum electrodynamics in a curved modification of Minkowski space.

PubMed Central

Segal, I E; Zhou, Z

1994-01-01

The interaction and total hamiltonians for quantum electrodynamics, in the interaction representation, are entirely regular self-adjoint operators in Hilbert space, in the universal covering manifold M of the conformal compactification of Minkowski space Mo. (M is conformally equivalent to the Einstein universe E, in which Mo may be canonically imbedded.) In a fixed Lorentz frame this may be expressed as convergence in a spherical space with suitable periodic boundary conditions in time. The traditional relativistic theory is the formal limit of the present variant as the space curvature vanishes. PMID:11607455

Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization.

PubMed

Ohshima, Takashi; Xu, Youjun; Takita, Ryo; Shimizu, Satoshi; Zhong, Dafang; Shibasaki, Masakatsu

2002-12-11

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.

Total Synthesis of Ionic Liquid Systems for Dissolution of Lunar Simulant

NASA Technical Reports Server (NTRS)

Sharpe, Robert J.; Karr, Laurel J.; Paley, Mark S.

2010-01-01

For purposes of Space Resource Utilization, work in the total synthesis of a new ionic liquid system for the extraction of oxygen and metals from lunar soil is studied and described. Reactions were carried out according to procedures found in the chemical literature, analyzed via Thin-Layer Chromatography and 1H Nuclear Magnetic Resonance Spectroscopy and purified via vacuum distillation and rotary evaporation. Upon final analysis via 1H NMR, it was found that while the intermediates of the synthesis had been achieved, unexpected side products were also present. The mechanisms and constraints of the synthesis are described as well as the final results of the project and recommendations for continued study

Egocentrism in Children: Its Generality and Correlates. Head Start Evaluation and Research Center.

ERIC Educational Resources Information Center

Shantz, Carolyn U.

The construct of egocentrism within Piaget's theory of intellectual development was evaluated as to its convergent, discriminant, and predictive validity within the concrete-operational stage. A total of eighty Negro children drawn from grades one through four in low and middle socioeconomic level schools, were tested individually on a total of…

Time Course of the Response of Myofibrillar and Sarcoplasmic Protein Metabolism to Unweighting of the Soleus Muscle

NASA Technical Reports Server (NTRS)

Munoz, Kathryn A.; Satarug, Soisungwan; Tischler, Marc E.

1993-01-01

Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of H-3-phenylaianine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin.

Control of RNA synthesis in Escherichia coli after a shift to higher temperature.

PubMed Central

Ryals, J; Little, R; Bremer, H

1982-01-01

Parameters of RNA synthesis were measured after a temperature upshift in a pair of Escherichia coli B/r strains that are isogenic except for having relA and relA+ loci, to examine the cause for a reported anomaly in the correlation between guanosine tetraphosphate (ppGpp) and stable RNA (rRNA, tRNA) synthesis under such conditions. Two main results were: (i) the specific stable RNA gene activity (stable RNA per total RNA synthesis) correlated in the conventionally expected fashion with the level of ppGpp but was obscured by a nonspecific increase in the RNA chain elongation rate due to the higher temperature; (ii) the temperature upshift caused a transient reduction in the RNA polymerase activity (transcribing per total enzyme) that accounts for the previously observed oscillating RNA synthesis rate after a temperature shift. PMID:6179925

Prandtl-Meyer flow tables for parahydrogen at total temperatures from 30K to 290K and for nitrogen at total temperatures from 100K to 300K at total pressures from 1 ATM to 10 ATM

NASA Technical Reports Server (NTRS)

Haut, R. C.; Adcock, J. B.

1976-01-01

The dependency of Mach number on the Prandtl-Meyer function was numerically determined by iterating the Prandtl-Meyer function and applying the Muller method to converge on the Mach number for flows in cryogenic parahydrogen and nitrogen at various total pressures and total temperatures. The results are compared with the ideal diatomic gas values and are presented in tabular form.

Synthesis of heterocycles: Indolo (2,1-a) isoquinolines, renewables, and aptamer ligands for cellular imaging

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

Beasley, Jonathan

2013-01-01

In this thesis, we explore both total syntheses and methodologies of several aromatic heterocyclic molecules. Extensions of the Kraus indole synthesis toward 2-substituted and 2,3-disubstituted indoles, as well as biologically attractive indolo[2,1-a]isoquinolines are described. Recent renewable efforts directed to commodity maleic acid and the first reported furan-based ionic liquids are described. Our total synthesis of mRNA aptamer ligand PDC-Gly, and its dye coupled forms, plus aminoglycoside dye coupled ligands used in molecular imaging, are described.

Total Synthesis of Strychnine.

PubMed

Lee, Geun Seok; Namkoong, Gil; Park, Jisook; Chen, David Y-K

2017-11-16

The total synthesis of the flagship Strychnos indole alkaloid, strychnine, has been accomplished. The developed synthetic sequence features a novel vinylogous 1,4-addition, a challenging iodinium salt mediated silyl enol ether arylation, a palladium-catalyzed Heck reaction, and a streamlined late-stage conversion to strychnine. Furthermore, an application of asymmetric counterion-directed catalysis (ACDC) in the context of target-oriented organic synthesis has been rendered access to an optically active material. The synthetic sequence described herein represents the most concise entry to optically active strychnine to date. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Is there no end to the total syntheses of strychnine? Lessons learned in strategy and tactics in total synthesis.

PubMed

Cannon, Jeffrey S; Overman, Larry E

2012-04-27

From the 19th century to the present, the complex indole alkaloid strychnine has engaged the chemical community. In this Review, we examine why strychnine has been and remains today an important target for directed synthesis efforts. A selection of the diverse syntheses of strychnine is discussed with the aim of identifying their influence on the evolution of the strategy and tactics of organic synthesis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Catalytic Enantioselective Total Synthesis of (+)-Liphagal**

PubMed Central

Day, Joshua J.; McFadden, Ryan M.; Virgil, Scott C.; Kolding, Helene; Alleva, Jennifer L.; Stoltz, Brian M.

2012-01-01

Ring a ding: The first catalytic enantioselective total synthesis of the meroterpenoid natural product (+)-liphagal is disclosed. The approach showcases a variety of technology including enantioselective enolate alkylation, a photochemical alkyne-alkene [2+2] reaction, microwave-assisted metal catalysis, and an intramolecular aryne capture cyclization reaction. Pivotal to the successful completion of the synthesis was a sequence involving ring expansion from a [6-5-4] tricycle to a [6-7] bicyclic core followed by stereoselective hydrogenation of a sterically occluded tri-substituted olefin to establish the trans homodecalin system found in the natural product. PMID:21671325

A Concise Synthesis of the Erythrina Alkaloid 3–Demethoxyerythratidinone via Combined Rhodium Catalysis

PubMed Central

Joo, Jung Min; David, Ramoncito A.; Yuan, Yu; Lee, Chulbom

2010-01-01

The total synthesis of the erythrina alkaloid 3–demethoxyerythratidinone has been achieved via a strategy based on combined rhodium catalysis. The catalytic tandem cyclization effected by the interplay of alkynyl and vinylidene rhodium species allows for efficient access to the A and B rings of the tetracyclic erythrinane skeleton in a single step. The synthesis also features rapid preparation of the requisite precursor for the double ring closure and thus has been completed in only 7 total steps in 41% overall yield. PMID:21090648

Recent Advances in the Synthesis of Morphine and Related Alkaloids

NASA Astrophysics Data System (ADS)

Chida, Noritaka

Morphine, an alkaloid isolated from the opium poppy, has been widely used as an analgesic, and has been a fascinating synthetic target of organic chemists. After the first total synthesis reported in 1952, a number of synthetic studies toward morphine have been reported, and findings obtained in such studies have greatly contributed to the progress of synthetic organic chemistry as well as medicinal chemistry. This review provides an overview of recent studies toward the total synthesis of morphine and related alkaloids. Work reported in the literature since 2004 will be reviewed.

LDL-C levels in older people: Cholesterol homeostasis and the free radical theory of ageing converge.

PubMed

Mc Auley, Mark T; Mooney, Kathleen M

2017-07-01

The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations. We hypothesize that the free radical theory of ageing (FRTA) together with disrupted cholesterol homeostasis can account for these observations. Based on this hypothesis, dysregulated hepatic cholesterol homeostasis in older people is characterised by two distinct metabolic states. The first state accounts for an older person who has elevated plasma LDL-C. This state is underpinned by the FRTA which suggests there is a decrease in cellular antioxidant capacity with age. This deficiency enables hepatic reactive oxidative species (ROS) to induce the total activation of HMG-CoA reductase, the key rate limiting enzyme in cholesterol biosynthesis. An increase in cholesterol synthesis elicits a corresponding rise in LDL-C, due to the downregulation of LDL receptor synthesis, and increased production of very low density lipoprotein cholesterol (VLDL-C). In the second state of dysregulation, ROS also trigger the total activation of HMG-CoA reductase. However, due to an age associated decrease in the activity of cholesterol-esterifying enzyme, acyl CoA: cholesterol acyltransferase, there is restricted conversion of excess free cholesterol (FC) to cholesterol esters. Consequently, the secretion of VLDL-C drops, and there is a corresponding decrease in LDL-C. As intracellular levels of FC accumulate, this state progresses to a pathophysiological condition akin to nonalcoholic fatty liver disease. It is our conjecture this deleterious state has the potential to account for the inverse association between LDL-C level and CVD risk observed in older people. Copyright © 2017 Elsevier Ltd. All rights reserved.

Study of alloy disorder in quantum dots through multi-million atom simulations

NASA Technical Reports Server (NTRS)

Kilmeck, Gerhard; Oyafuso, Fabiano; Boykin, T. B.; Bowen, R. C.; von Allmen, Paul A.

2003-01-01

A tight binding model which includes s, p, d, s orbitals is used to examine the electronic structures of an ensemble of dome-shaped In0.6 Ga0.4 As quantum dots. Given ensembles of identically sized quantum dots, variations in composition and configuration yield a linewidth broadening of less than 0.35 meV, much smaller than the total broadening determined from photoluminescence experiments. It is also found that the computed disorder-induced broadening is very sensitive to the applied boundary conditions, so that care must be taken to ensure proper convergence of the numerical results. Examination of local eigenenergies as functions of position shows similar convergence problems and indicates that an inaccurate resolution of the equilibrium atomic positions due to truncation of the simulation domain may be the source of the slow ground state convergence.

Enantioselective Total Synthesis of (−)-Minovincine in Nine Chemical Steps: An Approach to Ketone Activation in Cascade Catalysis

PubMed Central

Laforteza, Brian N.; Pickworth, Mark

2014-01-01

More cycling–fewer steps The first enantioselective total synthesis of (−)-minovincine has been accomplished in nine chemical steps and 13% overall yield. A novel, one-step Diels–Alder/β-elimination/conjugate addition organocascade sequence allowed rapid access to the central tetracyclic core in an asymmetric manner. PMID:24000234

Total Synthesis of Jiadifenolide**

PubMed Central

Paterson, Ian; Xuan, Mengyang; Dalby, Stephen M

2014-01-01

As a potent neurotrophic agent, the sesquiterpenoid jiadifenolide represents a valuable small-molecule lead for the potential therapeutic treatment of neurodegenerative diseases. A stereocontrolled total synthesis of this densely functionalized natural product is reported, central to which is an adventurous samarium-mediated cyclization reaction to establish the tricyclic core and the adjacent C5 and C6 quaternary stereocenters. PMID:24861364

Nazarov cyclization initiated by peracid oxidation: the total synthesis of (+/-)-rocaglamide.

PubMed

Malona, John A; Cariou, Kevin; Frontier, Alison J

2009-06-10

The total syntheses of aglafolin, rocagloic acid, and rocaglamide using Nazarov cyclization are described. Generation of the necessary oxyallyl cation intermediate was accomplished via peracid oxidation of an allenol ether to generate an unusual oxycarbenium ion species that undergoes cyclization. The synthesis is efficient, highly diastereoselective, and strategically distinct from previous syntheses of rocaglamide.

Contemporary Strategies for the Synthesis of Tetrahydropyran Derivatives: Application to Total Synthesis of Neopeltolide, a Marine Macrolide Natural Product

PubMed Central

Fuwa, Haruhiko

2016-01-01

Tetrahydropyrans are structural motifs that are abundantly present in a range of biologically important marine natural products. As such, significant efforts have been paid to the development of efficient and versatile methods for the synthesis of tetrahydropyran derivatives. Neopeltolide, a potent antiproliferative marine natural product, has been an attractive target compound for synthetic chemists because of its complex structure comprised of a 14-membered macrolactone embedded with a tetrahydropyran ring, and twenty total and formal syntheses of this natural product have been reported so far. This review summarizes the total and formal syntheses of neopeltolide and its analogues, highlighting the synthetic strategies exploited for constructing the tetrahydropyran ring. PMID:27023567

Accessibility of selenomethionine proteins by total chemical synthesis: structural studies of human herpesvirus-8 MIP-II.

PubMed

Shao, W; Fernandez, E; Wilken, J; Thompson, D A; Siani, M A; West, J; Lolis, E; Schweitzer, B I

1998-12-11

The determination of high resolution three-dimensional structures by X-ray crystallography or nuclear magnetic resonance (NMR) is a time-consuming process. Here we describe an approach to circumvent the cloning and expression of a recombinant protein as well as screening for heavy atom derivatives. The selenomethionine-modified chemokine macrophage inflammatory protein-II (MIP-II) from human herpesvirus-8 has been produced by total chemical synthesis, crystallized, and characterized by NMR. The protein has a secondary structure typical of other chemokines and forms a monomer in solution. These results indicate that total chemical synthesis can be used to accelerate the determination of three-dimensional structures of new proteins identified in genome programs.

Comparing the nine-item Shared Decision-Making Questionnaire to the OPTION Scale - an attempt to establish convergent validity.

PubMed

Scholl, Isabelle; Kriston, Levente; Dirmaier, Jörg; Härter, Martin

2015-02-01

While there has been a clear move towards shared decision-making (SDM) in the last few years, the measurement of SDM-related constructs remains challenging. There has been a call for further psychometric testing of known scales, especially regarding validity aspects. To test convergent validity of the nine-item Shared Decision-Making Questionnaire (SDM-Q-9) by comparing it to the OPTION Scale. Cross-sectional study. Data were collected in outpatient care practices. Patients suffering from chronic diseases and facing a medical decision were included in the study. Consultations were evaluated using the OPTION Scale. Patients completed the SDM-Q-9 after the consultation. First, the internal consistency of both scales and the inter-rater reliability of the OPTION Scale were calculated. To analyse the convergent validity of the SDM-Q-9, correlation between the patient (SDM-Q-9) and expert ratings (OPTION Scale) was calculated. A total of 21 physicians provided analysable data of consultations with 63 patients. Analyses revealed good internal consistency of the SDM-Q-9 and limited internal consistency of the OPTION Scale. Inter-rater reliability of the latter was less than optimal. Association between the total scores of both instruments was weak with a Spearman correlation of r = 0.19 and did not reach statistical significance. By the use of the OPTION Scale convergent validity of the SDM-Q-9 could not be established. Several possible explanations for this result are discussed. This study shows that the measurement of SDM remains challenging. © 2012 John Wiley & Sons Ltd.

SU-F-BRCD-09: Total Variation (TV) Based Fast Convergent Iterative CBCT Reconstruction with GPU Acceleration.

PubMed

Xu, Q; Yang, D; Tan, J; Anastasio, M

2012-06-01

To improve image quality and reduce imaging dose in CBCT for radiation therapy applications and to realize near real-time image reconstruction based on use of a fast convergence iterative algorithm and acceleration by multi-GPUs. An iterative image reconstruction that sought to minimize a weighted least squares cost function that employed total variation (TV) regularization was employed to mitigate projection data incompleteness and noise. To achieve rapid 3D image reconstruction (< 1 min), a highly optimized multiple-GPU implementation of the algorithm was developed. The convergence rate and reconstruction accuracy were evaluated using a modified 3D Shepp-Logan digital phantom and a Catphan-600 physical phantom. The reconstructed images were compared with the clinical FDK reconstruction results. Digital phantom studies showed that only 15 iterations and 60 iterations are needed to achieve algorithm convergence for 360-view and 60-view cases, respectively. The RMSE was reduced to 10-4 and 10-2, respectively, by using 15 iterations for each case. Our algorithm required 5.4s to complete one iteration for the 60-view case using one Tesla C2075 GPU. The few-view study indicated that our iterative algorithm has great potential to reduce the imaging dose and preserve good image quality. For the physical Catphan studies, the images obtained from the iterative algorithm possessed better spatial resolution and higher SNRs than those obtained from by use of a clinical FDK reconstruction algorithm. We have developed a fast convergence iterative algorithm for CBCT image reconstruction. The developed algorithm yielded images with better spatial resolution and higher SNR than those produced by a commercial FDK tool. In addition, from the few-view study, the iterative algorithm has shown great potential for significantly reducing imaging dose. We expect that the developed reconstruction approach will facilitate applications including IGART and patient daily CBCT-based treatment localization. © 2012 American Association of Physicists in Medicine.

Tropical Hydroclimate Change during Heinrich Stadial 1: An Integrative Proxy-Model Synthesis

NASA Astrophysics Data System (ADS)

Lawman, A. E.; Sun, T.; Shanahan, T. M.; Di Nezio, P. N.; Gomez, K.; Piatrunia, N.; Sun, C.; Wu, X.; Kageyama, M.; Merkel, U.; Otto-Bliesner, B. L.; Abe-Ouchi, A.; Lohmann, G.; Singarayer, J. S.

2017-12-01

We explore the response of tropical climate to abrupt cooling of the North Atlantic (NA) during Heinrich Stadial 1 (HS1) combining paleoclimate proxies with model simulations. A total of 146 published paleoclimate records from tropical locations are used to categorize whether HS1 was wetter, drier, or unchanged relative to a deglacial baseline state. Only records with sufficient resolution to resolve HS1 and sufficient length to characterize the deglacial trend are considered. This synthesis reveals large-scale patterns of hydroclimate change relative to glacial conditions, confirming previously reported weaker Indian summer monsoon, a wetter southern Africa, and drying over the Caribbean. Our synthesis also reveals large-scale drying over the Maritime continent as well as wetter conditions in northern Australia and southern tropical South America. Our reinterpretation of the available proxy data reveals far more complexity and uncertainties for equatorial East Africa, a region that appears to straddle a pattern of dryer conditions to the north and wetter conditions to the south. Overall, these patterns of hydroclimate change depart from a southward shift of the Inter Tropical Convergence Zone (ITCZ), particularly outside the tropical Atlantic. We explore mechanisms driving these changes using a multi-model ensemble of "hosing" simulations performed relative to glacial conditions. The models show robust weakening of the Afro-Asian Monsoon, which we attribute to ventilation of colder mid-latitude air. Not all models simulate the remaining patterns inferred from the proxy data. The best-agreeing models indicate that cooling over the tropical NA and the Caribbean may be essential to communicate the response to the global tropics. This response can induce warming over the tropical South Atlantic via the wind-evaporation-SST feedback, driving wetter conditions in South Africa and tropical South America. Cooling over the Caribbean is communicated to the Pacific over the Central American isthmus resulting in an El Niño-like pattern accompanied by drying over the Maritime Continent - as seen in the proxy data. Together these results show a dominant role for altered tropical SST gradients driving changes in tropical rainfall, and a lesser role for inter-hemispheric shifts in the ITCZ.

Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues.

PubMed

Nicolaou, K C; Chen, Pengxi; Zhu, Shugao; Cai, Quan; Erande, Rohan D; Li, Ruofan; Sun, Hongbao; Pulukuri, Kiran Kumar; Rigol, Stephan; Aujay, Monette; Sandoval, Joseph; Gavrilyuk, Julia

2017-11-01

A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including a drug-resistant line. A novel one-step synthesis of anthraquinones and chloro anthraquinones from simple ketone precursors and phenylselenyl chloride is also described. The reported work, featuring novel chemistry and cascade reactions, has potential applications in cancer therapy, including targeted approaches as in antibody-drug conjugates.

Synthesis of the biologically active natural product cyclodepsipeptides apratoxin A and its analogues.

PubMed

Doi, Takayuki

2014-01-01

This paper describes the synthetic studies conducted on a marine natural product, cyclodepsipeptide apratoxin A. Total synthesis of the oxazoline analogue of apratoxin A was achieved. The conversion of oxazoline to thioamide, as well as thioamide formation from a serine-derived compound, were both unsuccessful. However, thiazoline formation from a cysteine-derived compound led to the total synthesis of apratoxin A. An in vivo study on synthetic apratoxin A revealed that it has potent antitumor activity, but with significant toxicity. Solid-phase synthesis of apratoxin A was accomplished using a preformed thiazoline derivative as a coupling unit. This method was used to synthesize several azido-containing analogues as precursors of molecular probes, and these analogues exhibited potent biological activity.

The new synthesis in moral psychology.

PubMed

Haidt, Jonathan

2007-05-18

People are selfish, yet morally motivated. Morality is universal, yet culturally variable. Such apparent contradictions are dissolving as research from many disciplines converges on a few shared principles, including the importance of moral intuitions, the socially functional (rather than truth-seeking) nature of moral thinking, and the coevolution of moral minds with cultural practices and institutions that create diverse moral communities. I propose a fourth principle to guide future research: Morality is about more than harm and fairness. More research is needed on the collective and religious parts of the moral domain, such as loyalty, authority, and spiritual purity.

Aminomethylation of enals through carbene and acid cooperative catalysis: concise access to β(2)-amino acids.

PubMed

Xu, Jianfeng; Chen, Xingkuan; Wang, Ming; Zheng, Pengcheng; Song, Bao-An; Chi, Yonggui Robin

2015-04-20

A convergent, organocatalytic asymmetric aminomethylation of α,β-unsaturated aldehydes by N-heterocyclic carbene (NHC) and (in situ generated) Brønsted acid cooperative catalysis is disclosed. The catalytically generated conjugated acid from the base plays dual roles in promoting the formation of azolium enolate intermediate, formaldehyde-derived iminium ion (as an electrophilic reactant), and methanol (as a nucleophilic reactant). This redox-neutral strategy is suitable for the scalable synthesis of enantiomerically enriched β(2) -amino acids bearing various substituents. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemoenzymatic synthesis of Amaryllidaceae constituents and biological evaluation of their C-1 analogs. The next generation synthesis of 7-deoxypancratistatin and dihydrolycoricidine.1

PubMed Central

Collins, Jonathan; Rinner, Uwe; Moser, Michael; Hudlicky, Tomas; Ghiviriga, Ion; Romero, Anntherese E.; Kornienko, Alexander; Ma, Dennis; Griffin, Carly; Pandey, Siyaram

2010-01-01

An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds. PMID:20373760

Total synthesis of (+)-antroquinonol and (+)-antroquinonol D.

PubMed

Sulake, Rohidas S; Chen, Chinpiao

2015-03-06

The first total synthesis of (+)-antroquinonol and (+)-antroquinonol D, two structurally unique quinonols with a sesquiterpene side chain, is described. The route features an iridium-catalyzed olefin isomerization-Claisen rearrangement reaction (ICR), lactonization, and Grubbs olefin metathesis. The requisite α,β-unsaturation was achieved via the selenylation/oxidation protocol and elimination of β-methoxy group to provide two natural products from a common intermediate.

Convergent Starvation Signals and Hormone Crosstalk in Regulating Nutrient Mobilization upon Germination in Cereals[C][W

PubMed Central

Hong, Ya-Fang; Ho, Tuan-Hua David; Wu, Chin-Feng; Ho, Shin-Lon; Yeh, Rong-Hwei; Lu, Chung-An; Chen, Peng-Wen; Yu, Lin-Chih; Chao, Annlin; Yu, Su-May

2012-01-01

Germination is a unique developmental transition from metabolically quiescent seed to actively growing seedling that requires an ensemble of hydrolases for coordinated nutrient mobilization to support heterotrophic growth until autotrophic photosynthesis is established. This study reveals two crucial transcription factors, MYBS1 and MYBGA, present in rice (Oryza sativa) and barley (Hordeum vulgare), that function to integrate diverse nutrient starvation and gibberellin (GA) signaling pathways during germination of cereal grains. Sugar represses but sugar starvation induces MYBS1 synthesis and its nuclear translocation. GA antagonizes sugar repression by enhancing conuclear transport of the GA-inducible MYBGA with MYBS1 and the formation of a stable bipartite MYB-DNA complex to activate the α-amylase gene. We further discovered that not only sugar but also nitrogen and phosphate starvation signals converge and interconnect with GA to promote the conuclear import of MYBS1 and MYBGA, resulting in the expression of a large set of GA-inducible but functionally distinct hydrolases, transporters, and regulators associated with mobilization of the full complement of nutrients to support active seedling growth in cereals. PMID:22773748

Iterative divergent/convergent doubling approach to linear conjugated oligomers. A rapid route to a 128 A long potential molecular wire

NASA Astrophysics Data System (ADS)

Tour, James M.; Schumm, Jeffrey S.; Pearson, Darren L.

1994-06-01

Described is the synthesis of oligo (2-ethylphenylene ethynylene)s and oligo (2-(3'ethylheptyl) phenylene ethynylene)s via an iterative divergent convergent approach. Synthesized were the monomer, dimer, tetramer, and octamer of the ethyl derivative and the monomer, dimer, tetramer, octamer, and 16-mer of the ethylheptyl derivative. The 16-mer is 128 A long. At each stage in the iteration, the length of the framework doubles. Only three sets of reaction conditions are needed for the entire iterative synthetic sequence; an iodination, a protodesilylation, and a Pd/Cu-catalyzed cross coupling. The oligomers were characterized spectroscopically and by mass spectrometry. The optical properties are presented which show the stage of optical absorbance saturation. The size exclusion chromatography values for the number average weights, relative to polystyrene, illustrate the tremendous differences in the hydrodynamic volume of these rigid rod oligomers verses the random coils of polystyrene. These differences become quite apparent at the octamer stage. These oligomers may act as molecular wires in molecular electronic devices and they also serve as useful models for understanding related bulk polymers.

Motor competence assessment in children: convergent and discriminant validity between the BOT-2 Short Form and KTK testing batteries.

PubMed

Fransen, Job; D'Hondt, Eva; Bourgois, Jan; Vaeyens, Roel; Philippaerts, Renaat M; Lenoir, Matthieu

2014-06-01

This study investigated convergent and discriminant validity between two motor competence assessment instruments in 2485 Flemish children: the Bruininks-Oseretsky Test of Motor Proficiency 2 Short Form (BOT-2 Short Form) and the KörperKoördinationsTest für Kinder (KTK). A Pearson correlation assessed the relationship between BOT-2 Short Form total, gross and fine motor composite scores and KTK Motor Quotient in three age cohorts (6-7, 8-9, 10-11 years). Crosstabs were used to measure agreement in classification in children scoring below percentile 5 and 15 and above percentile 85 and 95. Moderately strong positive (r=0.44-0.64) associations between BOT-2 total and gross motor composite scores and KTK Motor Quotient and weak positive correlations between BOT-2 Short Form fine motor composite and KTK Motor Quotient scores (r=0.25-0.37) were found. Levels of agreement were fair to moderate. Therefore, some proof of convergent and discriminant validity between BOT-2 Short Form and KTK was established in this study, underlining the notion that the evaluation of motor competence should not be based upon a single assessment instrument. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimal solutions for a bio mathematical model for the evolution of smoking habit

NASA Astrophysics Data System (ADS)

Sikander, Waseem; Khan, Umar; Ahmed, Naveed; Mohyud-Din, Syed Tauseef

In this study, we apply Variation of Parameter Method (VPM) coupled with an auxiliary parameter to obtain the approximate solutions for the epidemic model for the evolution of smoking habit in a constant population. Convergence of the developed algorithm, namely VPM with an auxiliary parameter is studied. Furthermore, a simple way is considered for obtaining an optimal value of auxiliary parameter via minimizing the total residual error over the domain of problem. Comparison of the obtained results with standard VPM shows that an auxiliary parameter is very feasible and reliable in controlling the convergence of approximate solutions.

A unified convergence theory of a numerical method, and applications to the replenishment policies.

PubMed

Mi, Xiang-jiang; Wang, Xing-hua

2004-01-01

In determining the replenishment policy for an inventory system, some researchers advocated that the iterative method of Newton could be applied to the derivative of the total cost function in order to get the optimal solution. But this approach requires calculation of the second derivative of the function. Avoiding this complex computation we use another iterative method presented by the second author. One of the goals of this paper is to present a unified convergence theory of this method. Then we give a numerical example to show the application of our theory.

Investigation of Perforated Convergent-divergent Diffusers with Initial Boundary Layer

NASA Technical Reports Server (NTRS)

Weinstein, Maynard I

1950-01-01

An experimental investigation was made at Mach number 1.90 of the performance of a series of perforated convergent-divergent supersonic diffusers operating with initial boundary layer, which was induced and controlled by lengths of cylindrical inlets affixed to the diffusers. Supercritical mass-flow and peak total-pressure recoveries were decreased slightly by use of the longest inlets (4 inlet diameters in length). Combinations of cylindrical inlets, perforated diffusers, and subsonic diffuser were evaluated as simulated wind tunnels having second throats. Comparisons with noncontracted configurations of similar scale indicated conservatively computed power reductions of 25 percent.

The total occlusal convergence of the abutment of a partial fixed dental prosthesis: A definition and a clinical technique for its assessment

PubMed Central

Mamoun, John S.

2013-01-01

The abutment(s) of a partial fixed dental prosthesis (PFDP) should have a minimal total occlusal convergence (TOC), also called a taper, in order to ensure adequate retention of a PFDP that will be made for the abutment(s), given the height of the abutment(s). This article reviews the concept of PFDP abutment TOC and presents an alternative definition of what TOC is, defining it as the extent to which the shape of an abutment differs from an ideal cylinder shape of an abutment. This article also reviews experimental results concerning what is the ideal TOC in degrees and explores clinical techniques of estimating the TOC of a crown abutment. The author suggests that Dentists use high magnification loupes (×6-8 magnification or greater) or a surgical operating microscope when preparing crown abutments, to facilitate creating a minimum abutment TOC. PMID:24932130

CCC calculated integrated cross sections of electron-H2 scattering

NASA Astrophysics Data System (ADS)

Zammit, Mark; Fursa, Dmitry; Savage, Jeremy; Bray, Igor

2016-09-01

Recently we applied the molecular convergent close-coupling (CCC) method to electron scattering from molecular hydrogen H2. Convergence of the major integrated cross sections has been explicitly demonstrated in the fixed-nuclei approximation by increasing the number of H2 target states in the close-coupling expansion from 9 to 491. The calculations have been performed using a projectile partial wave expansion with maximum orbital angular momentum Lmax = 8 and total orbital angular momentum projections | M | <= 8 . Coupling to the ionization continuum is modeled via a large pseudo state expansion, which we found is required to obtain reliable elastic and excitation cross sections. Here we present benchmark elastic, single-ionization, electronic excitation and total integrated cross sections over a broad energy range (0.1 to 300 eV) and compare with available experiment and previous calculations. Los Alamos National Laboratory and Curtin University.

Convergence or divergence of male and female physicians' hours of work and income.

PubMed

Dedobbeleer, N; Contandriopoulos, A P; Desjardins, S

1995-08-01

This article verifies if the increase in the percentage of women in the medical profession led to the convergence of male and female physicians' hours of work as well as income. Active physicians in Quebec in 1978 were compared to the ones in 1988. Data were obtained from the computerized files of the Quebec Corporation of Physicians and the Régie d'assurance-maladie du Quebec. Despite the increasing representation of women in the medical profession, gender differences in hours worked and income remained. However, results also showed a tendency toward a convergence in total hours of work, more behavioral variation among women physicians and some behavioral change among men. The experience of the past should thus not be used as the basis for projections of future physician productivity or for medical manpower planning purposes without a careful analysis of trends in behavioral changes.

High-Performance AC Power Source by Applying Robust Stability Control Technology for Precision Material Machining

NASA Astrophysics Data System (ADS)

Chang, En-Chih

2018-02-01

This paper presents a high-performance AC power source by applying robust stability control technology for precision material machining (PMM). The proposed technology associates the benefits of finite-time convergent sliding function (FTCSF) and firefly optimization algorithm (FOA). The FTCSF maintains the robustness of conventional sliding mode, and simultaneously speeds up the convergence speed of the system state. Unfortunately, when a highly nonlinear loading is applied, the chatter will occur. The chatter results in high total harmonic distortion (THD) output voltage of AC power source, and even deteriorates the stability of PMM. The FOA is therefore used to remove the chatter, and the FTCSF still preserves finite system-state convergence time. By combining FTCSF with FOA, the AC power source of PMM can yield good steady-state and transient performance. Experimental results are performed in support of the proposed technology.

Convergence of the Graph Allen-Cahn Scheme

NASA Astrophysics Data System (ADS)

Luo, Xiyang; Bertozzi, Andrea L.

2017-05-01

The graph Laplacian and the graph cut problem are closely related to Markov random fields, and have many applications in clustering and image segmentation. The diffuse interface model is widely used for modeling in material science, and can also be used as a proxy to total variation minimization. In Bertozzi and Flenner (Multiscale Model Simul 10(3):1090-1118, 2012), an algorithm was developed to generalize the diffuse interface model to graphs to solve the graph cut problem. This work analyzes the conditions for the graph diffuse interface algorithm to converge. Using techniques from numerical PDE and convex optimization, monotonicity in function value and convergence under an a posteriori condition are shown for a class of schemes under a graph-independent stepsize condition. We also generalize our results to incorporate spectral truncation, a common technique used to save computation cost, and also to the case of multiclass classification. Various numerical experiments are done to compare theoretical results with practical performance.

A totally phosphine-free synthesis of metal telluride nanocrystals by employing alkylamides to replace alkylphosphines for preparing highly reactive tellurium precursors.

PubMed

Yao, Dong; Liu, Yi; Zhao, Wujun; Wei, Haotong; Luo, Xintao; Wu, Zhennan; Dong, Chunwei; Zhang, Hao; Yang, Bai

2013-10-21

Despite the developments in the wet chemical synthesis of high-quality semiconductor nanocrystals (NCs) with diverse elemental compositions, telluride NCs are still irreplaceable materials owing to their excellent photovoltaic and thermoelectric performances. Herein we demonstrate the dissolution of elemental tellurium (Te) in a series of alkylamides by sodium borohydride (NaBH4) reduction at relatively low temperature to produce highly reactive precursors for hot-injection synthesis of telluride NCs. The capability to tune the reactivity of Te precursors by selecting injection temperature permits control of NC size over a broad range. The current preparation of Te precursors is simple, economical, and totally phosphine-free, which will promote the commercial synthesis and applications of telluride NCs.

Liquid gallium columns sheathed with carbon: Bulk synthesis and manipulation.

PubMed

Zhan, Jinhua; Bando, Yoshio; Hu, Junqing; Golberg, Dmitri; Nakanishi, Haruyuki

2005-06-16

It is impossible to fabricate isolated gallium nanomaterials due to the low melting point of Ga (29.8 degrees C) and its high reactivity. We report the bulk synthesis of uniform liquid Ga columns encapsulated into carbon nanotubes through high-temperature chemical reaction between Ga and CH4. The diameter of filled Ga liquid columns is approximately 25 nm, and their length is up to several micrometers. The thickness of the carbon sheaths is approximately 6 nm. Simultaneous condensation of a Ga vapor and carbon clusters results in the generation of Ga-filled carbon nanotubes. A convergent 300 kV electron beam generated in a field emission high-resolution electron microscope is demonstrated to be a powerful tool for delicate manipulation of the liquid Ga nanocolumns: they can be gently joined, cut, and sealed within carbon nanotubes. The self-organization of a carbon sheath during the electron-beam irradiation is discussed. The electron-beam irradiation may also become a decent tool for Ga-filled carbon nanotube thermometer calibration.

Design and Synthesis of Potent Quillaja Saponin Vaccine Adjuvants

PubMed Central

Adams, Michelle M.; Damani, Payal; Perl, Nicholas R.; Won, Annie; Hong, Feng

2010-01-01

The success of antitumor and antiviral vaccines often requires the use of an adjuvant, a substance that significantly enhances the immune response to a co-administered antigen. Only a handful of adjuvants have both sufficient potency and acceptable toxicity for clinical investigation. One promising adjuvant is QS-21, a saponin natural product that is the immunopotentiator of choice in many cancer and infectious disease vaccine clinical trials. However, the therapeutic promise of QS-21 adjuvant is curtailed by several factors, including its scarcity, difficulty in purification to homogeneity, dose-limiting toxicity, and chemical instability. Here we report the design, synthesis, and evaluation of chemically stable synthetic saponins. These novel, amide-modified, non-natural substances exhibit immunopotentiating effects in vivo that rival or exceed that of QS-21 in evaluations with the GD3-KLH melanoma conjugate vaccine. The highly convergent synthetic preparation of these novel saponins establishes new avenues for discovering improved molecular adjuvants for specifically tailored vaccine therapies. PMID:20088518

Green Synthesis of Metallic Nanoparticles via Biological Entities

PubMed Central

Shah, Monaliben; Fawcett, Derek; Sharma, Shashi; Tripathy, Suraj Kumar; Poinern, Gérrard Eddy Jai

2015-01-01

Nanotechnology is the creation, manipulation and use of materials at the nanometre size scale (1 to 100 nm). At this size scale there are significant differences in many material properties that are normally not seen in the same materials at larger scales. Although nanoscale materials can be produced using a variety of traditional physical and chemical processes, it is now possible to biologically synthesize materials via environment-friendly green chemistry based techniques. In recent years, the convergence between nanotechnology and biology has created the new field of nanobiotechnology that incorporates the use of biological entities such as actinomycetes algae, bacteria, fungi, viruses, yeasts, and plants in a number of biochemical and biophysical processes. The biological synthesis via nanobiotechnology processes have a significant potential to boost nanoparticles production without the use of harsh, toxic, and expensive chemicals commonly used in conventional physical and chemical processes. The aim of this review is to provide an overview of recent trends in synthesizing nanoparticles via biological entities and their potential applications. PMID:28793638

The nucleolus—guardian of cellular homeostasis and genome integrity.

PubMed

Grummt, Ingrid

2013-12-01

All organisms sense and respond to conditions that stress their homeostasis by downregulating the synthesis of rRNA and ribosome biogenesis, thus designating the nucleolus as the central hub in coordinating the cellular stress response. One of the most intriguing roles of the nucleolus, long regarded as a mere ribosome-producing factory, is its participation in monitoring cellular stress signals and transmitting them to the RNA polymerase I (Pol I) transcription machinery. As rRNA synthesis is a most energy-consuming process, switching off transcription of rRNA genes is an effective way of saving the energy required to maintain cellular homeostasis during acute stress. The Pol I transcription machinery is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production which, in turn, guides cell growth and proliferation. This review focuses on the mechanisms that link cell physiology to rDNA silencing, a prerequisite for nucleolar integrity and cell survival.

A convergent approach to biocompatible polyglycerol "click" dendrons for the synthesis of modular core-shell architectures and their transport behavior.

PubMed

Wyszogrodzka, Monika; Haag, Rainer

2008-01-01

Dendrimers are an important class of polymeric materials for a broad range of applications in which monodispersity and multivalency are of interest. Here we report on a highly efficient synthetic route towards bifunctional polyglycerol dendrons on a multigram scale. Commercially available triglycerol (1), which is highly biocompatible, was used as starting material. By applying Williamson ether synthesis followed by an ozonolysis/reduction procedure, glycerol-based dendrons up to the fourth generation were prepared. The obtained products have a reactive core, which was further functionalized to the corresponding monoazido derivatives. By applying copper(I)-catalyzed 1,3-dipolar cycloaddition, so-called "click" coupling, a library of core-shell architectures was prepared. After removal of the 1,2-diol protecting groups, water-soluble core-shell architectures 24-27 of different generations were obtained in high yields. In the structure-transport relationship with Nile red we observe a clear dependence on core size and generation of the polyglycerol dendrons.

Lower crust exhumation and ongoing continental convergence in the Variscan Maures-Tanneron Massif, France, geological synthesis and numerical models

NASA Astrophysics Data System (ADS)

Gerbault, Muriel; Schneider, Julie; Corsini, Michel; Reverso-Peila, Alexandre

2015-04-01

The Maures-Tanneron Massif together with Corsica and Sardinia compose the present day southeastern part of the Variscan belt. Pressure-temperature-time patterns were compiled to adress how rocks once forming a thick orogenic crust were exhumed, from burial conditions of ca. 10 kb and ca. 800°C. A continuous evolution from subduction to collision, from ca. 420 Ma to 290 Ma has recently been proposed by Schneider et al., 2014, ending with orthogonal Permean rifting. Here we complement this study by exploring the thermo-mechanical conditions prevailing during the massive exhumation of this orogenic crust. Based on field observations and petrological analysis indicative of the acceleration of partial melting during ongoing convergence, our numerical models test a scenario in which pre-thickened units located at 40-60 km depth, would have molten due to internal heating and burrial, and were progressively exhumed by gravitationally-driven instabilities to the surface, within ~15-25 Myrs. Assuming temperature dependent elasto-visco-plastic behavior, we have tested rheological layering including mafic or felsic units, far-field convergence and surface processes, as well as temperature-dependent melting conditions and density and viscosity evolution. In order to reproduce asymmetrical exhumation over the given time-scales and over an extent area of more than 50 km synchroneous with the development of compressional folds in the upper crust, a best fit was obtained for an applied far-field convergence of 0.5 cm/yr, equivalent to present day Alpine convergence rates, and a bulk crustal viscosity of at least 102° Pa.s. Crustal heat source had to contribute significantly, whereas a too shallow mantle heat source triggers exceedingly warm and fast exhumation. We propose that the evolution from transpressional to tensile conditions perpendicular to the orogenic axis (north-south Permean rifting versus East-West vergence of the orogenic structures), occurred progressively as internal volume forces rose and exceeded far-field boundary forces, linked with the balancing of masses in all three directions. The original location of this portion of the Variscan belt remains unclear but it presents consistent transitional characteristics between the Massif Central and the Bohemian massif.

Effect of supplementing orchardgrass herbage with a total mixed ration or flaxseed fermentation profile and bacterial protein synthesis in continuous culture

USDA-ARS?s Scientific Manuscript database

A 4-unit dual-flow continuous culture fermentor system was used to evaluate the effects of herbage, a total mixed ration (TMR) and flaxseed on nutrient digestibility and microbial N synthesis. Treatments were randomly assigned to fermentors in a 4 x 4 Latin square design. Each fermentor was fed a to...

Total chemical synthesis and X-ray structure of kaliotoxin by racemic protein crystallography.

PubMed

Pentelute, Brad L; Mandal, Kalyaneswar; Gates, Zachary P; Sawaya, Michael R; Yeates, Todd O; Kent, Stephen B H

2010-11-21

Here we report the total synthesis of kaliotoxin by 'one pot' native chemical ligation of three synthetic peptides. A racemic mixture of D- and L-kaliotoxin synthetic protein molecules gave crystals in the centrosymmetric space group P1 that diffracted to atomic-resolution (0.95 Å), enabling the X-ray structure of kaliotoxin to be determined by direct methods.

Total synthesis of Ivorenolide A following a base-induced elimination protocol.

PubMed

Mohapatra, Debendra K; Umamaheshwar, Gonela; Rao, R Nageshwar; Rao, T Srinivasa; R, Sudheer Kumar; Yadav, Jhillu S

2015-02-20

A concise and stereocontrolled first total synthesis of Ivorenolide A (1) is reported in 16 longest linear steps with a 13.4% overall yield starting from (+)-diethyl tartrate (DET). Key features are base-induced elimination protocol for the construction of chiral propargyl alcohols in both fragments, Pd-catalyzed cross-coupling of terminal acetylenes, and Shiina's 2-methyl-6-nitrobezoic anhydride (MNBA) mediated macrolactonization.

A Safer and Convenient Synthesis of Sulfathiazole for Undergraduate Organic and Medicinal Chemistry Classes

ERIC Educational Resources Information Center

Boyle, Jeff; Otty, Sandra; Sarojini, Vijayalekshmi

2012-01-01

A safer method for the synthesis of the sulfonamide drug sulfathiazole, for undergraduate classes, is described. This method improves upon procedures currently followed in several undergraduate teaching laboratories for the synthesis of sulfathiazole. Key features of this procedure include the total exclusion of pyridine, which has potential…

Change in convergence and accommodation after two weeks of eye exercises in typical young adults

PubMed Central

Horwood, Anna M.; Toor, Sonia S.; Riddell, Patricia M.

2014-01-01

Background Although eye exercises appear to help heterophoria, convergence insufficiency, and intermittent strabismus, results can be confounded by placebo, practice, and encouragement effects. This study assessed objective changes in vergence and accommodation responses in naive young adults after a 2-week period of eye exercises under controlled conditions to determine the extent to which treatment effects occur over other factors. Methods Asymptomatic young adults were randomly assigned to one of two no-treatment (control) groups or to one of six eye exercise groups: accommodation, vergence, both, convergence in excess of accommodation, accommodation in excess of convergence, and placebo. Subjects were tested and retested under identical conditions, except for the second control group, who were additionally encouraged. Objective accommodation and vergence were assessed to a range of targets moving in depth containing combinations of blur, disparity, and proximity/looming cues. Results A total of 156 subjects were included. Response gain improved more for less naturalistic targets where more improvement was possible. Convergence exercises improved vergence for near across all targets (P = 0.035). Mean accommodation changed similarly but nonsignificantly. No other treatment group differed significantly from the nonencouraged control group, whereas encouraging effort produced significantly increased vergence (P = 0.004) and accommodation (P = 0.005) gains in the second control group. Conclusions True treatment effects were small, significantly better only after vergence exercises to a nonaccommodative target, and rarely related to the response they were designed to improve. Exercising accommodation without convergence made no difference to accommodation to cues containing detail. Additional effort improved objective responses the most. PMID:24582466

Intercrop movement of convergent lady beetle, Hippodamia convergens (Coleoptera: Coccinellidae), between adjacent cotton and alfalfa.

PubMed

Bastola, Anup; Parajulee, Megha N; Porter, R Patrick; Shrestha, Ram B; Chen, Fa-Jun; Carroll, Stanley C

2016-02-01

A 2-year study was conducted to characterize the intercrop movement of convergent lady beetle, Hippodamia convergens Guerin-Meneville (Coleoptera: Coccinellidae) between adjacent cotton and alfalfa. A dual protein-marking method was used to assess the intercrop movement of the lady beetles in each crop. In turns field collected lady beetles in each crop were assayed by protein specific ELISA to quantify the movement of beetles between the crops. Results indicated that a high percentage of convergent lady beetles caught in cotton (46% in 2008; 56% in 2009) and alfalfa (46% in 2008; 71% in 2009) contained a protein mark, thus indicating that convergent lady beetle movement was largely bidirectional between the adjacent crops. Although at a much lower proportion, lady beetles also showed unidirectional movement from cotton to alfalfa (5% in 2008 and 6% in 2009) and from alfalfa to cotton (9% in 2008 and 14% in 2009). The season-long bidirectional movement exhibited by the beetles was significantly higher in alfalfa than cotton during both years of the study. The total influx of lady beetles (bidirectional and unidirectional combined) was significantly higher in alfalfa compared with that in cotton for both years. While convergent lady beetles moved between adjacent cotton and alfalfa, they were more attracted to alfalfa when cotton was not flowering and/or when alfalfa offered more opportunities for prey. This study offers much needed information on intercrop movement of the convergent lady beetle that should facilitate integrated pest management decisions in cotton utilizing conservation biological control. © 2014 Institute of Zoology, Chinese Academy of Sciences.

NUMERICAL CONVERGENCE IN SMOOTHED PARTICLE HYDRODYNAMICS

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

Zhu, Qirong; Li, Yuexing; Hernquist, Lars

2015-02-10

We study the convergence properties of smoothed particle hydrodynamics (SPH) using numerical tests and simple analytic considerations. Our analysis shows that formal numerical convergence is possible in SPH only in the joint limit N → ∞, h → 0, and N{sub nb} → ∞, where N is the total number of particles, h is the smoothing length, and N{sub nb} is the number of neighbor particles within the smoothing volume used to compute smoothed estimates. Previous work has generally assumed that the conditions N → ∞ and h → 0 are sufficient to achieve convergence, while holding N{sub nb} fixed.more » We demonstrate that if N{sub nb} is held fixed as the resolution is increased, there will be a residual source of error that does not vanish as N → ∞ and h → 0. Formal numerical convergence in SPH is possible only if N{sub nb} is increased systematically as the resolution is improved. Using analytic arguments, we derive an optimal compromise scaling for N{sub nb} by requiring that this source of error balance that present in the smoothing procedure. For typical choices of the smoothing kernel, we find N{sub nb} ∝N {sup 0.5}. This means that if SPH is to be used as a numerically convergent method, the required computational cost does not scale with particle number as O(N), but rather as O(N {sup 1} {sup +} {sup δ}), where δ ≈ 0.5, with a weak dependence on the form of the smoothing kernel.« less

Ongoing compression triggered exhumation of the orogenic crust in the Variscan Maures-Tanneron Massif, France - Geological arguments and thermo-mechanical tests

NASA Astrophysics Data System (ADS)

Gerbault, Muriel; Schneider, Julie; Reverso-Peila, Alexandre; Corsini, Michel

2016-04-01

The Maures-Tanneron Massif (MTM), together with Corsica and Sardinia, hosted the South-Eastern Variscan belt and record a continuous evolution from continental collision to exhumation. We present a synthesis of the available geological and geochronogical data that explores the transition from convergence to perpendicular Permean extension in the MTM (at ~ 325 Ma ± 25 My). The migmatitic Internal Zone that composes the Western MTM displays structural clues such as backthrusting and magmatic foliations, and metamorphic data indicating exhumation of deep seated partially molten rocks at an apparent heating rate of 1-2 °C/km/My from ca. 345 Ma to 320 Ma. This suggests vertical advective heat transport during continued N140° convergence (D2 phase). In contrast at the same time, the low grade External zone composing the Eastern part of the MTM recorded exhumation of more conductive patterns at an apparent rate of 0.3-0.6 °C/km/My. It is only from ca. 320 Ma that transcurrent motion dominates in the Internal zone and progressively leaves way to N-S strecthing (D3 phase), indicative of orogenic collapse and extension and in asociation with emplacement of larger volumes of magmatism in the crust. Thermo-mechanical modeling complements this synthesis in order to highlight the conditions under which deep seated HP units could melt and massively start to exhume during maintained convergence (phase D2). Accounting for temperature dependent elasto-visco-plastic rheologies, our models explore the dynamics of an orogenic prism starting from a dis-equilibrated state just after slab break-off or delamination, at ca. 350 Ma. We simulate the development of gravitational instabilities in partially melting crust, a process that is already well known to depend on strain-rate, heat sources and strength layering. In order to reproduce the exhumation patterns of rocks from ~50 km depth over the appropriate time-scale (>20 My) and spatial extent (>100 km), a best fit was obtained with a mean convergence rate of 0.5 cm/yr and no exceptional surface processes. Internal heating has a crucial effect and mostly resulted from the radiogenic decay of stacked felsic crustal units. However alternation with mafic units is also necessary in order to prevent lateral spreading of the orogeny. A low viscosity partially molten (eg. felsic) crust also permits mechanical decoupling of surface deformation from the deeper mantle domains, thus reducing the differences due to either a shallow asthenosphere or a competent mantle lithosphere under the orogeny. A shallow asthenosphere produces too warm and fast exhumation. The bulk viscosity of the partially molten orogenic crust controls the timing of exhumation, pointing to the need for further constraints to link the behaviour at different scales of partially molten crust. The MTM witnesses the typical competition between far-field plate convergence and internal body forces, and we plead for a subsequent progressive evolution of transpression to perpendicular extension (still to be tackled with 3D modeling).

Bilateral synergistic convergence associated with homozygous ROB03 mutation (p.Pro771Leu).

PubMed

Khan, Arif O; Oystreck, Darren T; Al-Tassan, Nada; Al-Sharif, Latifa; Bosley, Thomas M

2008-12-01

To document the phenotype and determine the genotype of a child with synergistic convergence. Interventional case report. Patient and nuclear family (7 members total). Ophthalmologic, neurologic, and radiologic examination of the proband; venous blood sampling for candidate gene testing of the proband; venous blood sampling for confirmatory testing in other family members. Clinical and radiologic observations in proband and candidate gene results. The proband, a 9-year-old girl, substituted convergence for horizontal gaze (synergistic convergence) since birth. She also had conjugate pendular nystagmus, asynchronous blinking, and high myopia. No family member had ophthalmologic or medical symptoms. Neuroradiologic imaging revealed hindbrain dysplasia and modest scoliosis. Sequencing of ROB03, the gene associated with horizontal gaze palsy and progressive scoliosis, revealed a novel missense mutation (p.Pro771Leu) that altered an evolutionarily conserved amino acid. Screening the family for this mutation confirmed that both parents were carriers and identified 2 sisters as carriers and 2 brothers as noncarriers. This is the second reported patient with synergistic convergence and the first associated with a documented pathologic genotype. Unlike the previously reported case (which occurred in the setting of the cranial dysinnervation disorder congenital fibrosis of the extraocular muscles), our patient presumably has a supranuclear cause. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Application of the FUN3D Unstructured-Grid Navier-Stokes Solver to the 4th AIAA Drag Prediction Workshop Cases

NASA Technical Reports Server (NTRS)

Lee-Rausch, Elizabeth M.; Hammond, Dana P.; Nielsen, Eric J.; Pirzadeh, S. Z.; Rumsey, Christopher L.

2010-01-01

FUN3D Navier-Stokes solutions were computed for the 4th AIAA Drag Prediction Workshop grid convergence study, downwash study, and Reynolds number study on a set of node-based mixed-element grids. All of the baseline tetrahedral grids were generated with the VGRID (developmental) advancing-layer and advancing-front grid generation software package following the gridding guidelines developed for the workshop. With maximum grid sizes exceeding 100 million nodes, the grid convergence study was particularly challenging for the node-based unstructured grid generators and flow solvers. At the time of the workshop, the super-fine grid with 105 million nodes and 600 million elements was the largest grid known to have been generated using VGRID. FUN3D Version 11.0 has a completely new pre- and post-processing paradigm that has been incorporated directly into the solver and functions entirely in a parallel, distributed memory environment. This feature allowed for practical pre-processing and solution times on the largest unstructured-grid size requested for the workshop. For the constant-lift grid convergence case, the convergence of total drag is approximately second-order on the finest three grids. The variation in total drag between the finest two grids is only 2 counts. At the finest grid levels, only small variations in wing and tail pressure distributions are seen with grid refinement. Similarly, a small wing side-of-body separation also shows little variation at the finest grid levels. Overall, the FUN3D results compare well with the structured-grid code CFL3D. The FUN3D downwash study and Reynolds number study results compare well with the range of results shown in the workshop presentations.

Validation of the Social Appearance Anxiety Scale in Patients with Systemic Sclerosis: A Scleroderma Patient-centered Intervention Network Cohort Study.

PubMed

Mills, Sarah D; Kwakkenbos, Linda; Carrier, Marie-Eve; Gholizadeh, Shadi; Fox, Rina S; Jewett, Lisa R; Gottesman, Karen; Roesch, Scott C; Thombs, Brett D; Malcarne, Vanessa L

2018-01-17

Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes. Patients enrolled in the Scleroderma Patient-centered Intervention Network Cohort completed the SAAS and measures of appearance-related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple-group CFA was used to determine if SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size. A total of 938 patients with SSc were included. CFA supported a one-factor structure (CFI: .92; SRMR: .04; RMSEA: .08), and multiple-group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = .96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression. The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Nonlinearity Analysis for Efficient Modelling of Long-Term CO2 Storage

NASA Astrophysics Data System (ADS)

Li, Boxiao; Benson, Sally; Tchelepi, Hamdi

2014-05-01

Numerical simulation is widely used to predict the long-term fate of the injected CO2 in a storage formation. Performing large-scale simulations is often limited by the computational speed, where convergence failure of Newton iterations is one of the main bottlenecks. In order to design better numerical schemes and faster nonlinear solvers for modelling long-term CO2 storage, the nonlinearity in the simulations has to be analysed thoroughly, and the cause of convergence failures has to be identified clearly. We focus on the transport of CO2 and water in the presence of viscous, gravity, and heterogeneous capillary forces. We investigate the nonlinearity of the discrete transport equation obtained from finite-volume discretization with single-point phase-based upstream weighting, which is the industry standard. In particular, we study the discretized flux expressed as a function of saturations at the upstream and downstream (with respect to the total velocity) of each gridblock interface. We analyse the locations and complexity of the unit-flux, zero-flux, and inflection lines on the numerical flux. The unit- and zero-flux lines, referred to as kinks, correspond to a change of the flow direction, which often occurs when strong buoyancy and capillarity are present. We observe that these kinks and inflection lines are major sources of nonlinear convergence difficulties. We find that kinks create more challenges than inflection lines, especially when their locations depend on both the upstream and downstream saturations of the total velocity. When the flow is driven by viscous and gravity forces (e.g., during CO2 injection), one kink will occur in the numerical flux and its location depends only on the upstream saturation. However, when capillarity is dominant (e.g., during the post-injection period), two kinks will occur and both are functions of the upstream and downstream saturations, causing severe convergence difficulties particularly when heterogeneity is present. Our analysis of the numerical flux theoretically describes the cause of the convergence failures for simulating long-term CO2 storage. This understanding provides useful guidance in designing numerical schemes and nonlinear solvers that overcome the convergence bottlenecks. For example, to reduce the nonlinearity introduced by the two kinks in the presence of capillarity, we modify the method of Cances (2009) to discretize the capillary flux. Consequently, only one kink will occur even for coupled viscous, buoyancy, and heterogeneous capillary forces, and the kink depends only on the upstream saturation of the total velocity. An efficient nonlinear solver that is a significant refinement of the works of Jenny et al. (2009) and Wang and Tchelepi (2013) has also been proposed and demonstrated. References [1] C. Cances. Finite volume scheme for two-phase flows in heterogeneous porous media involving capillary pressure discontinuities. ESAIM:M2AN., 43, 973-1001, (2009). [2] P. Jenny, H.A. Tchelepi, and S.H. Lee. Unconditionally convergent nonlinear solver for hyperbolic conservation laws with S-shaped flux functions. J. Comput. Phys., 228, 7497-7512, (2009). [3] X. Wang and H.A. Tchelepi. Trust-region based solver for nonlinear transport in heterogeneous porous media. J. Comput. Phys., 253, 114-137, (2013).

Structure elucidation of nigricanoside A through enantioselective total synthesis† †Electronic supplementary information (ESI) available: Complete experimental details and characterization data. See DOI: 10.1039/c5sc00281h Click here for additional data file.

PubMed Central

Chen, Jie; Koswatta, Panduka; DeBergh, J. Robb; Fu, Peng; Pan, Ende

2015-01-01

Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity. PMID:26877863

Advances on Semisynthesis, Total Synthesis, and Structure-Activity Relationships of Honokiol and Magnolol Derivatives.

PubMed

Yang, Chun; Zhi, Xiaoyan; Xu, Hui

2016-01-01

Honokiol and magnolol (an isomer of honokiol) are small-molecule polyphenols isolated from the barks of Magnolia officinalis, which have been widely used in traditional Chinese and Japanese medicines. In the last decade, a variety of biological properties of honokiol and magnolol (e.g., anti-oxidativity, antitumor activity, anti-depressant activity, anti-inflammatory activity, neuroprotective activity, anti-diabetic activity, antiviral activity, and antimicrobial activity) have been reported. Meanwhile, certain mechanisms of action of some biological activities were also investigated. Moreover, many analogs of honokiol and magnolol were prepared by structural modification or total synthesis, and some exhibited very potent pharmacological activities with improved water solubility. Therefore, the present review will provide a systematic coverage on recent developments of honokiol and magnolol derivatives in regard to semisynthesis, total synthesis, and structure-activity relationships from 2000 up to now.

Studies of a Diazo Cyclopropanation Strategy for the Total Synthesis of (-)-Lundurine A.

PubMed

Huang, Hong-Xiu; Jin, Shuai-Jiang; Gong, Jin; Zhang, Dan; Song, Hao; Qin, Yong

2015-09-14

The bioactive Kopsia alkaloids lundurines A-D are the only natural products known to contain indolylcyclopropane. Achieving their syntheses can provide important insights into their biogenesis, as well as novel synthetic routes for complex natural products. Asymmetric total synthesis of (-)-lundurine A has previously been achieved through a Simmons-Smith cyclopropanation strategy. Here, the total synthesis of (-)-lundurine A was carried out using a metal-catalyzed diazo cyclopropanation strategy. In order to avoid a carbene CH insertion side reaction during cyclopropanation of α-diazo- carboxylates or cyanides, a one-pot, copper-catalyzed Bamford-Stevens diazotization/diazo decomposition/cyclopropanation cascade was developed, involving hydrazone. This approach simultaneously generates the C/D/E ring system and the two chiral quaternary centers at C2 and C7. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peloruside B, a Potent Antitumor Macrolide from the New Zealand Marine Sponge Mycale hentscheli: Isolation, Structure, Total Synthesis and Bioactivity

PubMed Central

Singh, A. Jonathan; Xu, Chun-Xiao; Xu, Xiaoming; West, Lyndon M.; Wilmes, Anja; Chan, Ariane; Hamel, Ernest; Miller, John H.; Northcote, Peter T.; Ghosh, Arun K.

2009-01-01

Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G2M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization and selective methylation. PMID:19957922

Total synthesis of agalloside, isolated from Aquilaria agallocha, by the 5-O-glycosylation of flavan.

PubMed

Arai, Midori A; Yamaguchi, Yumi; Ishibashi, Masami

2017-06-14

Agalloside (1) is a neural stem cell differentiation activator isolated from Aquilaria agallocha by our group using Hes1 immobilized beads. We conducted the first total synthesis of agalloside (1) via the 5-O-glycosylation of flavan 25 using glycosyl fluoride 20 in the presence of BF 3 ·Et 2 O. Subsequent oxidation with DDQ to flavanone 2 and deprotection successively provided agalloside (1). This synthetic strategy holds promise for use in the synthesis of 5-O-glycosylated flavonoids. The synthesized agalloside (1) accelerated neural stem cell differentiation, which is a result comparable to that for the naturally occurring compound 1.

Nonlinear multivariable design by total synthesis. [of gas turbine engine control systems

NASA Technical Reports Server (NTRS)

Sain, M. K.; Peczkowski, J. L.

1982-01-01

The Nominal Design Problem (NDP) is extended to nonlinear cases, and a new case study of robust feedback synthesis for gas turbine control design is presented. The discussion of NDP extends and builds on earlier Total Synthesis Problem theory and ideas. Some mathematical preliminaries are given in which a bijection from a set S onto a set T is considered, with T admitting the structure of an F-vector space. NDP is then discussed for a nonlinear plant, and nonlinear nominal design is defined and characterized. The design of local controllers for a turbojet and the scheduling of these controls into a global control are addressed.

Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition of 1-yne/ene-vinylcyclopropanes and CO: homologous Pauson-Khand reaction and total synthesis of (+/-)-alpha-agarofuran.

PubMed

Jiao, Lei; Lin, Mu; Zhuo, Lian-Gang; Yu, Zhi-Xiang

2010-06-04

A novel Rh(I)-catalyzed [(3 + 2) + 1] cycloaddition, which can be regarded as a homologous Pauson-Khand reaction, was developed to synthesize bicyclic cyclohexenones and cyclohexanones, enabling a new approach for synthesis of six-membered carbocycles ubiquitously found in natural products and pharmaceutics. The significance of the Rh-catalyzed [(3 + 2) + 1] cycloaddition has been demonstrated by the total synthesis of a furanoid sesquiterpene natural product, alpha-agarofuran, in which the bicyclic skeleton was constructed by the [(3 + 2) + 1] reaction of 1-yne-VCP and CO.

Using a genetic algorithm to abbreviate the Psychopathic Personality Inventory-Revised (PPI-R).

PubMed

Eisenbarth, Hedwig; Lilienfeld, Scott O; Yarkoni, Tal

2015-03-01

Some self-report measures of personality and personality disorders, including the widely used Psychopathic Personality Inventory-Revised (PPI-R), are lengthy and time-intensive. In recent work, we introduced an automated genetic algorithm (GA)-based method for abbreviating psychometric measures. In Study 1, we used this approach to generate a short (40-item) version of the PPI-R using 3 large-N German student samples (total N = 1,590). The abbreviated measure displayed high convergent correlations with the original PPI-R, and outperformed an alternative measure constructed using a conventional approach. Study 2 tested the convergent and discriminant validity of this short version in a fourth student sample (N = 206) using sensation-seeking and sensitivity to reward and punishment scales, again demonstrating similar convergent and discriminant validity for the PPI-R-40 compared with the full version. In a fifth community sample of North American participants acquired using Amazon Mechanical Turk, the PPI-R-40 showed similarly high convergent correlations, demonstrating stability across language, culture, and data-collection method. Taken together, these studies suggest that the GA approach is a viable method for abbreviating measures of psychopathy, and perhaps personality measures in general. 2015 APA, all rights reserved

Global convergence of inexact Newton methods for transonic flow

NASA Technical Reports Server (NTRS)

Young, David P.; Melvin, Robin G.; Bieterman, Michael B.; Johnson, Forrester T.; Samant, Satish S.

1990-01-01

In computational fluid dynamics, nonlinear differential equations are essential to represent important effects such as shock waves in transonic flow. Discretized versions of these nonlinear equations are solved using iterative methods. In this paper an inexact Newton method using the GMRES algorithm of Saad and Schultz is examined in the context of the full potential equation of aerodynamics. In this setting, reliable and efficient convergence of Newton methods is difficult to achieve. A poor initial solution guess often leads to divergence or very slow convergence. This paper examines several possible solutions to these problems, including a standard local damping strategy for Newton's method and two continuation methods, one of which utilizes interpolation from a coarse grid solution to obtain the initial guess on a finer grid. It is shown that the continuation methods can be used to augment the local damping strategy to achieve convergence for difficult transonic flow problems. These include simple wings with shock waves as well as problems involving engine power effects. These latter cases are modeled using the assumption that each exhaust plume is isentropic but has a different total pressure and/or temperature than the freestream.

The use of meta-analysis or research synthesis to combine driving simulation or naturalistic study results on driver distraction.

PubMed

Caird, Jeff K; Johnston, Katherine A; Willness, Chelsea R; Asbridge, Mark

2014-06-01

Three important and inter-related topics are addressed in this paper. First, the importance of meta-analysis and research synthesis methods to combine studies on traffic safety, in general, and on driver distraction, in particular, is briefly reviewed. Second, naturalistic, epidemiologic, and driving simulation studies on driver distraction are used to illustrate convergent and divergent results that have accumulated thus far in this domain of research. In particular, mobile phone conversation, passenger presence, and text messaging naturalistic studies use meta-analyses and research syntheses to illustrate important patterns of results that are in need of more in-depth study. Third, a number of driver distraction study limitations such as poorly defined dependent variables, lack of methodological detail, and omission of statistical information prevent the integration of many studies into meta-analyses. In addition, the overall quality of road safety studies suffers from these same limitations and suggestions for improvement are made to guide researchers and reviewers. Practical Applications. The use of research synthesis and meta-analysis provide comprehensive estimates of the impact of distractions on driving performance, which can be used to guide public policy and future research. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Limits of the Learning Organization: A Critical Look.

ERIC Educational Resources Information Center

Fenwick, Tara J.

The development of the "learning organization" may be traced to three converging trends: the tradition of organizational development; economic shifts to globalization, deregulation, and information-based industry; and total quality management. Learning organizations are generally characterized as follows: organizations that create…

Optimization of gefitinib analogues with potent anticancer activity.

PubMed

Yin, Kai-Hao; Hsieh, Yi-Han; Sulake, Rohidas S; Wang, Su-Pei; Chao, Jui-I; Chen, Chinpiao

2014-11-15

The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Medical libraries, bioinformatics, and networked information: a coming convergence?

PubMed

Lynch, C

1999-10-01

Libraries will be changed by technological and social developments that are fueled by information technology, bioinformatics, and networked information. Libraries in highly focused settings such as the health sciences are at a pivotal point in their development as the synthesis of historically diverse and independent information sources transforms health care institutions. Boundaries are breaking down between published literature and research data, between research databases and clinical patient data, and between consumer health information and professional literature. This paper focuses on the dynamics that are occurring with networked information sources and the roles that libraries will need to play in the world of medical informatics in the early twenty-first century.

Preparation of a Corannulene-functionalized Hexahelicene by Copper(I)-catalyzed Alkyne-azide Cycloaddition of Nonplanar Polyaromatic Units.

PubMed

Álvarez, Celedonio M; Barbero, Héctor; Ferrero, Sergio

2016-09-18

The main purpose of this video is to show 6 reaction steps of a convergent synthesis and prepare a complex molecule containing up to three nonplanar polyaromatic units, which are two corannulene moieties and a racemic hexahelicene linking them. The compound described in this work is a good host for fullerenes. Several common organic reactions, such as free-radical reactions, C-C coupling or click chemistry, are employed demonstrating the versatility of functionalization that this compound can accept. All of these reactions work for planar aromatic molecules. With subtle modifications, it is possible to achieve similar results for nonplanar polyaromatic compounds.

Central mechanisms of odour object perception

PubMed Central

Gottfried, Jay A.

2013-01-01

The stimulus complexity of naturally occurring odours presents unique challenges for central nervous systems that are aiming to internalize the external olfactory landscape. One mechanism by which the brain encodes perceptual representations of behaviourally relevant smells is through the synthesis of different olfactory inputs into a unified perceptual experience — an odour object. Recent evidence indicates that the identification, categorization and discrimination of olfactory stimuli rely on the formation and modulation of odour objects in the piriform cortex. Convergent findings from human and rodent models suggest that distributed piriform ensemble patterns of olfactory qualities and categories are crucial for maintaining the perceptual constancy of ecologically inconstant stimuli. PMID:20700142

Total Radiosynthesis: Thinking outside "the box".

PubMed

Liang, Steven H; Vasdev, Neil

2015-09-01

The logic of total synthesis transformed a stagnant state of medicinal and synthetic organic chemistry when there was a paucity of methods and reagents to synthesize drug molecules and/or natural products. Molecular imaging by positron emission tomography (PET) is now experiencing a renaissance in the way radiopharmaceuticals for molecular imaging are synthesized, however, a paradigm shift is desperately needed in the discovery pipeline to accelerate in vivo imaging studies. A significant challenge in radiochemistry is the limited choice of labeled reagents (or building blocks) available for the synthesis of novel radiopharmaceuticals with the most commonly used short-lived radionuclides carbon-11 ( 11 C; half-life ~20 minutes) and fluorine-18 ( 18 F; half-life ~2 hours). In fact, most drugs cannot be labeled with 11 C or 18 F due to a lack of efficient and diverse radiosynthetic methods. In general, routine radiopharmaceutical production relies on the incorporation of the isotope at the last or penultimate step of synthesis, ideally within one half-life of the radionuclide, to maximize radiochemical yields and specific activities thereby reducing losses due to radioactive decay. Reliance on radiochemistry conducted within the constraints of an automated synthesis unit ("box") has stifled the exploration of multi-step reactions with short-lived radionuclides. Radiopharmaceutical synthesis can be transformed by considering logic of total synthesis to develop novel approaches for 11 C- and 18 F-radiolabeling complex molecules via retrosynthetic analysis and multi-step reactions. As a result of such exploration, new methods, reagents and radiopharmaceuticals for in vivo imaging studies are discovered. A new avenue to develop radiotracers that were previously unattainable due to the lack of efficient radiosynthetic methods is necessary to work towards our ultimate, albeit impossible goal - the concept we term total radiosynthesis - to radiolabel virtually any molecule. As with the vast majority of drugs, most radiotracers also fail, therefore expeditious evaluation of tracers in preclinical models prior to optimization or derivatization of the lead molecules/drugs is necessary. Furthermore the exact position of the 11 C and 18 F radionuclide in tracers is often critical for metabolic considerations, and flexible methodologies to introduce the radiolabel are needed. Using the principles of total synthesis our laboratory and others have shown that multi-step radiochemical reactions are indeed suitable for preclinical and even clinical use. As the goal of total synthesis is to be concise, we have also simplified the syntheses of radiopharmaceuticals. We are presently developing new strategies via [ 11 C]CO 2 fixation which has enabled library radiosynthesis as well as labeling non-activated arenes using [ 18 F]fluoride via iodonium ylides. Both of which have proven to be suitable for human PET imaging. We concurrently utilize state-of-the-art automation technologies including microfluidic flow chemistry and rapid purification strategies for radiopharmaceutical production. In this account we highlight how total radiosynthesis has impacted our radiochemistry program, with prominent examples from others, focusing on its impact towards preclinical and clinical research studies.

Total Radiosynthesis: Thinking outside “the box”

PubMed Central

Liang, Steven H.; Vasdev, Neil

2016-01-01

The logic of total synthesis transformed a stagnant state of medicinal and synthetic organic chemistry when there was a paucity of methods and reagents to synthesize drug molecules and/or natural products. Molecular imaging by positron emission tomography (PET) is now experiencing a renaissance in the way radiopharmaceuticals for molecular imaging are synthesized, however, a paradigm shift is desperately needed in the discovery pipeline to accelerate in vivo imaging studies. A significant challenge in radiochemistry is the limited choice of labeled reagents (or building blocks) available for the synthesis of novel radiopharmaceuticals with the most commonly used short-lived radionuclides carbon-11 (11C; half-life ~20 minutes) and fluorine-18 (18F; half-life ~2 hours). In fact, most drugs cannot be labeled with 11C or 18F due to a lack of efficient and diverse radiosynthetic methods. In general, routine radiopharmaceutical production relies on the incorporation of the isotope at the last or penultimate step of synthesis, ideally within one half-life of the radionuclide, to maximize radiochemical yields and specific activities thereby reducing losses due to radioactive decay. Reliance on radiochemistry conducted within the constraints of an automated synthesis unit (“box”) has stifled the exploration of multi-step reactions with short-lived radionuclides. Radiopharmaceutical synthesis can be transformed by considering logic of total synthesis to develop novel approaches for 11C- and 18F-radiolabeling complex molecules via retrosynthetic analysis and multi-step reactions. As a result of such exploration, new methods, reagents and radiopharmaceuticals for in vivo imaging studies are discovered. A new avenue to develop radiotracers that were previously unattainable due to the lack of efficient radiosynthetic methods is necessary to work towards our ultimate, albeit impossible goal – the concept we term total radiosynthesis - to radiolabel virtually any molecule. As with the vast majority of drugs, most radiotracers also fail, therefore expeditious evaluation of tracers in preclinical models prior to optimization or derivatization of the lead molecules/drugs is necessary. Furthermore the exact position of the 11C and 18F radionuclide in tracers is often critical for metabolic considerations, and flexible methodologies to introduce the radiolabel are needed. Using the principles of total synthesis our laboratory and others have shown that multi-step radiochemical reactions are indeed suitable for preclinical and even clinical use. As the goal of total synthesis is to be concise, we have also simplified the syntheses of radiopharmaceuticals. We are presently developing new strategies via [11C]CO2 fixation which has enabled library radiosynthesis as well as labeling non-activated arenes using [18F]fluoride via iodonium ylides. Both of which have proven to be suitable for human PET imaging. We concurrently utilize state-of-the-art automation technologies including microfluidic flow chemistry and rapid purification strategies for radiopharmaceutical production. In this account we highlight how total radiosynthesis has impacted our radiochemistry program, with prominent examples from others, focusing on its impact towards preclinical and clinical research studies. PMID:27512156

Dynamically accumulated dose and 4D accumulated dose for moving tumors

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

Li Heng; Li Yupeng; Zhang Xiaodong

2012-12-15

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose difference between the dynamic dose and 4D dose as a function of number of deliveries and/or total deliver time was also established.« less

Investigation of installation effects of single-engine convergent-divergent nozzles

NASA Technical Reports Server (NTRS)

Burley, J. R., II; Berrier, B. L.

1982-01-01

An investigation was conducted in the Langley 16-Foot Transonic Tunnel to determine installation effects on single-engine convergent-divergent nozzles applicable to reduced-power supersonic cruise aircraft. Tests were conducted at Mach numbers from 0.50 to 1.20, at angles of attack from -3 degrees to 9 degrees, and at nozzle pressure ratios from 1.0 (jet off) to 8.0. The effects of empennage arrangement, nozzle length, a cusp fairing, and afterbody closure on total aft-end drag coefficient and component drag coefficients were investigated. Basic lift- and drag-coefficient data and external static-pressure distributions on the nozzle and afterbody are presented and discussed.

From Atomistic Model to the Peierls-Nabarro Model with {γ} -surface for Dislocations

NASA Astrophysics Data System (ADS)

Luo, Tao; Ming, Pingbing; Xiang, Yang

2018-05-01

The Peierls-Nabarro (PN) model for dislocations is a hybrid model that incorporates the atomistic information of the dislocation core structure into the continuum theory. In this paper, we study the convergence from a full atomistic model to the PN model with {γ} -surface for the dislocation in a bilayer system. We prove that the displacement field and the total energy of the dislocation solution of the PN model are asymptotically close to those of the full atomistic model. Our work can be considered as a generalization of the analysis of the convergence from atomistic model to Cauchy-Born rule for crystals without defects.

Efficient Simulation of Explicitly Solvated Proteins in the Well-Tempered Ensemble.

PubMed

Deighan, Michael; Bonomi, Massimiliano; Pfaendtner, Jim

2012-07-10

Herein, we report significant reduction in the cost of combined parallel tempering and metadynamics simulations (PTMetaD). The efficiency boost is achieved using the recently proposed well-tempered ensemble (WTE) algorithm. We studied the convergence of PTMetaD-WTE conformational sampling and free energy reconstruction of an explicitly solvated 20-residue tryptophan-cage protein (trp-cage). A set of PTMetaD-WTE simulations was compared to a corresponding standard PTMetaD simulation. The properties of PTMetaD-WTE and the convergence of the calculations were compared. The roles of the number of replicas, total simulation time, and adjustable WTE parameter γ were studied.

Part 1. Synthetic approaches to indole/imidazole marine alkaloids. Part 2. 1-cyanobenzotriazole as a cyanating agent. Part 3. Synthesis of potential molecular rectifiers

NASA Astrophysics Data System (ADS)

Hughes, Terry Vincent

1999-12-01

This dissertation consists of four chapters. The first chapter details the progress toward a total synthesis of securine A (1). Securine A is an indole/imidazole containing marine alkaloid which contains a 2,3-disubstituted indole ring and a 4,5- disubstituted imidazole ring with a 12-membered lactam connecting the two. The approach into the securine A ring system utilized the opening of a pyrano[3,4-b]indol-3-one ring system with a modified histamine derivative. Efforts in the synthesis of securine A were not successful, but the synthesis of a similar analogue, compound 53, which contained a 13-membered ring was achieved. Chapter two deals with the total synthesis of the indole/maleimide/imidazole containing marine alkaloids: the didemnimides A-D (84- 87). The total syntheses of didemnimide A-D were successful and utilized a base catalyzed condensation reaction of methyl indolyl-3-glyoxylate (102) and 1-trityl-4-imidazoleacetamide (104). Chapter three details a new and convenient synthesis of 1-cyanobenzotriazole (123) and efforts to use it as a source of +CN in carbon-carbon forming reactions. The synthesis is safer than previously reported methods and allows for 123 to be made in multi-gram scale rather inexpensively. It was demonstrated that 1-cyanobenzotriazole (123) is a good source of +CN in carbon-carbon forming reactions by reacting with a variety of sp3, Sp 2, and sp carbanions. Chapter four details a new synthesis of hexadecylquinolinium tricyanoquinodimethanide (171) which has been shown to be a molecular rectifier. In search of additional molecular rectifiers, this new methodology was applied to the synthesis of Z- β-(N-n -hexadecyl-2-benzothiazolium)-α-cyano-4-styryldicyanomethanide (181) as well as its selenium and tellurium analogues 190 and 200; respectively. Additionally, the synthesis of other T- D+-π-A- types of molecules was explored in search for other molecular rectifiers. However, of all the compounds synthesized herein, only 171 has been shown to rectify.

Synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates: formal total synthesis of (+)-calystegine b(2).

PubMed

Marco-Contelles, José; de Opazo, Elsa

2002-05-31

The free radical cyclization (FR) and the ring-closing metathesis (RCM) reaction have been analyzed in order to develop new and original synthetic protocols for the synthesis of enantiomerically pure, highly functionalized, medium-sized carbocycles from carbohydrates. As a result, we report here for the first time examples of the 7-exo FR cyclization of acyclic radical precursors derived from sugars. This process appears to be extremely sensitive to the conformational mobility of the radical species in the transition state. The use of two isopropylidene groups blocking four of the total present hydroxyl groups and a good radical acceptor (as an alpha,beta-unsaturated ester) are mandatory conditions for a successful ring closure protocol. The RCM reaction by using Grubbs' catalyst on selected carbohydrate-derived precursors has afforded variable yields of the expected unsaturated cycloheptane or cycloctane derivatives. The synthesis of the cycloheptitols has been carried out in good yields, regardless of the absolute configuration at the different stereocenters and the nature of the O-functional groups bound in allylic positions to one of the double bonds implicated in the metathesis reaction. Conversely, in the cyclooctane synthesis, we have observed that the success of the reaction depends not only on the absolute configuration at the different stereocenters close to the double bonds but also on the nature of the O-protecting groups on these stereocenters. Finally, the RCM strategy has been used in an attempt to prepare natural (+)-calystegine B(2) from D-glucose. The synthesis of compound 92 from D-glucose constitutes a formal total synthesis of (+)-calystegine B(2), showing the importance of the steric hindrance in allylic positions for a successful RCM reaction.

More than anticipated - production of antibiotics and other secondary metabolites by Bacillus amyloliquefaciens FZB42.

PubMed

Chen, Xiao-Hua; Koumoutsi, Alexandra; Scholz, Romy; Borriss, Rainer

2009-01-01

The genome of environmental Bacillus amyloliquefaciens FZB42 harbors numerous gene clusters involved in synthesis of antifungal and antibacterial acting secondary metabolites. Five gene clusters, srf, bmy, fen, nrs, dhb, covering altogether 137 kb, direct non-ribosomal synthesis of the cyclic lipopeptides surfactin, bacillomycin, fengycin, an unknown peptide, and the iron siderophore bacillibactin. Bacillomycin and fengycin were shown to act against phytopathogenic fungi in a synergistic manner. Three gene clusters, mln, bae, and dif, with a total length of 199 kb were shown to direct synthesis of the antibacterial acting polyketides macrolactin, bacillaene, and difficidin. Both, non-ribosomal synthesis of cyclic lipopeptides and synthesis of polyketides are dependent on the presence of a functional sfp gene product, 4'-phosphopantetheinyl transferase, as evidenced by knockout mutation of the sfp gene resulting in complete absence of all those eight compounds. In addition, here we present evidence that a gene cluster encoding enzymes involved in synthesis and export of the antibacterial acting dipeptide bacilysin is also functional in FZB42. In summary, environmental FZB42 devoted about 340 kb, corresponding to 8.5% of its total genetic capacity, to synthesis of secondary metabolites useful to cope with other competing microorganisms present in the plant rhizosphere. Copyright (c) 2008 S. Karger AG, Basel.

Convergent evolution of reduced energy demands in extremophile fish

PubMed Central

Arias-Rodriguez, Lenin; Tobler, Michael

2017-01-01

Convergent evolution in organismal function can arise from nonconvergent changes in traits that contribute to that function. Theory predicts that low resource availability and high maintenance costs in extreme environments select for reductions in organismal energy demands, which could be attained through modifications of body size or metabolic rate. We tested for convergence in energy demands and underlying traits by investigating livebearing fish (genus Poecilia) that have repeatedly colonized toxic, hydrogen sulphide-rich springs. We quantified variation in body size and routine metabolism across replicated sulphidic and non-sulphidic populations in nature, modelled total organismal energy demands, and conducted a common-garden experiment to test whether population differences had a genetic basis. Sulphidic populations generally exhibited smaller body sizes and lower routine metabolic rates compared to non-sulphidic populations, which together caused significant reductions in total organismal energy demands in extremophile populations. Although both mechanisms contributed to variation in organismal energy demands, variance partitioning indicated reductions of body size overall had a greater effect than reductions of routine metabolism. Finally, population differences in routine metabolism documented in natural populations were maintained in common-garden reared individuals, indicating evolved differences. In combination with other studies, these results suggest that reductions in energy demands may represent a common theme in adaptation to physiochemical stressors. Selection for reduced energy demand may particularly affect body size, which has implications for life history evolution in extreme environments. PMID:29077740

Change in convergence and accommodation after two weeks of eye exercises in typical young adults.

PubMed

Horwood, Anna M; Toor, Sonia S; Riddell, Patricia M

2014-04-01

Although eye exercises appear to help heterophoria, convergence insufficiency, and intermittent strabismus, results can be confounded by placebo, practice, and encouragement effects. This study assessed objective changes in vergence and accommodation responses in naive young adults after a 2-week period of eye exercises under controlled conditions to determine the extent to which treatment effects occur over other factors. Asymptomatic young adults were randomly assigned to one of two no-treatment (control) groups or to one of six eye exercise groups: accommodation, vergence, both, convergence in excess of accommodation, accommodation in excess of convergence, and placebo. Subjects were tested and retested under identical conditions, except for the second control group, who were additionally encouraged. Objective accommodation and vergence were assessed to a range of targets moving in depth containing combinations of blur, disparity, and proximity/looming cues. A total of 156 subjects were included. Response gain improved more for less naturalistic targets where more improvement was possible. Convergence exercises improved vergence for near across all targets (P = 0.035). Mean accommodation changed similarly but nonsignificantly. No other treatment group differed significantly from the nonencouraged control group, whereas encouraging effort produced significantly increased vergence (P = 0.004) and accommodation (P = 0.005) gains in the second control group. True treatment effects were small, significantly better only after vergence exercises to a nonaccommodative target, and rarely related to the response they were designed to improve. Exercising accommodation without convergence made no difference to accommodation to cues containing detail. Additional effort improved objective responses the most. Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

Convergence properties of halo merger trees; halo and substructure merger rates across cosmic history

NASA Astrophysics Data System (ADS)

Poole, Gregory B.; Mutch, Simon J.; Croton, Darren J.; Wyithe, Stuart

2017-12-01

We introduce GBPTREES: an algorithm for constructing merger trees from cosmological simulations, designed to identify and correct for pathological cases introduced by errors or ambiguities in the halo finding process. GBPTREES is built upon a halo matching method utilizing pseudo-radial moments constructed from radially sorted particle ID lists (no other information is required) and a scheme for classifying merger tree pathologies from networks of matches made to-and-from haloes across snapshots ranging forward-and-backward in time. Focusing on SUBFIND catalogues for this work, a sweep of parameters influencing our merger tree construction yields the optimal snapshot cadence and scanning range required for converged results. Pathologies proliferate when snapshots are spaced by ≲0.128 dynamical times; conveniently similar to that needed for convergence of semi-analytical modelling, as established by Benson et al. Total merger counts are converged at the level of ∼5 per cent for friends-of-friends (FoF) haloes of size np ≳ 75 across a factor of 512 in mass resolution, but substructure rates converge more slowly with mass resolution, reaching convergence of ∼10 per cent for np ≳ 100 and particle mass mp ≲ 109 M⊙. We present analytic fits to FoF and substructure merger rates across nearly all observed galactic history (z ≤ 8.5). While we find good agreement with the results presented by Fakhouri et al. for FoF haloes, a slightly flatter dependence on merger ratio and increased major merger rates are found, reducing previously reported discrepancies with extended Press-Schechter estimates. When appropriately defined, substructure merger rates show a similar mass ratio dependence as FoF rates, but with stronger mass and redshift dependencies for their normalization.

Convergent validity of six methods to assess physical activity in daily life.

PubMed

Macfarlane, Duncan J; Lee, Cherry C Y; Ho, Edmond Y K; Chan, K L; Chan, Dionise

2006-11-01

The purpose was to examine the agreement (convergent validity) between six common measures of habitual physical activity to estimate durations of light, moderate, vigorous, and total activity in a range of free-living individuals. Over 7 consecutive days, 49 ethnic Chinese (30 men, 19 women), aged 15-55 yr, wore a Polar heart rate monitor, a uniaxial MTI, and triaxial Tritrac accelerometer, plus a Yamax pedometer for > or = 600 min/day. They also completed a daily physical activity log and on day 8 a Chinese version of the 7-day International Physical Activity Questionnaire. At each level of activity, there was good agreement between the two questionnaire-derived instruments and the two accelerometry-derived instruments, but wide variation across different instruments, with two- to fourfold differences in mean durations often seen. The heart rate monitor overestimated light activity and underestimated moderate activity compared with all other measures. Spearman correlation coefficients were low to moderate (0.2-0.5) across most measures of activity, with the pedometer showing correlations with total activity that were often superior to the other movement sensors. We conclude that, with the use of commonly accepted cut points for defining light, moderate, vigorous, and total activity, little convergent validity across the instruments was evident, suggesting these measures are sampling different levels of habitual physical activity and care is needed when comparing their results. To provide a more stable comparison of activity among different people, across studies, or against accepted physical activity promotion guidelines, further work is needed to fine tune the different cut points across a range of common activity monitors to provide more consistent results during free-living conditions.

Total syntheses of hyperforin and papuaforins A-C, and formal synthesis of nemorosone through a gold(I)-catalyzed carbocyclization.

PubMed

Bellavance, Gabriel; Barriault, Louis

2014-06-23

The remarkable biological activities of polyprenylated polycyclic acylphloroglucinols (PPAPs) combined with their highly decorated bicyclo[3.3.1]nonane-2,4,9-trione frameworks have inspired synthetic organic chemists over the last decade. The concise total syntheses of four natural products PPAPs; hyperforin and papuaforins A-C, and the formal synthesis of nemorosone are reported. Key to the realization of this strategy is the short and scalable synthesis of densely substituted PPAP scaffolds through a gold(I)-catalyzed 6-endo-dig carbocyclization of cyclic enol ethers for late-stage functionalization. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents.

PubMed

Nicolaou, K C; Pulukuri, Kiran Kumar; Rigol, Stephan; Buchman, Marek; Shah, Akshay A; Cen, Nicholas; McCurry, Megan D; Beabout, Kathryn; Shamoo, Yousif

2017-11-08

An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.

Cyclic azole-homologated peptides from Marine sponges.

PubMed

Molinski, Tadeusz F

2017-12-19

This review discusses the chemistry of cyclic azole-homologated peptides (AHPs) from the marine sponges, Theonella swinhoei, other Theonella species, Calyx spp. and Plakina jamaicensis. The origin, distribution of AHPs and molecular structure elucidations of AHPs are described followed by their biosynthesis, bioactivity, and synthetic efforts towards their total synthesis. Reports of partial and total synthesis of AHPs extend beyond peptide coupling reactions and include creative construction of the non-proteinogenic amino acid components, mainly the homologated heteroaromatic and α-keto-β-amino acids. A useful conclusion is drawn regarding AHPs: despite their rarity, exotic structures and the potent protease inhibitory properties of some members, their synthesis is under-developed and beckons solutions for outstanding problems towards their efficient assembly.

Targeting tumor-initiating cells: Eliminating anabolic cancer stem cells with inhibitors of protein synthesis or by mimicking caloric restriction

PubMed Central

Lamb, Rebecca; Harrison, Hannah; Smith, Duncan L.; Townsend, Paul A.; Jackson, Thomas; Ozsvari, Bela; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Howell, Anthony; Lisanti, Michael P.; Sotgia, Federica

2015-01-01

We have used an unbiased proteomic profiling strategy to identify new potential therapeutic targets in tumor-initiating cells (TICs), a.k.a., cancer stem cells (CSCs). Towards this end, the proteomes of mammospheres from two breast cancer cell lines were directly compared to attached monolayer cells. This allowed us to identify proteins that were highly over-expressed in CSCs and/or progenitor cells. We focused on ribosomal proteins and protein folding chaperones, since they were markedly over-expressed in mammospheres. Overall, we identified >80 molecules specifically associated with protein synthesis that were commonly upregulated in mammospheres. Most of these proteins were also transcriptionally upregulated in human breast cancer cells in vivo, providing evidence for their potential clinical relevance. As such, increased mRNA translation could provide a novel mechanism for enhancing the proliferative clonal expansion of TICs. The proteomic findings were functionally validated using known inhibitors of protein synthesis, via three independent approaches. For example, puromycin (which mimics the structure of tRNAs and competitively inhibits protein synthesis) preferentially targeted CSCs in both mammospheres and monolayer cultures, and was ~10-fold more potent for eradicating TICs, than “bulk” cancer cells. In addition, rapamycin, which inhibits mTOR and hence protein synthesis, was very effective at reducing mammosphere formation, at nanomolar concentrations. Finally, mammosphere formation was also markedly inhibited by methionine restriction, which mimics the positive effects of caloric restriction in cultured cells. Remarkably, mammosphere formation was >18-fold more sensitive to methionine restriction and replacement, as directly compared to monolayer cell proliferation. Methionine is absolutely required for protein synthesis, since every protein sequence starts with a methionine residue. Thus, the proliferation and survival of CSCs is very sensitive to the inhibition of protein synthesis, using multiple independent approaches. Our findings have important clinical implications, since they may also explain the positive therapeutic effects of PI3-kinase inhibitors and AKT inhibitors, as they ultimately converge on mTOR signaling and would block protein synthesis. We conclude that inhibition of mRNA translation by pharmacological or protein/methionine restriction may be effective strategies for eliminating TICs. Our data also indicate a novel mechanism by which caloric/protein restriction may reduce tumor growth, by targeting protein synthesis in anabolic tumor-initiating cancer cells. PMID:25671304

Psychometric properties of the Portuguese version of the Depressive Cognition Scale in Brazilian adults with diabetes mellitus.

PubMed

Sousa, Valmi D; Zanetti, Maria L; Zauszniewski, Jaclene A; Mendes, Isabel A C; Daguano, Michelle O

2008-01-01

Identifying depressive cognitions in Brazilians with diabetes can be important step to prevent the development of clinical depression, which is negatively associated with diabetes self-management. This study focused on the psychometric testing of the Portuguese version of the Depressive Cognition Scale, the Escala Cognitiva de Depressão (ECD), among 82 Brazilian adults with diabetes mellitus. The questionnaire was assessed for internal consistency, homogeneity, and construct validity using factor analysis and convergent validity assessment with the Portuguese version of the Beck Depression Inventory, the Inventário de Depressão Beck (IDB). Cronbach's alpha for the ECD was .88. The homogeneity of the instrument was supported by item-to-total correlations between .30 and .70. Factor extraction generated only one factor with eigenvalues greater than 1, which is consistent with the English version. The ECD's total score had a weak but significant correlation with the IDB's total score (r = .24, p < .05), indicating convergent validity. Evidence for the reliability and construct validity of the ECD was provided by this study. This scale has the potential to become a useful screening tool for depressive cognitions among Brazilians with diabetes.

Accelerating an Ordered-Subset Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction with a Power Factor and Total Variation Minimization.

PubMed

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2016-01-01

In recent years, there has been increased interest in low-dose X-ray cone beam computed tomography (CBCT) in many fields, including dentistry, guided radiotherapy and small animal imaging. Despite reducing the radiation dose, low-dose CBCT has not gained widespread acceptance in routine clinical practice. In addition to performing more evaluation studies, developing a fast and high-quality reconstruction algorithm is required. In this work, we propose an iterative reconstruction method that accelerates ordered-subsets (OS) reconstruction using a power factor. Furthermore, we combine it with the total-variation (TV) minimization method. Both simulation and phantom studies were conducted to evaluate the performance of the proposed method. Results show that the proposed method can accelerate conventional OS methods, greatly increase the convergence speed in early iterations. Moreover, applying the TV minimization to the power acceleration scheme can further improve the image quality while preserving the fast convergence rate.

Hypersensitivity to sound in tinnitus patients: an analysis of a construct based on questionnaire and audiological data.

PubMed

Bläsing, Lena; Goebel, Gerhard; Flötzinger, Uta; Berthold, Anke; Kröner-Herwig, Birgit

2010-07-01

The purpose of this study was to analyse the Questionnaire on Hypersensitivity to Sound (GUF; Nelting & Finlayson, 2004 ) and to improve its validity based on the analysis of intercorrelations (single item level) with other methods of assessing hyperacusis (uncomfortable loudness level, individual loudness function, self-rated severity of hyperacusis). Subjects consisted of 91 inpatients with tinnitus and hyperacusis. The GUF showed a good reliability (alpha = .92). The factorial structure of the questionnaire reported by Nelting et al (2002) was not completely supported by the evidence in this study. The total score and the single items showed small to moderate correlations with the other modes of measuring hyperacusis. Evidence for convergent and discriminant validity were found, but overall the results corroborate the conceptual heterogeneity of the construct hyperacusis and its dependency on the assessment method. Four items of the GUF with particularly low correlations were excluded from the questionnaire. The revised GUF total score showed slightly but not statistically significant higher convergent and discriminant validity.

Accelerating an Ordered-Subset Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction with a Power Factor and Total Variation Minimization

PubMed Central

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2016-01-01

In recent years, there has been increased interest in low-dose X-ray cone beam computed tomography (CBCT) in many fields, including dentistry, guided radiotherapy and small animal imaging. Despite reducing the radiation dose, low-dose CBCT has not gained widespread acceptance in routine clinical practice. In addition to performing more evaluation studies, developing a fast and high-quality reconstruction algorithm is required. In this work, we propose an iterative reconstruction method that accelerates ordered-subsets (OS) reconstruction using a power factor. Furthermore, we combine it with the total-variation (TV) minimization method. Both simulation and phantom studies were conducted to evaluate the performance of the proposed method. Results show that the proposed method can accelerate conventional OS methods, greatly increase the convergence speed in early iterations. Moreover, applying the TV minimization to the power acceleration scheme can further improve the image quality while preserving the fast convergence rate. PMID:27073853

Electron impact excitation of molecular hydrogen

DOE PAGES

Zammit, Mark Christian; Savage, Jeremy S.; Fursa, Dmitry V.; ...

2017-02-06

Here, we report the electron impact integrated and differential cross sections for excitation to the b 3Σmore » $$+\\atop{u}$$, a 3Σ$$+\\atop{g}$$, c 3Π u, B 1Σ$$+\\atop{u}$$, E, F 1Σ$$+\\atop{g}$$, C 1Π u, e 3Σ$$+\\atop{u}$$, h 3Σ $$+\\atop{g}$$, d 3Π u, B'' 1Σ$$+\\atop{u}$$ , D 1Π u, B'' 1Σ$$+\\atop{u}$$, and D' 1Π u states of molecular hydrogen in the energy range from 10 to 300 eV. Total scattering and total ionization cross sections are also presented. The calculations have been performed by using the convergent close-coupling method within the fixed-nuclei approximation. Detailed convergence studies have been performed with respect to the size of the close-coupling expansion and a set of recommended cross sections has been produced. Significant differences with previous calculations are found. Agreement with experiment is mixed, ranging from excellent to poor depending on the transition and incident energies.« less

Investigation and appreciation of optimal output feedback. Volume 1: A convergent algorithm for the stochastic infinite-time discrete optimal output feedback problem

NASA Technical Reports Server (NTRS)

Halyo, N.; Broussard, J. R.

1984-01-01

The stochastic, infinite time, discrete output feedback problem for time invariant linear systems is examined. Two sets of sufficient conditions for the existence of a stable, globally optimal solution are presented. An expression for the total change in the cost function due to a change in the feedback gain is obtained. This expression is used to show that a sequence of gains can be obtained by an algorithm, so that the corresponding cost sequence is monotonically decreasing and the corresponding sequence of the cost gradient converges to zero. The algorithm is guaranteed to obtain a critical point of the cost function. The computational steps necessary to implement the algorithm on a computer are presented. The results are applied to a digital outer loop flight control problem. The numerical results for this 13th order problem indicate a rate of convergence considerably faster than two other algorithms used for comparison.

CONVERGENT TRANSCRIPTOMICS AND PROTEOMICS OF ENVIRONMENTAL ENRICHMENT AND COCAINE IDENTIFIES NOVEL THERAPEUTIC STRATEGIES FOR ADDICTION

PubMed Central

ZHANG, YAFANG; CROFTON, ELIZABETH J.; FAN, XIUZHEN; LI, DINGGE; KONG, FANPING; SINHA, MALA; LUXON, BRUCE A.; SPRATT, HEIDI M.; LICHTI, CHERYL F.; GREEN, THOMAS A.

2016-01-01

Transcriptomic and proteomic approaches have separately proven effective at identifying novel mechanisms affecting addiction-related behavior; however, it is difficult to prioritize the many promising leads from each approach. A convergent secondary analysis of proteomic and transcriptomic results can glean additional information to help prioritize promising leads. The current study is a secondary analysis of the convergence of recently published separate transcriptomic and proteomic analyses of nucleus accumbens (NAc) tissue from rats subjected to environmental enrichment vs. isolation and cocaine self-administration vs. saline. Multiple bioinformatics approaches (e.g. Gene Ontology (GO) analysis, Ingenuity Pathway Analysis (IPA), and Gene Set Enrichment Analysis (GSEA)) were used to interrogate these rich data sets. Although there was little correspondence between mRNA vs. protein at the individual target level, good correspondence was found at the level of gene/protein sets, particularly for the environmental enrichment manipulation. These data identify gene sets where there is a positive relationship between changes in mRNA and protein (e.g. glycolysis, ATP synthesis, translation elongation factor activity, etc.) and gene sets where there is an inverse relationship (e.g. ribosomes, Rho GTPase signaling, protein ubiquitination, etc.). Overall environmental enrichment produced better correspondence than cocaine self-administration. The individual targets contributing to mRNA and protein effects were largely not overlapping. As a whole, these results confirm that robust transcriptomic and proteomic data sets can provide similar results at the gene/protein set level even when there is little correspondence at the individual target level and little overlap in the targets contributing to the effects. PMID:27717806

A novel body frame based approach to aerospacecraft attitude tracking.

PubMed

Ma, Carlos; Chen, Michael Z Q; Lam, James; Cheung, Kie Chung

2017-09-01

In the common practice of designing an attitude tracker for an aerospacecraft, one transforms the Newton-Euler rotation equations to obtain the dynamic equations of some chosen inertial frame based attitude metrics, such as Euler angles and unit quaternions. A Lyapunov approach is then used to design a controller which ensures asymptotic convergence of the attitude to the desired orientation. Although this design methodology is pretty standard, it usually involves singularity-prone coordinate transformations which complicates the analysis process and controller design. A new, singularity free error feedback method is proposed in the paper to provide simple and intuitive stability analysis and controller synthesis. This new body frame based method utilizes the concept of Euleraxis and angles to generate the smallest error angles from a body frame perspective, without coordinate transformations. Global tracking convergence is illustrated with the use of a feedback linearizing PD tracker, a sliding mode controller, and a model reference adaptive controller. Experimental results are also obtained on a quadrotor platform with unknown system parameters and disturbances, using a boundary layer approximated sliding mode controller, a PIDD controller, and a unit sliding mode controller. Significant tracking quality is attained. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

PubMed Central

Focken, Thilo

2014-01-01

Summary A review of the synthesis of natural products and bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be summarized, as well as an overview of the synthesis of the employed phosphonamide reagents. PMID:25246946

Enantioselective Synthesis of (-)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation.

PubMed

Antropow, Alyssa H; Garcia, Nicholas R; White, Kolby L; Movassaghi, Mohammad

2018-06-04

The first enantioselective total synthesis of (-)-vallesine via a strategy that features a late-stage regioselective C17-oxidation followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by the divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring-oxygenated derivative, (+)-deacetylaspidospermine, the precursor to (-)-vallesine, from a common intermediate.

Pushing the threshold: How NMDAR antagonists induce homeostasis through protein synthesis to remedy depression.

PubMed

Raab-Graham, Kimberly F; Workman, Emily R; Namjoshi, Sanjeev; Niere, Farr

2016-09-15

Healthy neurons have an optimal operating range, coded globally by the frequency of action potentials or locally by calcium. The maintenance of this range is governed by homeostatic plasticity. Here, we discuss how new approaches to treat depression alter synaptic activity. These approaches induce the neuron to recruit homeostatic mechanisms to relieve depression. Homeostasis generally implies that the direction of activity necessary to restore the neuron's critical operating range is opposite in direction to its current activity pattern. Unconventional antidepressant therapies-deep brain stimulation and NMDAR antagonists-alter the neuron's "depressed" state by pushing the neuron's current activity in the same direction but to the extreme edge. These therapies rally the intrinsic drive of neurons in the opposite direction, thereby allowing the cell to return to baseline activity, form new synapses, and restore proper communication. In this review, we discuss seminal studies on protein synthesis dependent homeostatic plasticity and their contribution to our understanding of molecular mechanisms underlying the effectiveness of NMDAR antagonists as rapid antidepressants. Rapid antidepressant efficacy is likely to require a cascade of mRNA translational regulation. Emerging evidence suggests that changes in synaptic strength or intrinsic excitability converge on the same protein synthesis pathways, relieving depressive symptoms. Thus, we address the question: Are there multiple homeostatic mechanisms that induce the neuron and neuronal circuits to self-correct to regulate mood in vivo? Targeting alternative ways to induce homeostatic protein synthesis may provide, faster, safer, and longer lasting antidepressants. This article is part of a Special Issue entitled SI:RNA Metabolism in Disease. Published by Elsevier B.V.

Substitutions in the Glycogenin-1 Gene Are Associated with the Evolution of Endothermy in Sharks and Tunas.

PubMed

Ciezarek, Adam G; Dunning, Luke T; Jones, Catherine S; Noble, Leslie R; Humble, Emily; Stefanni, Sergio S; Savolainen, Vincent

2016-10-05

Despite 400-450 million years of independent evolution, a strong phenotypic convergence has occurred between two groups of fish: tunas and lamnid sharks. This convergence is characterized by centralization of red muscle, a distinctive swimming style (stiffened body powered through tail movements) and elevated body temperature (endothermy). Furthermore, both groups demonstrate elevated white muscle metabolic capacities. All these traits are unusual in fish and more likely evolved to support their fast-swimming, pelagic, predatory behavior. Here, we tested the hypothesis that their convergent evolution was driven by selection on a set of metabolic genes. We sequenced white muscle transcriptomes of six tuna, one mackerel, and three shark species, and supplemented this data set with previously published RNA-seq data. Using 26 species in total (including 7,032 tuna genes plus 1,719 shark genes), we constructed phylogenetic trees and carried out maximum-likelihood analyses of gene selection. We inferred several genes relating to metabolism to be under selection. We also found that the same one gene, glycogenin-1, evolved under positive selection independently in tunas and lamnid sharks, providing evidence of convergent selective pressures at gene level possibly underlying shared physiology. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The remarkable convergence of skull shape in crocodilians and toothed whales

PubMed Central

Evans, Alistair R.; Fitzgerald, Erich M. G.; Adams, Justin W.; Clausen, Philip D.; McHenry, Colin R.

2017-01-01

The striking resemblance of long-snouted aquatic mammals and reptiles has long been considered an example of morphological convergence, yet the true cause of this similarity remains untested. We addressed this deficit through three-dimensional morphometric analysis of the full diversity of crocodilian and toothed whale (Odontoceti) skull shapes. Our focus on biomechanically important aspects of shape allowed us to overcome difficulties involved in comparing mammals and reptiles, which have fundamental differences in the number and position of skull bones. We examined whether diet, habitat and prey size correlated with skull shape using phylogenetically informed statistical procedures. Crocodilians and toothed whales have a similar range of skull shapes, varying from extremely short and broad to extremely elongate. This spectrum of shapes represented more of the total variation in our dataset than between phylogenetic groups. The most elongate species (river dolphins and gharials) are extremely convergent in skull shape, clustering outside of the range of the other taxa. Our results suggest the remarkable convergence between long-snouted river dolphins and gharials is driven by diet rather than physical factors intrinsic to riverine environments. Despite diverging approximately 288 million years ago, crocodilians and odontocetes have evolved a remarkably similar morphological solution to feeding on similar prey. PMID:28275142

The remarkable convergence of skull shape in crocodilians and toothed whales.

PubMed

McCurry, Matthew R; Evans, Alistair R; Fitzgerald, Erich M G; Adams, Justin W; Clausen, Philip D; McHenry, Colin R

2017-03-15

The striking resemblance of long-snouted aquatic mammals and reptiles has long been considered an example of morphological convergence, yet the true cause of this similarity remains untested. We addressed this deficit through three-dimensional morphometric analysis of the full diversity of crocodilian and toothed whale (Odontoceti) skull shapes. Our focus on biomechanically important aspects of shape allowed us to overcome difficulties involved in comparing mammals and reptiles, which have fundamental differences in the number and position of skull bones. We examined whether diet, habitat and prey size correlated with skull shape using phylogenetically informed statistical procedures. Crocodilians and toothed whales have a similar range of skull shapes, varying from extremely short and broad to extremely elongate. This spectrum of shapes represented more of the total variation in our dataset than between phylogenetic groups. The most elongate species (river dolphins and gharials) are extremely convergent in skull shape, clustering outside of the range of the other taxa. Our results suggest the remarkable convergence between long-snouted river dolphins and gharials is driven by diet rather than physical factors intrinsic to riverine environments. Despite diverging approximately 288 million years ago, crocodilians and odontocetes have evolved a remarkably similar morphological solution to feeding on similar prey. © 2017 The Author(s).

Plasma L-5-oxoproline kinetics and whole blood glutathione synthesis rates in severely burned adult humans.

PubMed

Yu, Yong-Ming; Ryan, Colleen M; Fei, Zhe-Wei; Lu, Xiao-Ming; Castillo, Leticia; Schultz, John T; Tompkins, Ronald G; Young, Vernon R

2002-02-01

Compromised glutathione homeostasis is associated with increased morbidity in various disease states. We evaluated the kinetics of L-5-oxoproline, an intermediate in the gamma-glutamyl cycle of glutathione production, in fourteen severely burned adults by use of a primed, constant intravenous infusion of L-5-[1-(13)C]oxoproline. In nine of these patients, whole blood glutathione synthesis and plasma kinetics of glycine and leucine were also measured with [(15)N]glycine and L-[(2)H(3)]leucine tracers. Patients were studied under a "basal" condition that provided a low dose of glucose and total parenteral nutrition. For comparison with control subjects, whole blood glutathione synthesis was estimated in six healthy adults. Burn patients in a basal condition showed significantly higher rates of plasma oxoproline clearance and urinary D- and L-oxoproline excretion compared with fasting healthy control subjects. Whole blood glutathione concentration and absolute synthesis rate in the basal state were lower than for control subjects. Total parenteral feeding without cysteine but with generous methionine did not affect oxoproline kinetics or whole blood glutathione synthesis. The estimated rate of glycine de novo synthesis was also lower in burn patients, suggesting a possible change in glycine availability for glutathione synthesis. The roles of precursor amino acid availability, as well as alterations in metabolic capacity, in modulating whole blood glutathione production in burns now require investigation.

Smoothing and the second law

NASA Technical Reports Server (NTRS)

Merriam, Marshal L.

1987-01-01

The technique of obtaining second-order oscillation-free total -variation-diminishing (TVD), scalar difference schemes by adding a limited diffusive flux ('smoothing') to a second-order centered scheme is explored. It is shown that such schemes do not always converge to the correct physical answer. The approach presented here is to construct schemes that numerically satisfy the second law of thermodynamics on a cell-by-cell basis. Such schemes can only converge to the correct physical solution and in some cases can be shown to be TVD. An explicit scheme with this property and second-order spatial accuracy was found to have extremely restrictive time-step limitation. Switching to an implicit scheme removed the time-step limitation.

Improved techniques for outgoing wave variational principle calculations of converged state-to-state transition probabilities for chemical reactions

NASA Technical Reports Server (NTRS)

Mielke, Steven L.; Truhlar, Donald G.; Schwenke, David W.

1991-01-01

Improved techniques and well-optimized basis sets are presented for application of the outgoing wave variational principle to calculate converged quantum mechanical reaction probabilities. They are illustrated with calculations for the reactions D + H2 yields HD + H with total angular momentum J = 3 and F + H2 yields HF + H with J = 0 and 3. The optimization involves the choice of distortion potential, the grid for calculating half-integrated Green's functions, the placement, width, and number of primitive distributed Gaussians, and the computationally most efficient partition between dynamically adapted and primitive basis functions. Benchmark calculations with 224-1064 channels are presented.

On the convergence of difference approximations to scalar conservation laws

NASA Technical Reports Server (NTRS)

Osher, Stanley; Tadmor, Eitan

1988-01-01

A unified treatment is given for time-explicit, two-level, second-order-resolution (SOR), total-variation-diminishing (TVD) approximations to scalar conservation laws. The schemes are assumed only to have conservation form and incremental form. A modified flux and a viscosity coefficient are introduced to obtain results in terms of the latter. The existence of a cell entropy inequality is discussed, and such an equality for all entropies is shown to imply that the scheme is an E scheme on monotone (actually more general) data, hence at most only first-order accurate in general. Convergence for TVD-SOR schemes approximating convex or concave conservation laws is shown by enforcing a single discrete entropy inequality.

Differential regulation of thyrotropin subunit apoprotein and carbohydrate biosynthesis by thyroid hormone

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

Taylor, T.; Weintraub, B.D.

1985-04-01

The regulation of TSH apoprotein and carbohydrate biosynthesis by thyroid hormone was studied by incubating pituitaries from normal and hypothyroid (3 weeks post-thyroidectomy) rats in medium containing (/sup 14/C)alanine and (/sup 3/H) glucosamine. After 6 h, samples were sequentially treated with anti-TSH beta to precipitate TSH and free TSH beta, anti-LH beta to clear the sample of LH and free LH beta, then anti-LH alpha to precipitate free alpha-subunit. Total proteins were acid precipitated. All precipitates were subjected to electrophoresis on sodium dodecyl sulfate-polyacrylamide gels, which were then sliced and assayed by scintillation spectrometry. In hypothyroid pituitaries plus medium, (/supmore » 14/C)alanine incorporation in combined and free beta-subunits was 26 times normal and considerably greater than the 3.4-fold increase seen in total protein; combined and free alpha-subunits showed no specific increase in apoprotein synthesis. (/sup 3/H)Glucosamine incorporation in combined alpha- and beta-subunits in hypothyroid samples was 13 and 21 times normal, respectively, and was greater than the 1.9-fold increase in total protein; free alpha-subunit showed no specific increase in carbohydrate synthesis. The glucosamine to alanine ratio, reflecting relative glycosylation of newly synthesized molecules, was increased in hypothyroidism for combined alpha-subunits, but not for combined beta-subunits, free alpha-subunits, or total proteins. In summary, short term hypothyroidism selectively stimulated TSH beta apoprotein synthesis and carbohydrate synthesis of combined alpha- and beta-subunits. Hypothyroidism also increased the relative glycosylation of combined alpha-subunit. Thus, thyroid hormone deficiency appears to alter the rate-limiting step in TSH assembly (i.e. beta-subunit synthesis) as well as the carbohydrate structure of TSH, which may play important roles in its biological function.« less

A role for polyamines in glucose-stimulated insulin-gene expression.

PubMed Central

Welsh, N

1990-01-01

The aim of the present study was to evaluate the possible role for polyamines in the glucose regulation of the metabolism of insulin mRNA of pancreatic islet cells. For this purpose islets were prepared from adult mice and cultured for 2 days in culture medium RPMI 1640 containing 3.3 mM- or 16.7 mM-glucose with or without the addition of the inhibitors of polyamine biosynthesis difluoromethylornithine (DFMO) and ethylglyoxal bis(guanylhydrazone) (EGBG). Culture at the high glucose concentration increased the islet contents of both insulin mRNA and polyamines. The synthesis of total RNA, total islet polyamines and polyamines associated with islet nuclei was also increased. When the combination of DFMO and EGBG was added in the presence of 16.7 mM-glucose, low contents of insulin mRNA, spermine and spermidine were observed. Total islet polyamine synthesis was also depressed by DFMO + EGBG, unlike islet biosynthesis of polyamines associated with nuclei, which was not equally decreased by the polyamine-synthesis inhibitors. Total RNA synthesis and turnover was not affected by DFMO + EGBG. Finally, actinomycin D attenuated the glucose-induced enhancement of insulin mRNA, and cycloheximide counteracted the insulin-mRNA attenuation induced by inhibition of polyamine synthesis. It is concluded that the glucose-induced increase in insulin mRNA is paralleled by increased contents and rates of polyamine biosynthesis and that an attenuation of the increase in polyamines prevents the increase in insulin mRNA. In addition, the results are compatible with the view that polyamines exert their effects on insulin mRNA mainly by increasing the stability of this messenger. PMID:2241922

Collective synthesis of natural products by means of organocascade catalysis

PubMed Central

Jones, Spencer B.; Simmons, Bryon; Mastracchio, Anthony; MacMillan, David W. C.

2012-01-01

Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine. PMID:21753848

Total Synthesis and Biological Evaluation of 22-Hydroxyacuminatine

PubMed Central

Xiao, Xiangshu; Antony, Smitha; Pommier, Yves; Cushman, Mark

2008-01-01

A total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from Camptotheca acuminata, is reported. The key step in the synthesis involves the reaction of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12H-5,11a-diazadibenzo[b,h]fluoren-11-one intermediate. Despite its structural resemblance to camptothecin and luotonin A, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase I-deficient cell line P388/CPT45 has confirmed that the observed cytotoxicity is not due to topoisomerase I inhibition. This result is consistent with the hypothesis that π-π stacking is more important than hydrogen bonding interactions in determining topoisomerase I inhibitor binding in the ternary cleavage complex. PMID:16480276

Synthesis of Polycyclic Natural Products

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

Nguyen, Tuan Hoang

With the continuous advancements in molecular biology and modern medicine, organic synthesis has become vital to the support and extension of those discoveries. The isolations of new natural products allow for the understanding of their biological activities and therapeutic value. Organic synthesis is employed to aid in the determination of the relationship between structure and function of these natural products. The development of synthetic methodologies in the course of total syntheses is imperative for the expansion of this highly interdisciplinary field of science. In addition to the practical applications of total syntheses, the structural complexity of natural products represents amore » worthwhile challenge in itself. The pursuit of concise and efficient syntheses of complex molecules is both gratifying and enjoyable.« less

Factors Influencing Biogenic Amines Accumulation in Dairy Products

PubMed Central

Linares, Daniel M.; del Río, Beatriz; Ladero, Victor; Martínez, Noelia; Fernández, María; Martín, María Cruz; Álvarez, Miguel A.

2012-01-01

Fermented foods are among the food products more often complained of having caused episodes of biogenic amines (BA) poisoning. Concerning milk-based fermented foods, cheese is the main product likely to contain potentially harmful levels of BA, specially tyramine, histamine, and putrescine. Prompted by the increasing awareness of the risks related to dietary uptake of high biogenic amine loads, in this review we report all those elaboration and processing technological aspects affecting BA biosynthesis and accumulation in dairy foods. Improved knowledge of the factors involved in the synthesis and accumulation of BA should lead to a reduction in their incidence in milk products. Synthesis of BA is possible only when three conditions converge: (i) availability of the substrate amino acids; (ii) presence of microorganisms with the appropriate catabolic pathway activated; and (iii) environmental conditions favorable to the decarboxylation activity. These conditions depend on several factors such as milk treatment (pasteurization), use of starter cultures, NaCl concentration, time, and temperature of ripening and preservation, pH, temperature, or post-ripening technological processes, which will be discussed in this chapter. PMID:22783233

A Combined Photochemical and Multicomponent Reaction Approach to Precision Oligomers.

PubMed

Konrad, Waldemar; Bloesser, Fabian R; Wetzel, Katharina S; Boukis, Andreas C; Meier, Michael A R; Barner-Kowollik, Christopher

2018-03-07

We introduce the convergent synthesis of linear monodisperse sequence-defined oligomers through a unique approach, combining the Passerini three-component reaction (P-3CR) and a Diels-Alder (DA) reaction based on photocaged dienes. A set of oligomers is prepared resting on a Passerini linker unit carrying an isocyano group for chain extension by P-3CR and a maleimide moiety for photoenol conjugation enabling a modular approach for chain growth. Monodisperse oligomers are accessible in a stepwise fashion by switching between both reaction types. Employing sebacic acid as a core unit allows the synthesis of a library of symmetric sequence-defined oligomers. The oligomers consist of alternating P-3CR and photoblocks with molecular weights up to 3532.16 g mol -1 , demonstrating the successful switching from P-3CR to photoenol conjugation. In-depth characterization was carried out including size-exclusion chromatography (SEC), high-resolution electrospray ionization mass spectrometry (ESI-MS) and NMR spectroscopy, evidencing the monodisperse nature of the precision oligomers. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and biological evaluation of glycogen synthase kinase 3 (GSK-3) inhibitors: an fast and atom efficient access to 1-aryl-3-benzylureas.

PubMed

Monte, Fabio Lo; Kramer, Thomas; Boländer, Alexander; Plotkin, Batya; Eldar-Finkelman, Hagit; Fuertes, Ana; Dominguez, Juan; Schmidt, Boris

2011-09-15

The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-3 inhibitor AR-A014418 (AstraZeneca). This moiety suits both (a) a convergent approach utilizing readily accessible building blocks and (b) a divergent approach based on a microwave heating assisted Suzuki coupling. We established a chromatography-free purification method to generate products with sufficient purity for the biological assays. The structure-activity relationship of the library provided the rationale for the synthesis of the benzothiazolylurea 66 (IC(50)=140 nM) and the pyridylurea 62 (IC(50)=98 nM), which displayed two to threefold enhanced activity versus the reference compound 18 (AR-A014418: IC(50)=330 nM) in our assays. Copyright © 2011. Published by Elsevier Ltd.

Toward a Molecular Lego Approach for the Diversity-Oriented Synthesis of Cyclodextrin Analogues Designed as Scaffolds for Multivalent Systems.

PubMed

Lepage, Mathieu L; Schneider, Jérémy P; Bodlenner, Anne; Compain, Philippe

2015-11-06

A modular strategy has been developed to access a diversity of cyclic and acyclic oligosaccharide analogues designed as prefunctionalized scaffolds for the synthesis of multivalent ligands. This convergent approach is based on bifunctional sugar building blocks with two temporarily masked functionalities that can be orthogonally activated to perform Cu(I)-catalyzed azide-alkyne cycloaddition reactions (CuAAC). The reducing end is activated as a glycosyl azide and masked as a 1,6-anhydro sugar, while the nonreducing end is activated as a free alkyne and masked as a triethylsilyl-alkyne. Following a cyclooligomerization approach, the first examples of close analogues of cyclodextrins composed of d-glucose residues and triazole units bound together through α-(1,4) linkages were obtained. The cycloglucopyranoside analogue containing four sugar units was used as a template to prepare multivalent systems displaying a protected d-mannose derivative or an iminosugar by way of CuAAC. On the other hand, the modular approach led to acyclic alkyne-functionalized scaffolds of a controlled size that were used to synthesize multivalent iminosugars.

Digital robust control law synthesis using constrained optimization

NASA Technical Reports Server (NTRS)

Mukhopadhyay, Vivekananda

1989-01-01

Development of digital robust control laws for active control of high performance flexible aircraft and large space structures is a research area of significant practical importance. The flexible system is typically modeled by a large order state space system of equations in order to accurately represent the dynamics. The active control law must satisy multiple conflicting design requirements and maintain certain stability margins, yet should be simple enough to be implementable on an onboard digital computer. Described here is an application of a generic digital control law synthesis procedure for such a system, using optimal control theory and constrained optimization technique. A linear quadratic Gaussian type cost function is minimized by updating the free parameters of the digital control law, while trying to satisfy a set of constraints on the design loads, responses and stability margins. Analytical expressions for the gradients of the cost function and the constraints with respect to the control law design variables are used to facilitate rapid numerical convergence. These gradients can be used for sensitivity study and may be integrated into a simultaneous structure and control optimization scheme.

A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs.

PubMed

Eniade, Adewale; Purushotham, Madhusudhan; Ben, Robert N; Wang, J B; Horwath, Kathleen

2003-01-01

Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.

Flow cytometric measurement of total DNA and incorporated halodeoxyuridine

DOEpatents

Dolbeare, Frank A.; Gray, Joe W.

1986-01-01

A method for the simultaneous flow cytometric measurement of the total DNA content and the level of DNA synthesis in normal and malignant cells is disclosed. The sensitivity of the method allows a study of cell cycle traverse rates for large scale cell populations as well as single cell measurements. A DNA stain such as propidium iodide is used as the probe for the measurement of total DNA content and a monoclonal antibody reactive with a DNA precursor such as bromodeoxyuridine (BrdU) is used as a probe for the measurement of BrdU uptake by the cells as a measure of DNA synthesis.

Stereoselective Total Synthesis of Radiolabeled Artemisinin (Qinghaosu).

DTIC Science & Technology

Our previous total synthesis of (+)- artemisinin has been optimized from 18 to 11 steps. The final two steps in the sequence are: 1) alkylation of a...product (+)- artemisinin . The first step was repeated utilizing carbon-14 methyl iodide and the sequence completed as before to afford the desired...carbon-14labeled (+)- artemisinin . The label resides in the methyl group pendant from the lactone ring (ring D), the position of attachment being C-9, the carbon atom being C-16. Keywords: Antimalarials. (aw)

Total synthesis and structure-activity investigation of the marine natural product neopeltolide.

PubMed

Custar, Daniel W; Zabawa, Thomas P; Hines, John; Crews, Craig M; Scheidt, Karl A

2009-09-02

The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.

Total Synthesis of Hyperforin.

PubMed

Ting, Chi P; Maimone, Thomas J

2015-08-26

A 10-step total synthesis of the polycyclic polyprenylated acylphloroglucinol (PPAP) natural product hyperforin from 2-methylcyclopent-2-en-1-one is reported. This route was enabled by a diketene annulation reaction and an oxidative ring expansion strategy designed to complement the presumed biosynthesis of this complex meroterpene. The described work enables the preparation of a highly substituted bicyclo[3.3.1]nonane-1,3,5-trione motif in only six steps and thus serves as a platform for the construction of easily synthesized, highly diverse PPAPs modifiable at every position.

Total synthesis of panicein A2

PubMed Central

Yeung, Lili; Pilkington, Lisa I; Cadelis, Melissa M; Copp, Brent R

2015-01-01

Summary The first total synthesis of the unusual aromatic sesquiterpene panicein A2 is reported and the structure of the natural product has been confirmed. When tested by the NCI against a range of human cancer cell lines, it was found that panicein A2 exhibits very little antiproliferative activity at 10 μM – an observation that is at odds with the earlier report that stated panicein A2 exhibits in vitro cytotoxicity against a number of tumour cell lines. PMID:26664619

Biosynthesis and Total Synthesis of Pyrronazol B: a Secondary Metabolite from Nannocystis pusilla.

PubMed

Witte, Swjatoslaw N R; Hug, Joachim J; Géraldy, Magalie N E; Müller, Rolf; Kalesse, Markus

2017-11-13

The first stereoselective total synthesis of the natural product pyrronazol B, which contains a chlorinated pyrrole-oxazole-pyrone framework, has been achieved. Genome sequencing of the myxobacterial producer strain Nannocystis pusilla Ari7 led to the identification of the putative biosynthetic gene cluster. The proposed biosynthetic pathway was supported by feeding experiments with stable isotopes of three biosynthetic building blocks, namely l-proline, l-serine, and l-methionine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

The energetic cost of protein synthesis in isolated hepatocytes of rainbow trout (Oncorhynchus mykiss).

PubMed

Pannevis, M C; Houlihan, D F

1992-01-01

To establish the energetic cost of protein synthesis, isolated trout hepatocytes were used to measure protein synthesis and respiration simultaneously at a variety of temperatures. The presence of bovine serum albumin was essential for the viability of isolated hepatocytes during isolation, but, in order to measure protein synthesis rates, oxygen consumption rates and RNA-to-protein ratios, BSA had to be washed from the cells. Isolated hepatocytes were found to be capable of protein synthesis and oxygen consumption at constant rates over a wide range of oxygen tension. Cycloheximide was used to inhibit protein synthesis. Isolated hepatocytes used on average 79.7 +/- 9.5% of their total oxygen consumption on cycloheximide-sensitive protein synthesis and 2.8 +/- 2.8% on maintaining ouabain-sensitive Na+/K(+)-ATPase activity. The energetic cost of protein synthesis in terms of moles of adenosine triphosphate per gram of protein synthesis decreased with increasing rates of protein synthesis at higher temperatures. It is suggested that the energetic cost consists of a fixed (independent of synthesis rate) and a variable component (dependent on synthesis rate).

Complete solution of electronic excitation and ionization in electron-hydrogen molecule scattering

DOE PAGES

Zammit, Mark C.; Savage, Jeremy S.; Fursa, Dmitry V.; ...

2016-06-08

The convergent close-coupling method has been used to solve the electron-hydrogen molecule scattering problem in the fixed-nuclei approximation. Excellent agreement with experiment is found for the grand total, elastic, electronic-excitation, and total ionization cross sections from the very low to the very high energies. This shows that for the electronic degrees of freedom the method provides a complete treatment of electron scattering on molecules as it does for atoms.

Toward a consensus definition of pathological video-gaming: a systematic review of psychometric assessment tools.

PubMed

King, Daniel L; Haagsma, Maria C; Delfabbro, Paul H; Gradisar, Michael; Griffiths, Mark D

2013-04-01

Pathological video-gaming, or its proposed DSM-V classification of "Internet Use Disorder", is of increasing interest to scholars and practitioners in allied health disciplines. This systematic review was designed to evaluate the standards in pathological video-gaming instrumentation, according to Cicchetti (1994) and Groth-Marnat's (2009) criteria and guidelines for sound psychometric assessment. A total of 63 quantitative studies, including eighteen instruments and representing 58,415 participants, were evaluated. Results indicated that reviewed instrumentation may be broadly characterized as inconsistent. Strengths of available measures include: (i) short length and ease of scoring, (ii) excellent internal consistency and convergent validity, and (iii) potentially adequate data for development of standardized norms for adolescent populations. However, key limitations included: (a) inconsistent coverage of core addiction indicators, (b) varying cut-off scores to indicate clinical status, (c) a lack of a temporal dimension, (d) untested or inconsistent dimensionality, and (e) inadequate data on predictive validity and inter-rater reliability. An emerging consensus suggests that pathological video-gaming is commonly defined by (1) withdrawal, (2) loss of control, and (3) conflict. It is concluded that a unified approach to assessment of pathological video-gaming is needed. A synthesis of extant research efforts by meta-analysis may be difficult in the context of several divergent approaches to assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Total saponins from Rosa laevigata Michx fruit attenuates hepatic steatosis induced by high-fat diet in rats.

PubMed

Dong, Deshi; Qi, Yan; Xu, Lina; Yin, Lianhong; Xu, Youwei; Han, Xu; Zhao, Yanyan; Peng, Jinyong

2014-12-01

The protective effects of total saponins from Rosa laevigata Michx fruit (RLTS) in high-fat diet (HFD)-induced rats were investigated. The results showed that oral administration of RLTS attenuated hepatic steatosis, significantly reduced the levels of body weight, alanine transaminase, aspartate transaminase, total cholesterol, total triglyceride, free fatty acids, low density lipoprotein, blood glucose, insulin and malondialdehyde, and increased high density lipoprotein and glutathione levels compared with the model group. Further investigations showed that RLTS affected fatty acid synthesis, fatty acid β-oxidation, fatty acid ω-oxidation, total cholesterol and triglyceride metabolism and synthesis. Moreover, the extract obviously suppressed HFD-induced oxidative stress and inflammation. These results suggest that RLTS should be developed to be one functional food or health product against non-alcoholic fatty liver disease (NAFLD) in the future.

Inhibition of Rat 5α-Reductase Activity and Testosterone-Induced Sebum Synthesis in Hamster Sebocytes by an Extract of Quercus acutissima Cortex

PubMed Central

Koseki, Junichi; Matsumoto, Takashi; Matsubara, Yosuke; Tsuchiya, Kazuaki; Mizuhara, Yasuharu; Sekiguchi, Kyoji; Nishimura, Hiroaki; Watanabe, Junko; Kaneko, Atsushi; Hattori, Tomohisa; Maemura, Kazuya; Kase, Yoshio

2015-01-01

Objective. Bokusoku (BK) is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (−)-epicatechin gallate, and (−)-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne. PMID:25709710

Deactivating Influence of 3-O-Glycosyl Substituent on Anomeric Reactivity of Thiomannoside Observed in Oligomannoside Synthesis.

PubMed

Zhou, Jun; Lv, Siying; Zhang, Dan; Xia, Fei; Hu, Wenhao

2017-03-03

It has been long recognized that, in chemical glycosylation, the anomeric reactivity of glycosyl donor can be influenced greatly by protecting groups. As opposed to the effects of protecting groups, we report herein a finding on how O-glycosyl substituent can affect the reactivity of oligosaccharyl donor, which in turn should have impact on convergent assembly of oligosaccharide. During our synthetic efforts toward Pichia holstii oligomannoside, a type of α-1,3-linked dimannosyl thioglycosides was found to exhibit unexpected low reactivity toward the activation of NIS/TMSOTf. This observation prompted us to perform a series of comparative reactivity studies, which attributed the donor deactivation to the presence of 3-O-glycosyl substituent, by comparison with O-acetyl group and O-glycosidic linkages at C-4/C-6 positions. To rationalize the unusual phenomenon, we hypothesize that O-glycosyl moiety at C-3 could destabilize the oxocarbenium ion intermediate by additionally increasing the O2-C2-C3-O3 torsional strain, which was further supported by DFT calculation of the hypothetical 4 H 3 -like oxocarbeniums. The observed deactivating influence provides a basis for estimation of donor reactivity and logical selection of synthetic strategy in oligosaccharide synthesis. Following this finding, we opted to use an iterative strategy for the synthesis of targeted pentamannoside 1 by using monomeric thiomannosides that ensured sufficient reactivity.

Microbeads display of proteins using emulsion PCR and cell-free protein synthesis.

PubMed

Gan, Rui; Yamanaka, Yumiko; Kojima, Takaaki; Nakano, Hideo

2008-01-01

We developed a method for coupling protein to its coding DNA on magnetic microbeads using emulsion PCR and cell-free protein synthesis in emulsion. A PCR mixture containing streptavidin-coated microbeads was compartmentalized by water-in-oil (w/o) emulsion with estimated 0.5 template molecules per droplet. The template molecules were amplified and immobilized on beads via bead-linked reverse primers and biotinylated forward primers. After amplification, the templates were sequentially labeled with streptavidin and biotinylated anti-glutathione S-transferase (GST) antibody. The pool of beads was then subjected to cell-free protein synthesis compartmentalized in another w/o emulsion, in which templates were coupled to their coding proteins. We mixed two types of DNA templates of Histidine6 tag (His6)-fused and FLAG tag-fused GST in a ratio of 1:1,000 (His6: FLAG) for use as a model DNA library. After incubation with fluorescein isothiocyanate (FITC)-labeled anti-His6 (C-term) antibody, the beads with the His6 gene were enriched 917-fold in a single-round screening by using flow cytometry. A library with a theoretical diversity of 10(6) was constructed by randomizing the middle four residues of the His6 tag. After a two-round screening, the randomized sequences were substantially converged to peptide-encoding sequences recognized by the anti-His6 antibody.

Performance comparison of attitude determination, attitude estimation, and nonlinear observers algorithms

NASA Astrophysics Data System (ADS)

MOHAMMED, M. A. SI; BOUSSADIA, H.; BELLAR, A.; ADNANE, A.

2017-01-01

This paper presents a brief synthesis and useful performance analysis of different attitude filtering algorithms (attitude determination algorithms, attitude estimation algorithms, and nonlinear observers) applied to Low Earth Orbit Satellite in terms of accuracy, convergence time, amount of memory, and computation time. This latter is calculated in two ways, using a personal computer and also using On-board computer 750 (OBC 750) that is being used in many SSTL Earth observation missions. The use of this comparative study could be an aided design tool to the designer to choose from an attitude determination or attitude estimation or attitude observer algorithms. The simulation results clearly indicate that the nonlinear Observer is the more logical choice.

Robust penalty method for structural synthesis

NASA Technical Reports Server (NTRS)

Kamat, M. P.

1983-01-01

The Sequential Unconstrained Minimization Technique (SUMT) offers an easy way of solving nonlinearly constrained problems. However, this algorithm frequently suffers from the need to minimize an ill-conditioned penalty function. An ill-conditioned minimization problem can be solved very effectively by posing the problem as one of integrating a system of stiff differential equations utilizing concepts from singular perturbation theory. This paper evaluates the robustness and the reliability of such a singular perturbation based SUMT algorithm on two different problems of structural optimization of widely separated scales. The report concludes that whereas conventional SUMT can be bogged down by frequent ill-conditioning, especially in large scale problems, the singular perturbation SUMT has no such difficulty in converging to very accurate solutions.

FeF(3) catalyzed cascade C-C and C-N bond formation: synthesis of differentially substituted triheterocyclic benzothiazole functionalities under solvent-free condition.

PubMed

Atar, Amol B; Jeong, Yeon Tae

2014-05-01

A series of diverse polyfunctionalized triheterocyclic benzothiazoles were easily prepared in excellent yields via the Biginelli reaction of 2-aminobenzothiazole with substituted benzaldehydes and α-methylene ketones using FeF(3) as an expeditious catalyst under solvent-free conditions. The protocol provides a practical and straightforward approach toward highly functionalized triheterocyclic benzothiazole derivatives in excellent yields. The reaction was conveniently promoted by FeF(3) and the catalyst could be recovered easily after the reaction and reused without any loss of its catalytic activity. The advantageous features of this methodology are high atom economy, operational simplicity, shorter reaction time, convergence, and facile automation.

“Synthesis-on” and “synthesis-off” modes of carbon arc operation during synthesis of carbon nanotubes

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

Yatom, Shurik; Selinsky, Rachel S.; Koel, Bruce E.

Arc discharge synthesis of single-walled carbon nanotubes (SWCNTs) remains largely uncontrollable, due to incomplete understanding of the synthetic process itself. Here, we show that synthesis of SWCNTs by a carbon arc may not constitute a single continuous process, but may instead consist of two distinct modes. One of these, a “synthesis-on” mode, produces the majority of the nanomaterials. During the synthesis-on mode, proportionally more carbon nanotubes are collected than in another mode, a “synthesis-off” mode. Both synthesis-on and synthesis-off modes for a typical arc configuration, employing a hollow anode filled with a mixture of powdered metal catalyst and graphite, weremore » characterized by using in situ electrical, imaging, and spectroscopic diagnostics, along with ex situ imaging and spectroscopy. The synthesis-on mode duration is rare compared to the total arc run-time, helping to explain the poor selectivity found in the final collected products, a known inadequacy of arc synthesis. Finally, the rarity of the synthesis on mode occurence may be due to the synthesis off mode being more favorable energetically.« less

“Synthesis-on” and “synthesis-off” modes of carbon arc operation during synthesis of carbon nanotubes

DOE PAGES

Yatom, Shurik; Selinsky, Rachel S.; Koel, Bruce E.; ...

2017-09-09

Arc discharge synthesis of single-walled carbon nanotubes (SWCNTs) remains largely uncontrollable, due to incomplete understanding of the synthetic process itself. Here, we show that synthesis of SWCNTs by a carbon arc may not constitute a single continuous process, but may instead consist of two distinct modes. One of these, a “synthesis-on” mode, produces the majority of the nanomaterials. During the synthesis-on mode, proportionally more carbon nanotubes are collected than in another mode, a “synthesis-off” mode. Both synthesis-on and synthesis-off modes for a typical arc configuration, employing a hollow anode filled with a mixture of powdered metal catalyst and graphite, weremore » characterized by using in situ electrical, imaging, and spectroscopic diagnostics, along with ex situ imaging and spectroscopy. The synthesis-on mode duration is rare compared to the total arc run-time, helping to explain the poor selectivity found in the final collected products, a known inadequacy of arc synthesis. Finally, the rarity of the synthesis on mode occurence may be due to the synthesis off mode being more favorable energetically.« less

Education and Italian Regional Development

ERIC Educational Resources Information Center

Di Liberto, Adriana

2008-01-01

In this paper, we study the connection between growth and human capital in a convergence regression for the panel of Italian regions. We include measures of average primary, secondary and tertiary education. We find that increased education seems to contribute to growth only in the South. Decomposing total schooling into its three constituent…

The War on Terror, Intelligence Convergence, and Privacy

DTIC Science & Technology

2012-05-31

surveillance directed at domestic threats to U.S. national security.”17 Then, in reaction to Watergate and other “ scandals that involved overreaching into U.S...killing, and the propriety of the Total Information Awareness data-mining program. The list continues with what some label as scandals such as NSA

Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers.

PubMed

Chai, Weiwen; Liebman, Michael; Kynast-Gales, Susan; Massey, Linda

2004-12-01

Increased rates of either oxalate absorption or endogenous oxalate synthesis can contribute to hyperoxaluria, a primary risk factor for the formation of calcium oxalate-containing kidney stones. This study involves a comparative assessment of oxalate absorption and endogenous oxalate synthesis in subpopulations of stone formers (SFs) and non-stone formers (NSFs) and an assessment of the effect of ascorbate supplementation on oxalate absorption and endogenous oxalate synthesis. Twenty-nine individuals with a history of calcium oxalate kidney stones (19 men, 10 women) and 19 age-matched NSFs (8 men, 11 women) participated in two 6-day controlled feeding experimental periods: ascorbate-supplement (2 g/d) and no-supplement treatments. An oxalate load consisting of 118 mg of unlabeled oxalate and 18 mg of 13C2 -oxalic acid was administered the morning of day 6 of each experimental period. Mean 13C2 -oxalic acid absorption averaged across the ascorbate and no-supplement treatments was significantly greater in SFs (9.9%) than NSFs (8.0%). SFs also had significantly greater 24-hour post-oxalate load urinary total oxalate and endogenous oxalate levels with both treatments. Twenty-four-hour urinary total oxalate level correlated strongly with both 13C2 -oxalic acid absorption (SFs, r = 0.76; P < 0.01; NSFs, r = 0.62; P < 0.01) and endogenous oxalate synthesis (SFs, r = 0.95; P < 0.01; NSFs, r = 0.92; P < 0.01). SFs are characterized by greater rates of both oxalate absorption and endogenous oxalate synthesis, and both these factors contribute to the hyperoxaluric state. The finding that ascorbate supplementation increased urinary total and endogenous oxalate levels suggested that this practice is a risk factor for individuals predisposed to kidney stones.

Synthesis of t-Butyl (2R)-Hydroxyisovalerate, A Precursor of Aureobasidin B

NASA Astrophysics Data System (ADS)

Maharani, R.; Puspitasari, D.; Taufiqqurahman; Huspa, D. H. P.; Hidayat, A. T.; Sumiarsa, D.; Hidayat, I. W.

2017-02-01

Aureobasidins are a family of cyclodepsipeptides have antifungal properties. They were isolated from the black yeast Aureobasidium pullulans R106 and over 30 derivatives have been successfully characterized. There are few publications reporting the total synthesis of aureobasidins. The limited reports of the synthesis of the aureobasidin derivatives are due to the difficult access to the preparations of precursors. The aim of this research is to synthesise a precursor of aureobasidin B, t-butyl (2R)-hydroxyisovalerate (t-Bu-Hiv), that is prepared for the total synthesis of aureobasidin B. The synthesis of AbB is planned to be undertaken by using a solid phase method, so the ester formation between t-Bu-Hiv and the Fmoc-β-hydroxymethylvaline will be carried out in solution phase to form depsidipeptide. The t-butyl group was used as protecting agent that is due to the straightforward elimination of the protecting group from the Fmoc-depsidipeptide. The t-Bu-Hiv acid was prepared from D-valine through diazotisation to form (2R)-acetyloxyisovaleric acid in 62.7% yield. Product of the first step was then protected by t-butyl group by using Boc-anhydride in t-butanol to give t-butil (2R)-acetyloxyisovalerate in 44% yield. In the last step, the acetyloxy group was eliminated by using potassium carbonate in methanol/water to give the desired product, t-Bu-Hiv in 33.5% yield. The t-Bu-Hiv is ready to be combined with Fmoc-β-hydroxymethylvaline to result in depsidipeptide that will be attached to the resin in the total synthesis of AbB. Each stage of this synthesis was controlled by thin layer chromatography and all products were purified by open column chromatography. All the synthesized products were characterized by various spectroscopic techniques, including infrared spectrophotometer, mass spectroscopy (ESI-MS), 1H-NMR and 13C-NMR.

Total variation approach for adaptive nonuniformity correction in focal-plane arrays.

PubMed

Vera, Esteban; Meza, Pablo; Torres, Sergio

2011-01-15

In this Letter we propose an adaptive scene-based nonuniformity correction method for fixed-pattern noise removal in imaging arrays. It is based on the minimization of the total variation of the estimated irradiance, and the resulting function is optimized by an isotropic total variation approach making use of an alternating minimization strategy. The proposed method provides enhanced results when applied to a diverse set of real IR imagery, accurately estimating the nonunifomity parameters of each detector in the focal-plane array at a fast convergence rate, while also forming fewer ghosting artifacts.

Large scale fabrication of highly monodispersed rattle-type TiO2@void@SiO2 spheres via synthesis-cum-organization process.

PubMed

Wu, Liangzhuan; Yu, Yuan; Zhang, Yuan; Li, Yuzhen; Zhang, Yang; Zhi, Jinfang

2012-03-01

Architected nanostructures with interior space have attracted enormous attention due to both their esthetic beauty and their potential applications. It is a current dream to develop a template-free, one-pot and low-temperature synthetic routes for hetero-architecture in liquid media. In this manuscript, we develop a kind of template-free, low-temperature, and one-pot total synthetic strategy for synthesis of inorganic multi-component hetero-architecture. This synthetic strategy analogous to standard organic reactions used in total synthesis is an important breakthrough in inorganic chemical synthesis. We can achieve 1 kilogram (kg) yield of the TiO(2)@void@SiO(2) core-shell sphere one time by using this synthetic strategy, which may lead to practical applications of the sample. By embodying the new reaction and concept into future investigation, a more mature research field in synthetic architecture of nanomaterials can be anticipated. Copyright © 2011 Elsevier Inc. All rights reserved.

The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

NASA Technical Reports Server (NTRS)

Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

1978-01-01

During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro.

PubMed

Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R; Alsner, Jan

2015-01-01

The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account.

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro

PubMed Central

Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R.; Alsner, Jan

2015-01-01

Background The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Methods Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Results Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. Conclusions We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account. PMID:26274822

Total chemical synthesis of proteins without HPLC purification† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc01883a Click here for additional data file.

PubMed Central

Loibl, S. F.; Harpaz, Z.; Zitterbart, R.

2016-01-01

The total chemical synthesis of proteins is a tedious and time-consuming endeavour. The typical steps involve solid phase synthesis of peptide thioesters and cysteinyl peptides, native chemical ligation (NCL) in solution, desulfurization or removal of ligation auxiliaries in the case of extended NCL as well as many intermediary and final HPLC purification steps. With an aim to facilitate and improve the throughput of protein synthesis we developed the first method for the rapid chemical total on-resin synthesis of proteins that proceeds without a single HPLC-purification step. The method relies on the combination of three orthogonal protein tags that allow sequential immobilization (via the N-terminal and C-terminal ends), extended native chemical ligation and release reactions. The peptide fragments to be ligated are prepared by conventional solid phase synthesis and used as crude materials in the subsequent steps. An N-terminal His6 unit permits selective immobilization of the full length peptide thioester onto Ni-NTA agarose beads. The C-terminal peptide fragment carries a C-terminal peptide hydrazide and an N-terminal 2-mercapto-2-phenyl-ethyl ligation auxiliary, which serves as a reactivity tag for the full length peptide. As a result, only full length peptides, not truncation products, react in the subsequent on-bead extended NCL. After auxiliary removal the ligation product is liberated into solution upon treatment with mild acid, and is concomitantly captured by an aldehyde-modified resin. This step allows the removal of the most frequently observed by-product in NCL chemistry, i.e. the hydrolysed peptide thioester (which does not contain a C-terminal peptide hydrazide). Finally, the target protein is released with diluted hydrazine or acid. We applied the method in the synthesis of 46 to 126 amino acid long MUC1 proteins comprising 2–6 copies of a 20mer tandem repeat sequence. Only three days were required for the parallel synthesis of 9 MUC1 proteins which were obtained in 8–33% overall yield with 90–98% purity despite the omission of HPLC purification. PMID:28451120

Collective synthesis of natural products by means of organocascade catalysis.

PubMed

Jones, Spencer B; Simmons, Bryon; Mastracchio, Anthony; MacMillan, David W C

2011-07-13

Organic chemists are now able to synthesize small quantities of almost any known natural product, given sufficient time, resources and effort. However, translation of the academic successes in total synthesis to the large-scale construction of complex natural products and the development of large collections of biologically relevant molecules present significant challenges to synthetic chemists. Here we show that the application of two nature-inspired techniques, namely organocascade catalysis and collective natural product synthesis, can facilitate the preparation of useful quantities of a range of structurally diverse natural products from a common molecular scaffold. The power of this concept has been demonstrated through the expedient, asymmetric total syntheses of six well-known alkaloid natural products: strychnine, aspidospermidine, vincadifformine, akuammicine, kopsanone and kopsinine. ©2011 Macmillan Publishers Limited. All rights reserved

Total synthesis and structural revision of the marine macrolide neopeltolide.

PubMed

Custar, Daniel W; Zabawa, Thomas P; Scheidt, Karl A

2008-01-23

The total synthesis and structural revision of the marine natural product neopeltolide is reported. The key bond-forming step involves a Lewis acid-catalyzed intramolecular cyclization to install the tetrahydropyran ring and the macrocycle simultaneously. This type of cyclization is the first of its kind and assembles the carbon backbone of the natural product efficiently. The synthesis of the reported structure revealed differences in the data between the natural and synthetic material. After significant investigation, the diastereomeric molecule with the C11 and C13 configurations inverted was synthesized using the initial route. This compound matches the data reported for neopeltolide (1H, 13C, HRMS, IR, NOESY, [alpha]), thereby establishing the correct overall structure for this potent macrolide natural product, including the relative and absolute stereochemistry.

Generating a Generation of Proteasome Inhibitors: From Microbial Fermentation to Total Synthesis of Salinosporamide A (Marizomib) and Other Salinosporamides

PubMed Central

Potts, Barbara C.; Lam, Kin S.

2010-01-01

The salinosporamides are potent proteasome inhibitors among which the parent marine-derived natural product salinosporamide A (marizomib; NPI-0052; 1) is currently in clinical trials for the treatment of various cancers. Methods to generate this class of compounds include fermentation and natural products chemistry, precursor-directed biosynthesis, mutasynthesis, semi-synthesis, and total synthesis. The end products range from biochemical tools for probing mechanism of action to clinical trials materials; in turn, the considerable efforts to produce the target molecules have expanded the technologies used to generate them. Here, the full complement of methods is reviewed, reflecting remarkable contributions from scientists of various disciplines over a period of 7 years since the first publication of the structure of 1. PMID:20479958

Synthesis and degradation of phenylalanine ammonia-lyase of Rhodosporidium toruloides.

PubMed

Gilbert, H J; Tully, M

1982-05-01

The regulation of the enzyme phenylalanine ammonia-lyase (PAL), which is of potential use in oral treatment of phenylketonuria, was investigated. Antiserum against PAL was prepared and was shown to be monospecific for the enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native enzyme and two inactive mutant forms of the enzyme were purified to homogeneity by immunoaffinity chromatography, using anti-PAL immunoglobulin G-Sepharose 4B. Both mutant enzymes contained intact prosthetic groups. The formation of PAL catalytic activity after phenylalanine was added to yeast cultures was paralleled by the appearance of enzyme antigen. During induction, uptake of [3H]leucine into the enzyme was higher than uptake into total protein. Our results are consistent with de novo synthesis of an enzyme induced by phenylalanine, rather than activation of a proenzyme. The half-lives of PAL and total protein were similar in both exponential and stationary phase cultures. No metabolite tested affected the rate of enzyme degradation. Glucose repressed enzyme synthesis, whereas ammonia reduced phenylalanine uptake and pool size and so may repress enzyme synthesis through inducer exclusion. The synthesis of enzyme antigen by a mutant unable to metabolize phenylalanine indicated that this amino acid is the physiological inducer of the enzyme.

Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

PubMed

Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

2018-03-01

Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

NUCLEIC ACID AND PROTEIN METABOLISM DURING THE MITOTIC CYCLE IN VICIA FABA

PubMed Central

Woodard, John; Rasch, Ellen; Swift, Hewson

1961-01-01

In order to investigate some of the cytochemical processes involved in interphase growth and culminating in cell division, a combined autoradiographic and microphotometric study of nucleic acids and proteins was undertaken on statistically seriated cells of Vicia faba root meristems. Adenine-8-C14 and uridine-H3 were used as ribonucleic acid (RNA) precursors, thymidine-H3 as a deoxyribonucleic acid (DNA) precursor, and phenylalanine-3-C14 as a protein precursor. Stains used in microphotometry were Feulgen (DNA), azure B (RNA), pH 2.0 fast green (total protein), and pH 8.1 fast green (histone). The autoradiographic data (representing rate of incorporation per organelle) and the microphotometric data (representing changes in amounts of the various components) indicate that the mitotic cycle may be divided into several metabolic phases, three predominantly anabolic (net increase), and a fourth phase predominantly catabolic (net decrease). The anabolic periods are: 1. Telophase to post-telophase during which there are high rates of accumulation of cytoplasmic and nucleolar RNA and nucleolar and chromosomal total protein. 2. Post-telophase to preprophase characterized by histone synthesis and a diphasic synthesis of DNA with the peak of synthesis at mid-interphase and a minor peak just preceding prophase. The minor peak is coincident with a relatively localized DNA synthesis in several chromosomal regions. This period is also characterized by minimal accumulations of cytoplasmic RNA and chromosomal and nucleolar total protein and RNA. 3. Preprophase to prophase in which there are again high rates of accumulation of cytoplasmic RNA, and nucleolar and chromosomal total protein and RNA. The catabolic phase is: 4. The mitotic division during which there are marked losses of cytoplasmic RNA and chromosomal and nucleolar total protein and RNA. PMID:13786522

Total synthesis of a CD-ring: side-chain building block for preparing 17-epi-calcitriol derivatives from the Hajos-Parrish dione.

PubMed

Michalak, Karol; Wicha, Jerzy

2011-08-19

An efficient synthesis of the key building block for 17-epi-calctriol from the Hajos-Parrish dione involving a sequence of diastereoselective transformation of the azulene core and the side-chain construction is presented.

Flow cytometric measurement of total DNA and incorporated halodeoxyuridine

DOEpatents

Dolbeare, F.A.; Gray, J.W.

1983-10-18

A method for the simultaneous flow cylometric measurement of total cellular DNA content and of the uptake of DNA precursors as a measure of DNA synthesis during various phases of the cell cycle in normal and malignant cells in vitro and in vivo is described. The method comprises reacting cells with labelled halodeoxyuridine (HdU), partially denaturing cellular DNA, adding to the reaction medium monoclonal antibodies (mabs) reactive with HdU, reacting the bound mabs with a second labelled antibody, incubating the mixture with a DNA stain, and measuring simultaneously the intensity of the DNA stain as a measure of the total cellular DNA and the HdU incorporated as a measure of DNA synthesis. (ACR)

Flow cytometric measurement of total DNA and incorporated halodeoxyuridine

DOEpatents

Dolbeare, Frank A.; Gray, Joe W.

1988-01-01

A method for the simultaneous flow cytometric measurement of the total DNA content and the level of DNA synthesis in normal and malignant cells is disclosed. The sensitivity of the method allows a study of cell cycle traverse rates for large scale cell populations as well as single cell measurements. A DNA stain such as propidium iodide or Hoechst 33258 is used as the probe for the measurement of total DNA content and a monoclonal antibody reactive with a DNA precursor such as halodeoxy-uridine (HdU), more specifically bromodeoxyuridine (BrdU) is used as a probe for the measurement of HdU or BrdU uptake by the cells as a measure of DNA synthesis.

Impacts of planet migration models on planetary populations. Effects of saturation, cooling and stellar irradiation

NASA Astrophysics Data System (ADS)

Dittkrist, K.-M.; Mordasini, C.; Klahr, H.; Alibert, Y.; Henning, T.

2014-07-01

Context. Several recent studies have found that planet migration in adiabatic disks differs significantly from migration in isothermal disks. Depending on the thermodynamic conditions, that is, the effectiveness of radiative cooling, and on the radial surface density profile, planets migrate inward or outward. Clearly, this will influence the semimajor-axis-to-mass distribution of planets predicted by population-synthesis simulations. Aims: Our goal is to study the global effects of radiative cooling, viscous torque desaturation, gap opening, and stellar irradiation on the tidal migration of a synthetic planet population. Methods: We combined results from several analytical studies and 3D hydrodynamic simulations in a new semi-analytical migration model for the application in our planet population synthesis calculations. Results: We find a good agreement of our model with torques obtained in 3D radiative hydrodynamic simulations. A typical disk has three convergence zones to which migrating planets move from the in- and outside. This strongly affects the migration behavior of low-mass planets. Interestingly, this leads to a slow type II like migration behavior for low-mass planets captured in these zones even without an ad hoc migration rate reduction factor or a yet-to-be-defined halting mechanism. This means that the new prescription of migration that includes nonisothermal effects makes the previously widely used artificial migration rate reduction factor obsolete. Conclusions: Outward migration in parts of a disk helps some planets to survive long enough to become massive. The convergence zones lead to potentially observable accumulations of low-mass planets at certain semimajor axes. Our results indicate that more studies of the mass at which the corotation torque saturates are needed since its value has a main impact on the properties of planet populations. Appendices A and B are available in electronic form at http://www.aanda.org

Smoothing and the second law

NASA Technical Reports Server (NTRS)

Merriam, Marshal L.

1986-01-01

The technique of obtaining second order, oscillation free, total variation diminishing (TVD), scalar difference schemes by adding a limited diffusion flux (smoothing) to a second order centered scheme is explored. It is shown that such schemes do not always converge to the correct physical answer. The approach presented here is to construct schemes that numerically satisfy the second law of thermodynamics on a cell by cell basis. Such schemes can only converge to the correct physical solution and in some cases can be shown to be TVD. An explicit scheme with this property and second order spatial accuracy was found to have an extremely restrictive time step limitation (Delta t less than Delta x squared). Switching to an implicit scheme removed the time step limitation.

Study on transfer optimization of urban rail transit and conventional public transport

NASA Astrophysics Data System (ADS)

Wang, Jie; Sun, Quan Xin; Mao, Bao Hua

2018-04-01

This paper mainly studies the time optimization of feeder connection between rail transit and conventional bus in a shopping center. In order to achieve the goal of connecting rail transportation effectively and optimizing the convergence between the two transportations, the things had to be done are optimizing the departure intervals, shorting the passenger transfer time and improving the service level of public transit. Based on the goal that has the minimum of total waiting time of passengers and the number of start of classes, establish the optimizing model of bus connecting of departure time. This model has some constrains such as transfer time, load factor, and the convergence of public transportation grid spacing. It solves the problems by using genetic algorithms.

Parallel evolution of auditory genes for echolocation in bats and toothed whales.

PubMed

Shen, Yong-Yi; Liang, Lu; Li, Gui-Sheng; Murphy, Robert W; Zhang, Ya-Ping

2012-06-01

The ability of bats and toothed whales to echolocate is a remarkable case of convergent evolution. Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4, both of which are associated with voltage motility during the cochlear amplification of signals. Echolocation involves complex mechanisms. The most important factors include cochlear amplification, nerve transmission, and signal re-coding. Herein, we screen three genes that play different roles in this auditory system. Cadherin 23 (Cdh23) and its ligand, protocadherin 15 (Pcdh15), are essential for bundling motility in the sensory hair. Otoferlin (Otof) responds to nerve signal transmission in the auditory inner hair cell. Signals of parallel evolution occur in all three genes in the three groups of echolocators--two groups of bats (Yangochiroptera and Rhinolophoidea) plus the dolphin. Significant signals of positive selection also occur in Cdh23 in the Rhinolophoidea and dolphin, and Pcdh15 in Yangochiroptera. In addition, adult echolocating bats have higher levels of Otof expression in the auditory cortex than do their embryos and non-echolocation bats. Cdh23 and Pcdh15 encode the upper and lower parts of tip-links, and both genes show signals of convergent evolution and positive selection in echolocators, implying that they may co-evolve to optimize cochlear amplification. Convergent evolution and expression patterns of Otof suggest the potential role of nerve and brain in echolocation. Our synthesis of gene sequence and gene expression analyses reveals that positive selection, parallel evolution, and perhaps co-evolution and gene expression affect multiple hearing genes that play different roles in audition, including voltage and bundle motility in cochlear amplification, nerve transmission, and brain function.

Three-phase Interstellar Medium in Galaxies Resolving Evolution with Star Formation and Supernova Feedback (TIGRESS): Algorithms, Fiducial Model, and Convergence

NASA Astrophysics Data System (ADS)

Kim, Chang-Goo; Ostriker, Eve C.

2017-09-01

We introduce TIGRESS, a novel framework for multi-physics numerical simulations of the star-forming interstellar medium (ISM) implemented in the Athena MHD code. The algorithms of TIGRESS are designed to spatially and temporally resolve key physical features, including: (1) the gravitational collapse and ongoing accretion of gas that leads to star formation in clusters; (2) the explosions of supernovae (SNe), both near their progenitor birth sites and from runaway OB stars, with time delays relative to star formation determined by population synthesis; (3) explicit evolution of SN remnants prior to the onset of cooling, which leads to the creation of the hot ISM; (4) photoelectric heating of the warm and cold phases of the ISM that tracks the time-dependent ambient FUV field from the young cluster population; (5) large-scale galactic differential rotation, which leads to epicyclic motion and shears out overdense structures, limiting large-scale gravitational collapse; (6) accurate evolution of magnetic fields, which can be important for vertical support of the ISM disk as well as angular momentum transport. We present tests of the newly implemented physics modules, and demonstrate application of TIGRESS in a fiducial model representing the solar neighborhood environment. We use a resolution study to demonstrate convergence and evaluate the minimum resolution {{Δ }}x required to correctly recover several ISM properties, including the star formation rate, wind mass-loss rate, disk scale height, turbulent and Alfvénic velocity dispersions, and volume fractions of warm and hot phases. For the solar neighborhood model, all these ISM properties are converged at {{Δ }}x≤slant 8 {pc}.

Achieving a "Grand Convergence" in Global Health: Modeling the Technical Inputs, Costs, and Impacts from 2016 to 2030.

PubMed

Boyle, Colin F; Levin, Carol; Hatefi, Arian; Madriz, Solange; Santos, Nicole

2015-01-01

The Commission on Investing in Health published its report, GlobalHealth2035, in 2013, estimating an investment case for a grand convergence in health outcomes globally. In support of the drafting of the Sustainable Development Goals (SDGs), we estimate what the grand convergence investment case might achieve-and what investment would be required-by 2030. Our projection focuses on a sub-set of low-income (LIC) or lower-middle-income countries (LMIC). We start with a country-based (bottom-up) analysis of the costs and impact of scaling up reproductive, maternal, and child health tools, and select HIV and malaria interventions. We then incorporate global (top-down) analyses of the costs and impacts of scaling up existing tools for tuberculosis, additional HIV interventions, the costs to strengthen health systems, and the costs and benefits from scaling up new health interventions over the time horizon of this forecast. These data are then allocated to individual countries to provide an aggregate projection of potential cost and impact at the country level. Finally, incremental costs of R&D for low-income economies and the costs of addressing NTDs are added to provide a global total cost estimate of the investment scenario. Compared with a constant coverage scenario, there would be more than 60 million deaths averted in LIC and 70 million deaths averted in LMIC between 2016 and 2030. For the years 2015, 2020, 2025, and 2030, the incremental costs of convergence in LIC would be (US billion) $24.3, $21.8, $24.7, and $27, respectively; in LMIC, the incremental costs would be (US billion) $34.75, $38.9, $48.7, and $56.3, respectively. Key health outcomes in low- and low-middle income countries can significantly converge with those of wealthier countries by 2030, and the notion of a "grand convergence" may serve as a unifying theme for health indicators in the SDGs.

[The changing role of the state in health care systems in OECD countries--research questions, research design and first results].

PubMed

Helmert, U; Cacace, M; Grimmeisen, S; Wendt, C; Rothgang, H

2005-02-01

In the framework of the DFG-Research-Unit 597 "Transformation of the State" is Project C3 investigating the change of the role of the state in health care systems in OECD-countries between 1970 and 2000. The primary research hypothesis is, that a tendency of convergence exists regarding the role of the state for the three main dimensions of health care systems, namely service provision, financing and regulation. This is carried out firstly based on a quantitative oriented analysis for 23 OECD-countries, utilising the data set "OECD Health Data 2002", and secondly with qualitative oriented country-studies for England, Germany and the U.S. Findings for the qualitative country-studies give some hints of convergence regarding the "private-public-mix" between the health system types "social insurance" (Germany), "national health system" (England), and "market oriented health system" (USA). First quantitative results concerning the changing role of the state in relation to the health care systems in OECD-countries provide evidence for a convergence process between these states in the financing dimension. For the dependent variable "total health care costs in % of gross domestic product" a trend of convergence is observed for the members states of the European Union (n = 12), while in the remaining Non-EU countries (n = 11) a trend of divergence is identified. For the same parameter we found a convergence for OECD-countries of the type "national health system" (n = 14). For OECD-countries of the type "social insurance" (n = 8) this convergence process is observed only for the time period 1970 - 1980. Some results confirm the hypothesis of the "growth to limits" (Flora). But it appears to us that in future other significant factors like globalisation processes, the increasing potentials of the medical technology and demographic changes may play an important role for the overall health budget and specific needs of the population in the OECD-states.

Total Synthesis and Structure-Activity Investigation of the Marine Natural Product Neopeltolide

PubMed Central

Custar, Daniel W.; Zabawa, Thomas P.; Hines, John; Crews, Craig M.; Scheidt, Karl A.

2009-01-01

The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity. PMID:19663512

What can alcohol researchers learn from research about the relationship between macro-level gender equality and violence against women?

PubMed

Roberts, Sarah C M

2011-01-01

This systematic review focuses on research about macro-level gender equality and violence against women (VAW) and identifies conceptually and theoretically driven hypotheses as well as lessons relevant for alcohol research. Hypotheses include: amelioration--increased equality decreases VAW; backlash--increased equality increases VAW; and convergence--increased equality reduces the gender gap; and hypotheses that distinguish between relative and absolute status, with relative status comparing men's and women's status and absolute status measuring women's status without regard to men. Systematic review of studies published through June 2009 identified through PubMed and Web of Science, as well as citing and cited articles. A total of 30 studies are included. Of 85 findings examining amelioration/backlash, 25% support amelioration, 22% backlash; and 53% are null. Of 13 findings examining convergence, 31% support and 23% are inconsistent with convergence; 46% are null. Neither the existence nor the direction of the equality and VAW relationship can be assumed. This suggests that the relationship between macro-level gender equality and alcohol should also not be assumed, but rather investigated through research.

Pilot study about dose-effect relationship of ocular injury in argon laser photocoagulation

NASA Astrophysics Data System (ADS)

Chen, P.; Zhang, C. P.; Fu, X. B.; Zhang, T. M.; Wang, C. Z.; Qian, H. W.; San, Q.

2011-03-01

The aim of this article was to study the injury effect of either convergent or parallel argon laser beam on rabbit retina, get the dose-effect relationship for the two types of laser beams, and calculate the damage threshold of argon laser for human retinas. An argon laser therapeutic instrument for ophthalmology was used in this study. A total of 80 rabbit eyes were irradiated for 600 lesions, half of which were treated by convergent laser and the other half were done with parallel laser beam. After irradiation, slit lamp microscope and fundus photography were used to observe the lesions, change and the incidence of injury was processed statistically to get the damage threshold of rabbit retina. Based on results from the experiments on animals and the data from clinical cases of laser treatment, the photocoagulation damage thresholds of human retinas for convergent and parallel argon laser were calculated to be 0.464 and 0.285 mJ respectively. These data provided biological reference for safely operation when employing laser photocoagulation in clinical practice and other fields.

Hospital Anxiety and Depression Scale: Factor Structure, Internal Consistency and Convergent Validity in Patients with Dizziness.

PubMed

Piker, Erin G; Kaylie, David M; Garrison, Douglas; Tucci, Debara L

2015-01-01

Psychiatric comorbidities, particularly anxiety-related pathologies, are often observed in dizzy patients. The Hospital Anxiety and Depression Scale (HADS) is a widely used self-report instrument used to screen for anxiety and depression in medical outpatient settings. The purpose of this study was to assess the factor structure, internal consistency and convergent validity of the HADS in an unselected group of patients with dizziness. The HADS and the Dizziness Handicap Inventory (DHI) were administered to 205 dizzy patients. An exploratory factor analysis was conducted and indicated a 3-factor structure, inconsistent with the 2-subscale structure (i.e. anxiety and depression) of the HADS. The total scale was found to be internally consistent, and convergent validity, as assessed using the DHI, was acceptable. Overall findings suggest that the HADS should not be used as a tool for psychiatric differential diagnosis, but rather as a helpful screener for general psychiatric distress in the two domains of psychiatric illness most germane in dizzy patients. © 2015 S. Karger AG, Basel.

Convergence of strain energy release rate components for edge-delaminated composite laminates

NASA Technical Reports Server (NTRS)

Raju, I. S.; Crews, J. H., Jr.; Aminpour, M. A.

1987-01-01

Strain energy release rates for edge delaminated composite laminates were obtained using quasi 3 dimensional finite element analysis. The problem of edge delamination at the -35/90 interfaces of an 8-ply composite laminate subjected to uniform axial strain was studied. The individual components of the strain energy release rates did not show convergence as the delamination tip elements were made smaller. In contrast, the total strain energy release rate converged and remained unchanged as the delamination tip elements were made smaller and agreed with that calculated using a classical laminated plate theory. The studies of the near field solutions for a delamination at an interface between two dissimilar isotropic or orthotropic plates showed that the imaginary part of the singularity is the cause of the nonconvergent behavior of the individual components. To evaluate the accuracy of the results, an 8-ply laminate with the delamination modeled in a thin resin layer, that exists between the -35 and 90 plies, was analyzed. Because the delamination exists in a homogeneous isotropic material, the oscillatory component of the singularity vanishes.

Error detection and data smoothing based on local procedures

NASA Technical Reports Server (NTRS)

Guerra, V. M.

1974-01-01

An algorithm is presented which is able to locate isolated bad points and correct them without contaminating the rest of the good data. This work has been greatly influenced and motivated by what is currently done in the manual loft. It is not within the scope of this work to handle small random errors characteristic of a noisy system, and it is therefore assumed that the bad points are isolated and relatively few when compared with the total number of points. Motivated by the desire to imitate the loftsman a visual experiment was conducted to determine what is considered smooth data. This criterion is used to determine how much the data should be smoothed and to prove that this method produces such data. The method utimately converges to a set of points that lies on the polynomial that interpolates the first and last points; however convergence to such a set is definitely not the purpose of our algorithm. The proof of convergence is necessary to demonstrate that oscillation does not take place and that in a finite number of steps the method produces a set as smooth as desired.

The Parting Parent Concern Inventory: Parents' appraisals correlate with divorced family functioning.

PubMed

Sanford, Keith; Rivers, Alannah Shelby

2017-10-01

When married parents go through a divorce, they may have concerns in 6 areas that are associated with postdivorce family adjustment. These include concerns about malice, power, custody, child rejection, esteem, and finances. The Parting Parent Concern Inventory assesses these concerns. It was developed in a series of preliminary studies, and this report focuses on results from 2 subsequent validation studies including 643 divorced parents with at least 1 child from their former marriage under the age of 18. Participants completed Internet assessments of their concerns and 14 different convergent validity criterion variables regarding aspects of child internalizing behavior, coparenting relationships, settlement outcomes, and personal well-being. Across both studies, the new measure of concerns fit an expected 6-dimensional factor structure. A total of 25 convergent validity correlations were tested, and all were significant. The distinctiveness of each concern scale was supported by the fact that all but 1 convergent association remained significant after controlling for variance explained by other concern scales. These results provide preliminary validation support for the new instrument. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Gravitational convergence, shear deformation and rotation of magnetic forcelines

NASA Astrophysics Data System (ADS)

Giantsos, Vangelis; Tsagas, Christos G.

2017-11-01

We consider the 'kinematics' of space-like congruences and apply them to a family of self-gravitating magnetic forcelines. Our aim is to investigate the convergence and the possible focusing of these lines, as well as their rotation and shear deformation. In so doing, we introduce a covariant 1+2 splitting of the 3-D space, parallel and orthogonal to the direction of the field lines. The convergence, or not, of the latter is monitored by a specific version of the Raychaudhuri equation, obtained after propagating the spatial divergence of the unit magnetic vector along its own direction. The resulting expression shows that, although the convergence of the magnetic forcelines is affected by the gravitational pull of all the other sources, it is unaffected by the field's own gravity, irrespective of how strong the latter is. This rather counterintuitive result is entirely due to the magnetic tension, namely to the negative pressure the field exerts parallel to its lines of force. In particular, the magnetic tension always cancels out the field's energy-density input to the Raychaudhuri equation, leaving the latter free of any direct magnetic-energy contribution. Similarly, the rotation and the shear deformation of the aforementioned forcelines are also unaffected by the magnetic input to the total gravitational energy. In a sense, the magnetic lines do not seem to 'feel' their own gravitational field no matter how strong the latter may be.

Combining Acceleration Techniques for Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction.

PubMed

Huang, Hsuan-Ming; Hsiao, Ing-Tsung

2017-01-01

Over the past decade, image quality in low-dose computed tomography has been greatly improved by various compressive sensing- (CS-) based reconstruction methods. However, these methods have some disadvantages including high computational cost and slow convergence rate. Many different speed-up techniques for CS-based reconstruction algorithms have been developed. The purpose of this paper is to propose a fast reconstruction framework that combines a CS-based reconstruction algorithm with several speed-up techniques. First, total difference minimization (TDM) was implemented using the soft-threshold filtering (STF). Second, we combined TDM-STF with the ordered subsets transmission (OSTR) algorithm for accelerating the convergence. To further speed up the convergence of the proposed method, we applied the power factor and the fast iterative shrinkage thresholding algorithm to OSTR and TDM-STF, respectively. Results obtained from simulation and phantom studies showed that many speed-up techniques could be combined to greatly improve the convergence speed of a CS-based reconstruction algorithm. More importantly, the increased computation time (≤10%) was minor as compared to the acceleration provided by the proposed method. In this paper, we have presented a CS-based reconstruction framework that combines several acceleration techniques. Both simulation and phantom studies provide evidence that the proposed method has the potential to satisfy the requirement of fast image reconstruction in practical CT.

Oblique collision and deformation partitioning in the SW Iberian Variscides

NASA Astrophysics Data System (ADS)

Pérez-Cáceres, Irene; Simancas, José Fernando; Martínez Poyatos, David; Azor, Antonio; González Lodeiro, Francisco

2016-05-01

Different transpressional scenarios have been proposed to relate kinematics and complex deformation patterns. We apply the most suitable of them to the Variscan orogeny in SW Iberia, which is characterized by a number of successive left-lateral transpressional structures developed in the Devonian to Carboniferous period. These structures resulted from the oblique convergence between three continental terranes (Central Iberian Zone, Ossa-Morena Zone and South Portuguese Zone), whose amalgamation gave way to both intense shearing at the suture-like contacts and transpressional deformation of the continental pieces in-between, thus showing strain partitioning in space and time. We have quantified the kinematics of the collisional convergence by using the available data on folding, shearing and faulting patterns, as well as tectonic fabrics and finite strain measurements. Given the uncertainties regarding the data and the boundary conditions modeled, our results must be considered as a semi-quantitative approximation to the issue, though very significant from a regional point of view. The total collisional convergence surpasses 1000 km, most of them corresponding to left-lateral displacement parallel to terrane boundaries. The average vector of convergence is oriented E-W (present-day coordinates), thus reasserting the left-lateral oblique collision in SW Iberia, in contrast with the dextral component that prevailed elsewhere in the Variscan orogen. This particular kinematics of SW Iberia is understood in the context of an Avalonian plate salient currently represented by the South Portuguese Zone.

Reading Habits of College Students in the United States

ERIC Educational Resources Information Center

Huang, SuHua; Capps, Matthew; Blacklock, Jeff; Garza, Mary

2014-01-01

This study employed a convergent mixed-method research design to investigate reading habits of American college students. A total of 1,265 (466 male and 799 female) college students voluntarily participated in the study by completing a self-reported survey. Twelve students participated in semi-structured interviews and classroom observations.…

Factorial Validity and Psychometric Examination of the Exercise Dependence Scale-Revised

ERIC Educational Resources Information Center

Downs, Danielle Symons; Hausenblas, Heather A.; Nigg, Claudio R.

2004-01-01

The research purposes were to examine the factorial and convergent validity, internal consistency, and test-retest reliability of the Exercise Dependence Scale (EDS). Two separate studies, containing a total of 1,263 college students, were undertaken to accomplish these purposes. Participants completed the EDS and measures of exercise behavior and…

Tropospheric wet refractivity tomography using multiplicative algebraic reconstruction technique

NASA Astrophysics Data System (ADS)

Xiaoying, Wang; Ziqiang, Dai; Enhong, Zhang; Fuyang, K. E.; Yunchang, Cao; Lianchun, Song

2014-01-01

Algebraic reconstruction techniques (ART) have been successfully used to reconstruct the total electron content (TEC) of the ionosphere and in recent years be tentatively used in tropospheric wet refractivity and water vapor tomography in the ground-based GNSS technology. The previous research on ART used in tropospheric water vapor tomography focused on the convergence and relaxation parameters for various algebraic reconstruction techniques and rarely discussed the impact of Gaussian constraints and initial field on the iteration results. The existing accuracy evaluation parameters calculated from slant wet delay can only evaluate the resultant precision of the voxels penetrated by slant paths and cannot evaluate that of the voxels not penetrated by any slant path. The paper proposes two new statistical parameters Bias and RMS, calculated from wet refractivity of the total voxels, to improve the deficiencies of existing evaluation parameters and then discusses the effect of the Gaussian constraints and initial field on the convergence and tomography results in multiplicative algebraic reconstruction technique (MART) to reconstruct the 4D tropospheric wet refractivity field using simulation method.

Auxiliary variables for numerically solving nonlinear equations with softly broken symmetries.

PubMed

Olum, Ken D; Masoumi, Ali

2017-06-01

General methods for solving simultaneous nonlinear equations work by generating a sequence of approximate solutions that successively improve a measure of the total error. However, if the total error function has a narrow curved valley, the available techniques tend to find the solution after a very large number of steps, if ever. The solver first converges rapidly to the valley, but once there it converges extremely slowly to the solution. In this paper we show that in the specific physically important case where these valleys are the result of a softly broken symmetry, the solution can often be found much more quickly by adding the generators of the softly broken symmetry as auxiliary variables. This makes the number of variables more than the equations and hence there will be a family of solutions, any one of which would be acceptable. We present a procedure for finding solutions in this case and apply it to several simple examples and an important problem in the physics of false vacuum decay. We also provide a Mathematica package that implements Powell's hybrid method with the generalization to allow more variables than equations.

By-passing the sign-problem in Fermion Path Integral Monte Carlo simulations by use of high-order propagators

NASA Astrophysics Data System (ADS)

Chin, Siu A.

2014-03-01

The sign-problem in PIMC simulations of non-relativistic fermions increases in serverity with the number of fermions and the number of beads (or time-slices) of the simulation. A large of number of beads is usually needed, because the conventional primitive propagator is only second-order and the usual thermodynamic energy-estimator converges very slowly from below with the total imaginary time. The Hamiltonian energy-estimator, while more complicated to evaluate, is a variational upper-bound and converges much faster with the total imaginary time, thereby requiring fewer beads. This work shows that when the Hamiltonian estimator is used in conjunction with fourth-order propagators with optimizable parameters, the ground state energies of 2D parabolic quantum-dots with approximately 10 completely polarized electrons can be obtain with ONLY 3-5 beads, before the onset of severe sign problems. This work was made possible by NPRP GRANT #5-674-1-114 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the author.

An interior-point method for total variation regularized positron emission tomography image reconstruction

NASA Astrophysics Data System (ADS)

Bai, Bing

2012-03-01

There has been a lot of work on total variation (TV) regularized tomographic image reconstruction recently. Many of them use gradient-based optimization algorithms with a differentiable approximation of the TV functional. In this paper we apply TV regularization in Positron Emission Tomography (PET) image reconstruction. We reconstruct the PET image in a Bayesian framework, using Poisson noise model and TV prior functional. The original optimization problem is transformed to an equivalent problem with inequality constraints by adding auxiliary variables. Then we use an interior point method with logarithmic barrier functions to solve the constrained optimization problem. In this method, a series of points approaching the solution from inside the feasible region are found by solving a sequence of subproblems characterized by an increasing positive parameter. We use preconditioned conjugate gradient (PCG) algorithm to solve the subproblems directly. The nonnegativity constraint is enforced by bend line search. The exact expression of the TV functional is used in our calculations. Simulation results show that the algorithm converges fast and the convergence is insensitive to the values of the regularization and reconstruction parameters.

[Reliability and validity of Driving Anger Scale in professional drivers in China].

PubMed

Li, Z; Yang, Y M; Zhang, C; Li, Y; Hu, J; Gao, L W; Zhou, Y X; Zhang, X J

2017-11-10

Objective: To assess the reliability and validity of the Chinese version of Driving Anger Scale (DAS) in professional drivers in China and provide a scientific basis for the application of the scale in drivers in China. Methods: Professional drivers, including taxi drivers, bus drivers, truck drivers and school bus drivers, were selected to complete the questionnaire. Cronbach's α and split-half reliability were calculated to evaluate the reliability of DAS, and content, contract, discriminant and convergent validity were performed to measure the validity of the scale. Results: The overall Cronbach's α of DAS was 0.934 and the split-half reliability was 0.874. The correlation coefficient of each subscale with the total scale was 0.639-0.922. The simplified version of DAS supported a presupposed six-factor structure, explaining 56.371% of the total variance revealed by exploratory factor analysis. The DAS had good convergent and discriminant validity, with the success rate of calibration experiment of 100%. Conclusion: DAS has a good reliability and validity in professional drivers in China, and the use of DAS is worth promoting in divers.

Design and Stereoselective Preparation of a New Class of Chiral Olefin Metathesis Catalysts and Application to Enantioselective Synthesis of Quebrachamine: Catalyst Development Inspired by Natural Product Synthesis

PubMed Central

Sattely, Elizabeth S.; Meek, Simon J.; Malcolmson, Steven J.; Schrock, Richard R.; Hoveyda, Amir H.

2010-01-01

A total synthesis of the Aspidosperma alkaloid quebrachamine in racemic form is first described. A key catalytic ring-closing metathesis of an achiral triene is used to establish the all-carbon quaternary stereogenic center and the tetracyclic structure of the natural product; the catalytic transformation proceeds with reasonable efficiency through the use of existing achiral Ru or Mo catalysts. Ru- or Mo-based chiral olefin metathesis catalysts have proven to be inefficient and entirely nonselective in cases where the desired product is observed. In the present study, the synthesis route thus serves as a platform for the discovery of new olefin metathesis catalysts that allow for efficient completion of an enantioselective synthesis of quebrachamine. Accordingly, on the basis of mechanistic principles, stereogenic-at-Mo complexes bearing only monodentate ligands have been designed. The new catalysts provide significantly higher levels of activity than observed with the previously reported Ru- or Mo-based complexes. Enantiomerically enriched chiral alkylidenes are generated through diastereoselective reactions involving achiral Mo-based bispyrrolides and enantiomerically pure silyl-protected binaphthols. Such chiral catalysts initiate the key enantioselective ring-closing metathesis step in the total synthesis of quebrachamine efficiently (1 mol % loading, 22 °C, 1 h, >98% conversion, 84% yield) and with high selectivity (98:2 er, 96% ee). PMID:19113867

Enantioselective Total Synthesis of Natural Isoflavans: Asymmetric Transfer Hydrogenation/Deoxygenation of Isoflavanones with Dynamic Kinetic Resolution.

PubMed

Keßberg, Anton; Lübken, Tilo; Metz, Peter

2018-05-02

A concise and highly enantioselective synthesis of structurally diverse isoflavans from a single chromone is described. The key transformation is a single-step conversion of racemic isoflavanones into virtually enantiopure isoflavans by domino asymmetric transfer hydrogenation/deoxygenation with dynamic kinetic resolution.

Synthesis of (+)-Antroquinonol: An Antihyperglycemic Agent.

PubMed

Sulake, Rohidas S; Lin, Hsiao-Han; Hsu, Chia-Yu; Weng, Ching-Feng; Chen, Chinpiao

2015-06-19

The total synthesis of antroquinonol has been accomplished through Suzuki-Miyaura cross-coupling and Barton-McCombie reaction, and the α,β-unsaturation was achieved through selenylation and oxidation protocols. In vitro and in vivo studies on the glucose-lowering properties of antroquinonol indicate that it is a potential antidiabetic agent.

Microwave assisted total synthesis of a benzothiophene-based new chemical entity (NCE)

EPA Science Inventory

Pharmaceutical scientists are required to generate diverse arrays of complex targets in short span of time, which can now be achieved by microwave-assisted organic synthesis. New chemical entities (NCE) can be built in a fraction of the time using this technique. However, there a...

The Achilles tendon total rupture score: a study of responsiveness, internal consistency and convergent validity on patients with acute Achilles tendon ruptures

PubMed Central

2012-01-01

Background The Achilles tendon Total Rupture Score was developed by a research group in 2007 in response to the need for a patient reported outcome measure for this patient population. Beyond this original development paper, no further validation studies have been published. Consequently the purpose of this study was to evaluate internal consistency, convergent validity and responsiveness of this newly developed patient reported outcome measure within patients who have sustained an isolated acute Achilles tendon rupture. Methods Sixty-four eligible patients with an acute rupture of their Achilles tendon completed the Achilles tendon Total Rupture Score alongside two further patient reported outcome measures (Disability Rating Index and EQ 5D). These were completed at baseline, six weeks, three months, six months and nine months post injury. The Achilles tendon Total Rupture Score was evaluated for internal consistency, using Cronbach's alpha, convergent validity, through correlation analysis and responsiveness, by analysing floor and ceiling effects and calculating its relative efficiency in comparison to the Disability Rating Index and EQ 5D scores. Results The Achilles tendon Total Rupture Score demonstrated high internal consistency (Cronbachs alpha > 0.8) and correlated significantly (p < 0.001) with the Disability Rating Index at five time points (pre-injury, six weeks, three, six and nine months) with correlation coefficients between -0.5 and -0.9. However, the confidence intervals were wide. Furthermore, the ability of the new score to detect clinically important changes over time (responsiveness) was shown to be greater than the Disability Rating Index and EQ 5D. Conclusions A universally accepted outcome measure is imperative to allow comparisons to be made across practice. This is the first study to evaluate aspects of validity of this newly developed outcome measure, outside of the developing centre. The ATRS demonstrated high internal consistency and responsiveness, with limited convergent validity. This research provides further support for the use of this outcome measure, however further research is required to advocate its universal use in patients with acute Achilles tendon ruptures. Such areas include inter-rater reliability and research to determine the minimally clinically important difference between scores. All authors have read and concur with the content of this manuscript. The material presented has not been and will not be submitted for publication elsewhere, except as an abstract. All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content and (3) final approval of the submitted version. This research has been funded by Arthritis Research UK, no conflicts of interests have been declared by the authors. Kind Regards Rebecca Kearney (corresponding author) Research Physiotherapist PMID:22376047

Efficient data communication protocols for wireless networks

NASA Astrophysics Data System (ADS)

Zeydan, Engin

In this dissertation, efficient decentralized algorithms are investigated for cost minimization problems in wireless networks. For wireless sensor networks, we investigate both the reduction in the energy consumption and throughput maximization problems separately using multi-hop data aggregation for correlated data in wireless sensor networks. The proposed algorithms exploit data redundancy using a game theoretic framework. For energy minimization, routes are chosen to minimize the total energy expended by the network using best response dynamics to local data. The cost function used in routing takes into account distance, interference and in-network data aggregation. The proposed energy-efficient correlation-aware routing algorithm significantly reduces the energy consumption in the network and converges in a finite number of steps iteratively. For throughput maximization, we consider both the interference distribution across the network and correlation between forwarded data when establishing routes. Nodes along each route are chosen to minimize the interference impact in their neighborhood and to maximize the in-network data aggregation. The resulting network topology maximizes the global network throughput and the algorithm is guaranteed to converge with a finite number of steps using best response dynamics. For multiple antenna wireless ad-hoc networks, we present distributed cooperative and regret-matching based learning schemes for joint transmit beanformer and power level selection problem for nodes operating in multi-user interference environment. Total network transmit power is minimized while ensuring a constant received signal-to-interference and noise ratio at each receiver. In cooperative and regret-matching based power minimization algorithms, transmit beanformers are selected from a predefined codebook to minimize the total power. By selecting transmit beamformers judiciously and performing power adaptation, the cooperative algorithm is shown to converge to pure strategy Nash equilibrium with high probability throughout the iterations in the interference impaired network. On the other hand, the regret-matching learning algorithm is noncooperative and requires minimum amount of overhead. The proposed cooperative and regret-matching based distributed algorithms are also compared with centralized solutions through simulation results.

Convergent evolution of Darwin's finches caused by introgressive hybridization and selection.

PubMed

Grant, Peter R; Grant, B Rosemary; Markert, Jeffrey A; Keller, Lukas F; Petren, K

2004-07-01

Between 1973 and 2003 mean morphological features of the cactus finch, Geospiza scandens, and the medium ground finch, G. fortis, populations on the Galápagos island of Daphne Major were subject to fluctuating directional selection. An increase in bluntness or robustness in the beak of G. scandens after 1990 can only partly be explained by selection. We use 16 microsatellite loci to test predictions of the previously proposed hypothesis that introgressive hybridization contributed to the trend, resulting in genes flowing predominantly from G. fortis to G. scandens. To identify F1 hybrids and backcrosses we use pedigrees where known, supplemented by the results of assignment tests based on 14 autosomal loci when parents were not known. We analyze changes in morphology and allelic composition in the two populations over a period of 15-20 years. With samples that included F1 hybrids and backcrosses, the G. scandens population became more similar to the G. fortis population both genetically and morphologically. Gene flow between species was estimated to be three times greater from G. fortis to G. scandens than in the opposite direction, resulting in a 20% reduction in the genetic difference between the species. Nevertheless, removing identified F1 hybrids and backcrosses from the total sample and reanalyzing the traits did not eliminate the convergence. The two species also converged in beak shape by 22.2% and in body size by 45.5%. A combination of introgressive hybridization and selection jointly provide the best explanation of convergence in morphology and genetic constitution under the changed ecological conditions following a major El Niño event in 1983. The study illustrates how species without postmating barriers to gene exchange can alternate between convergence and divergence when environmental conditions oscillate.

Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid.

PubMed

Martínez-Gualda, Belén; Sun, Liang; Rivero-Buceta, Eva; Flores, Aida; Quesada, Ernesto; Balzarini, Jan; Noppen, Sam; Liekens, Sandra; Schols, Dominique; Neyts, Johan; Leyssen, Pieter; Mirabelli, Carmen; Camarasa, María-José; San-Félix, Ana

2017-03-01

We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a "decarboxylated" analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Small-scale early aggregation of green tide macroalgae observed on the Subei Bank, Yellow Sea.

PubMed

Hu, Song; Yang, Hong; Zhang, Jianheng; Chen, Changsheng; He, Peimin

2014-04-15

Massive green algae blooms became an environmental disaster in the Yellow Sea from 2008 to 2013. Recent studies suggested that recurrences of early aggregates of macroalgae were found over the Subei Bank, a unique shallow radial sand ridge system off the Jiangsu coast, China. Yearly field surveys have been carried out over this bank during the past five years (2009-2013), with an aim at identifying and qualifying the physical-biological mechanism for the early aggregation of algae. Data synthesis showed that early aggregation of macroalgae usually occurred from April-May as small-scale patches either over the intertidal mudflat of the Subei Bank or along local isobaths in the northern coastal area north of the bank. Both hydrographic and current measurements were performed by tracking a narrow patchy area of floating macroalgae (nearly 4 km in length and 5-10 m in width) on April 26, 2013, and the results showed that the algae aggregation was mainly caused by tide-induced convergence. This convergence was produced by the local geometrically controlled interaction of tidal currents with mudflats, which is believed to be a key physical mechanism for the early development of algal blooms in addition to marine ecosystem responses and human aquaculture activities. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of synthetic homopolymer poly I:C on the synthesis of nucleic acids, protein and interferon in spleen cells normally and with radiation

NASA Technical Reports Server (NTRS)

Antropova, Y. N.; Konstantinova, I. V.; Fuks, B. B.; Talosh, M. Y.; Veysfeyler, Y. K.

1974-01-01

A comparative study is reported of the effect of the synthetic homopolymer poly I:C and Newcastle Disease virus on the synthesis of RNA, DNA, total protein and interferon in the spleen of nonradiated and radiated mice. In radiated animals, poly I:C and NDV had no stimulating effect on the synthesis of RNA; administration of both inducers to radiated mice did not significantly affect the content of lymphoid cellular elements in the spleen. However, while reduction of RNA synthesis, caused by radiation, also increases slightly under the effect of poly I:C and the virus, the synthesis of interferon in spleen cells and in the entire body is activated.

Convergence Studies of Mass Transport in Disks with Gravitational Instabilities. I. The Constant Cooling Time Case

NASA Astrophysics Data System (ADS)

Michael, Scott; Steiman-Cameron, Thomas Y.; Durisen, Richard H.; Boley, Aaron C.

2012-02-01

We conduct a convergence study of a protostellar disk, subject to a constant global cooling time and susceptible to gravitational instabilities (GIs), at a time when heating and cooling are roughly balanced. Our goal is to determine the gravitational torques produced by GIs, the level to which transport can be represented by a simple α-disk formulation, and to examine fragmentation criteria. Four simulations are conducted, identical except for the number of azimuthal computational grid points used. A Fourier decomposition of non-axisymmetric density structures in cos (mphi), sin (mphi) is performed to evaluate the amplitudes Am of these structures. The Am , gravitational torques, and the effective Shakura & Sunyaev α arising from gravitational stresses are determined for each resolution. We find nonzero Am for all m-values and that Am summed over all m is essentially independent of resolution. Because the number of measurable m-values is limited to half the number of azimuthal grid points, higher-resolution simulations have a larger fraction of their total amplitude in higher-order structures. These structures act more locally than lower-order structures. Therefore, as the resolution increases the total gravitational stress decreases as well, leading higher-resolution simulations to experience weaker average gravitational torques than lower-resolution simulations. The effective α also depends upon the magnitude of the stresses, thus αeff also decreases with increasing resolution. Our converged αeff is consistent with predictions from an analytic local theory for thin disks by Gammie, but only over many dynamic times when averaged over a substantial volume of the disk.

Nanotechnology Applications and Implications of Agrochemicals toward Sustainable Agriculture and Food Systems.

PubMed

Scott, Norman R; Chen, Hongda; Cui, Haixin

2018-06-08

The first international conference on Nanotechnology Applications and Implications of Agrochemicals toward Sustainable Agriculture and Food Systems was held in Beijing, China on November 17-18, 2016 to address and exchange latest knowledge and developments in nanotechnology of agrochemicals toward sustainable agriculture and food systems. World-leading scientists gathered to discuss a wide range of relevant topics. The purposes of this paper are to provide: an introduction to the international conference, summarize in brief the contributions of papers that follow within this special issue of Journal of Agricultural and Food Chemistry, provide a synthesis of conference outcomes, suggest future directions including an important role of converging science and technologies to advance sustainable agriculture, food, and natural resource systems.

Analysis of glycoprotein processing in the endoplasmic reticulum using synthetic oligosaccharides.

PubMed

Ito, Yukishige; Takeda, Yoichi

2012-01-01

Protein quality control (QC) in the endoplasmic reticulum (ER) comprises many steps, including folding and transport of nascent proteins as well as degradation of misfolded proteins. Recent studies have revealed that high-mannose-type glycans play a pivotal role in the QC process. To gain knowledge about the molecular basis of this process with well-defined homogeneous compounds, we achieved a convergent synthesis of high-mannose-type glycans and their functionalized derivatives. We focused on analyses of UDP-Glc: glycoprotein glucosyltransferase (UGGT) and ER Glucosidase II, which play crucial roles in glycoprotein QC; however, their specificities remain unclear. In addition, we established an in vitro assay system mimicking the in vivo condition which is highly crowded because of the presence of various biomacromolecules.

Decentralized state estimation for a large-scale spatially interconnected system.

PubMed

Liu, Huabo; Yu, Haisheng

2018-03-01

A decentralized state estimator is derived for the spatially interconnected systems composed of many subsystems with arbitrary connection relations. An optimization problem on the basis of linear matrix inequality (LMI) is constructed for the computations of improved subsystem parameter matrices. Several computationally effective approaches are derived which efficiently utilize the block-diagonal characteristic of system parameter matrices and the sparseness of subsystem connection matrix. Moreover, this decentralized state estimator is proved to converge to a stable system and obtain a bounded covariance matrix of estimation errors under certain conditions. Numerical simulations show that the obtained decentralized state estimator is attractive in the synthesis of a large-scale networked system. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Synthesis of new bioactive aminophosphonates and study of their antioxidant, anti-inflammatory and antibacterial activities as well the assessment of their toxicological activity

NASA Astrophysics Data System (ADS)

Damiche, Rebiha; Chafaa, Salah

2017-02-01

Two new categories of α-aminophosphonates molecules were synthesized and characterized by UV-Vis, IR, and NMR. Their spectral properties show a perfect convergence. Their biological activities were evaluated. Molecules 1a, 2a, and 1d present a greater antioxidant potential than BHT and vitamin C. The best anti-inflammatory activity is shown by the 2b molecule and that of 1a, 2a, and 2c molecules are closely comparable to that of diclofenac. The antibacterial activity of the synthesized compounds is significantly higher than the antibiotic amoxicillin. The hemolysis rate HR of compounds 1b, 1c, 2b, and 2c was lower than 5%.

A hybrid nonlinear programming method for design optimization

NASA Technical Reports Server (NTRS)

Rajan, S. D.

1986-01-01

Solutions to engineering design problems formulated as nonlinear programming (NLP) problems usually require the use of more than one optimization technique. Moreover, the interaction between the user (analysis/synthesis) program and the NLP system can lead to interface, scaling, or convergence problems. An NLP solution system is presented that seeks to solve these problems by providing a programming system to ease the user-system interface. A simple set of rules is used to select an optimization technique or to switch from one technique to another in an attempt to detect, diagnose, and solve some potential problems. Numerical examples involving finite element based optimal design of space trusses and rotor bearing systems are used to illustrate the applicability of the proposed methodology.

High-rate synthesis of Cu-BTC metal-organic frameworks.

PubMed

Kim, Ki-Joong; Li, Yong Jun; Kreider, Peter B; Chang, Chih-Hung; Wannenmacher, Nick; Thallapally, Praveen K; Ahn, Ho-Geun

2013-12-21

The reaction conditions for the synthesis of Cu-BTC (BTC = benzene-1,3,5-tricarboxylic acid) were elucidated using a continuous-flow microreactor-assisted solvothermal system to achieve crystal size and phase control. A high-rate synthesis of Cu-BTC metal-organic frameworks with a BET surface area of more than 1600 m(2) g(-1) (Langmuir surface area of more than 2000 m(2) g(-1)) and with a 97% production yield could be achieved with a total reaction time of 5 minutes.

Drug Development of the Antimalarial Agent Artemisinin: Total Synthesis, Analog Synthesis, and Structure-Activity Relationship Studies

DTIC Science & Technology

1990-08-15

16. SUPPLEMENTARY NOTATION 17 COSATi CODES FiELD 07 06 CROUP 03 01 SUB-GROUP IB SUBJECT TERMS (Cont/nu* on rtvtnt if ntctiwy *ne identity b ...number of requisite substituents resulted in the synthesis of ring cleaved analogs and partial structures of artemisinin: (+)-C/D, (+)-A/ B /C, (+)-A/C...in the preparation of the unstable aldehyde 2, and in commendable fashion others have employed an enol ether photo-oxygenation as entry to that

Total synthesis of cyclomarins A, C and D, marine cyclic peptides with interesting anti-tuberculosis and anti-malaria activities.

PubMed

Barbie, Philipp; Kazmaier, Uli

2016-07-07

Cyclomarins are cyclic heptapeptides containing four unusual amino acids. New synthetic protocols toward their synthesis have been developed, leading to the synthesis and biological evaluation of three natural occurring cyclomarins. Interestingly, cyclomarins address two completely different targets: Clp C1, a subunit of the caseinolytic protease of Mycobacterium tuberculosis (MTB), as well as PfAp3Ase of Plasmodium falciparum. Therefore, cyclomarins are interesting lead structures for the development of drugs against tuberculosis and malaria.

Approaches to the Chemical Synthesis of the Chlorosulfolipids

PubMed Central

Chung, Won-Jin; Vanderwal, Christopher D.

2014-01-01

CONSPECTUS Since the initial discovery of the chlorosulfolipids in 1969, the chemical synthesis community largely ignored these compounds for nearly four decades, perhaps because they contain a high density of chlorine atoms that suggested that these molecules and any projected synthetic intermediates might be unstable. Beginning in 2008, a sudden flurry of synthesis activity by several research groups, including our own, appeared in the literature. In this Account, we highlight our work from the last several years on the chemical synthesis of the chlorosulfolipids. Our work in this area began with attempts to stereoselectively generate the abundant dichloroalcohol functional group arrangements in these natural targets. In these early studies, we learned that many polychlorinated intermediates were far more stable than anticipated. We also developed a method for the diastereoselective dichlorination of allylic alcohol derivatives that permitted access to the syn,syn-dichloroalcohol stereotriad found in several chlorosulfolipids. Concurrently, we investigated an approach to mytilipin A that included multiple intermediates bearing β-chloroaldehyde functional group arrangements, but this route proved intractable. However, we leveraged what we had learned from this approach into our first success in this area: we synthesized danicalipin A via a route that introduced all of the polar functional groups using alkene oxidation reactions. By adapting this relatively general strategy, we completed an enantioselective synthesis of malhamensilipin A. This body of work also resulted in the full stereochemical elucidation of danicalipin A and the structural revision of malhamensilipin A. Finally, with the advent of Z-selective alkene cross metathesis, we developed a second-generation synthesis that featured this strategy in place of a poorly performing Wittig olefination that plagued our first approach. In addition to this new convergent step, we developed a reliable protocol for diastereoselective addition to highly sensitive α,β-dichloroaldehydes and a method for kinetic resolution of complex vinyl epoxides. Altogether, these advances led to a synthesis of enantioenriched mytilipin A in only eight steps. In the context of this work, we discovered a number of highly stereoselective reactions that might offer new, broadly applicable lessons in acyclic stereocontrol. Moreover, this research testifies to the stability of polychlorinated molecules and should inspire confidence in the use of aliphatic chlorides in other applications, including in discovery chemistry. PMID:24400674

Antimicrobial Activities of Silver Nanoparticles Synthesized by Using Water Extract of Arnicae anthodium.

PubMed

Dobrucka, Renata; Długaszewska, Jolanta

2015-06-01

Green synthesis of nanoparticles has gained significant importance in recent years and has become the one of the most preferred methods. Also, green synthesis of nanoparticles is valuable branch of nanotechnology. Plant extracts are eco-friendly and can be an economic option for synthesis of nanoparticles. This study presents method the synthesis of silver nanoparticles using water extract of Arnicae anthodium. Formation of silver nanoparticles was confirmed by UV-visble spectroscopy, Fourier transform infrared spectroscopy and total reflection X-ray fluorescence analysis. The morphology of the synthesized silver nanoparticles was verified by SEM-EDS. The obtained silver nanoparticles were used to study their antimicrobial activity.

Total synthesis of (+/-)-taiwaniaquinol B via a domino intramolecular friedel-crafts acylation/carbonyl alpha-tert-alkylation reaction.

PubMed

Fillion, Eric; Fishlock, Dan

2005-09-28

The first synthesis of taiwaniaquinol B, a 6-nor-5(6-->7)abeoabietane-type diterpenoid exhibiting the uncommon fused 6-5-6 tricyclic carbon skeleton, was accomplished in 15 steps. A Lewis acid-promoted tandem intramolecular Friedel-Crafts/carbonyl alpha-tert-alkylation reaction was exploited as the core strategy for the synthesis of the sterically congested 1-indanone-containing tricyclic structure. This multiple carbon-carbon bond forming reaction exploits the unique reactivity of Meldrum's acid. The facile precursor synthesis makes this a useful methodology for the expedient modification and assembly of sterically congested 1-indanone-containing ring systems.

Total Synthesis of Marine Cyclic Enol-Phosphotriester Salinipostin Compounds

NASA Astrophysics Data System (ADS)

Zhao, Mingliang; Wei, Xianfeng; Liu, Xuemeng; Dong, Xueyang; Yu, Rilei; Wan, Shengbiao; Jiang, Tao

2018-06-01

Due to their structural diversity and variety of biological activities, marine natural products have been the subject of extensive study. These compounds, especially phospholipid polycyclic aromatic hydrocarbons, have a wide range of pharmacological applications, including embedded DNA and central nervous system, anti-tumor, anti-virus, anti-parasite, anti-bacterial, and antithrombotic effects. Unfortunately, the insufficient drug sources have limited the development of these compounds. In this study, we isolated salinpostin compounds from a fermentation solution of marine-derived Salinospora sp., which has a common bicyclic enol-phosphotriester core framework, as well as potent and selective antimalarial activities against P. falciparum with EC50 = 50 nmol L-1. The chemical synthesis of these compounds in greater quantities is necessary for their use in bioactivity studies. Thus we explored a short route with high yields and mild reaction conditions, which can generate combinatorial libraries for drug discovery and lead optimization. We developed a new total synthesis method for six cyclic enol-phosphotriester salinipotin compounds and their diastereomers. For the total synthesis of cyclipostin P, we prepared cyclic enol-phosphotriester salinipostin compounds in 10 steps from a readily accessible starting material, 1,3-dihydroxyacetone, and obtained an overall yield of 1.29%. We fully characterized these compounds by proton nuclear magnetic resonance (1H-NMR), carbon-13 NMR (13C-NMR), and high-resolution mass spectrometry (HRMS) analyses, and found they coincide absolutely with the same compounds reported previously.

Drug Development Against Parasitic Diseases: Synthesis of the Antimalarial Agent Qinghaosu and Analogs.

DTIC Science & Technology

A stereoselective total synthesis of (+)- artemisinin has been improved from 18 steps to 13 steps with a resultant 12-fold increase in the overall...yield. A new class of tricyclic analogs of artemisinin has been discovered that possess good in vitro antimalarial activity. U.S. and foreign patents

Glycerine and levulinic acid: renewable co-substrates for the fermentative synthesis of short-chain poly(hydroxyalkanoate) biopolymers

USDA-ARS?s Scientific Manuscript database

Glycerine and levulinic acid were used alone and in combination for the fermentative synthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/V) biopolymers. Shake-flask cultures of Pseudomonas oleovorans NRRL B-14682 containing different glycerine:levulinic acid ratios (1%, w/v total carbon ...

The Effects of Science Instruction on Young Children's Vocabulary Learning: A Research Synthesis

ERIC Educational Resources Information Center

Guo, Ying; Wang, Shanshan; Hall, Anna H.; Breit-Smith, Allison; Busch, Jamie

2016-01-01

This article synthesized science instruction studies with preschool and kindergarten children to understand the magnitude of science instruction's impact on young children's vocabulary outcomes. A total of seven studies that met criteria for the synthesis and provided sufficient data for the calculation of effect size were included. Science…

A Review and Synthesis of Recent Research in Second Life

ERIC Educational Resources Information Center

Fang, Yu-Shen; Lee, Lung-Sheng

2009-01-01

Purpose: Applications of online Second Life (SL) prevail over the world. The purpose of this paper is to make a review and synthesis of recent research studies on SL. Design/methodology/approach: Documental analysis is employed. Totally, 135 research publications, published in 2006-2008, are reviewed and synthesized. Findings: Findings are as…

78 FR 23738 - Monsanto Company and Forage Genetics International (FGI); Availability of Petition for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

... pathway. Suppression of the CCOMT gene expression leads to lower CCOMT protein expression resulting in reduced synthesis of G lignin subunit compared to conventional alfalfa at the same stage of growth. The reduction in G lignin subunit synthesis leads to reduced accumulation of total lignin, measured as acid...

Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

PubMed

Farshidfar, Farnaz; Pinder, Mark A; Myrie, Semone B

2017-01-01

Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Harry Stack Sullivan Colloquium: George Herbert Mead and Harry Stack Sullivan: an unfinished synthesis.

PubMed

Cottrell, L S

1978-05-01

HOW DO YOU create a new self? However he may phrase this question, it is a central theoretical and practical concern of the therapist every time he confronts a client who comes to him for help. What are the processes out of which the human self emerges? However he may phrase the question, it is a central concern of the social psychologist. The obvious convergence of interests indicated by these two questions should occasion no surprise among students of Sullivan and Mead. What perhaps should be surprising is that an effective synthesis of their theories has progressed no further than it has to date. My remarks today are based on the conviction that a more adequate psychiatric theory and practice and a more complete social psychological theory and research program depend on such a synthesis. Behavioral scientists concerned with the development of a truly interactionist social psychology are, I believe, generally agreed that George Herbert Mead (1863-1931), philosopher and social psychologist, and Harry Stack Sullivan (1892-1949), psychiatrist and social psychologist, have laid conceptual foundations upon which such a discipline can be erected. Now a vast assortment of activities is tagged as social psychology and its boundaries are, indeed, difficult to draw. However, for our present purposes we can define its focus as the study of the processes and products of inter- and intrapersonal and inter- and intragoup interaction, let the boundaries fall where they will.

Synthesis of prostaglandins by conjugate addition and alkylation of a directed enolate ion. 4,5-allenyl prostaglandins

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

Patterson, J.W.

1990-09-28

Over the previous two decades many elegant syntheses of prostaglandins, which in more sophisticated forms, allow the stereospecific introduction of the various asymmetric carbons have been accomplished. However, among these approaches the cuprate addition/enolate alkylation of suitable cyclopentenone {sup 2} stands out because of brevity and convergence. The recent reports by Noyori{sup 3} and Corey{sup 4} and their colleagues have reduced to practice the conversion of 4-alkoxycyclopentenones to prostaglandin E{sub 2} (PGE{sub 2}) by conjugate addition of an organocopper derivative of the lower side chain followed by alkylation of the resulting carbanion with methyl 7-halohept-2-enoate. The subject of this papermore » is application of the Tardella tin enolate alkylation developed by Noyori to the synthesis of 4, 5-allenic prostaglandins, a pharmacologically important class of compounds. The authors results demonstrate that the tandem alkylation of an enone precursor with a cuprate reagent followed by alkylation of the corresponding tin enolate with bromide reagent is a viable synthetic method for 4,5-didehydro-PGE{sub 2}. Because the optically active forms of 1 and the vinyl iodide precursor of the PGE{sub 2} lower side chain have been employed to produce a single enantiomer of PGE{sub 2}, the extension of the methodology described here to the synthesis of single enantiomers of 4a awaits only the preparation of the separate enantiomers of allene 14.« less

Functional Specialization of Cellulose Synthase Isoforms in a Moss Shows Parallels with Seed Plants1[OPEN

PubMed Central

Li, Xingxing; Huang, Shixin; Van de Meene, Allison M.L.; Tran, Mai L.; Killeavy, Erin; Mercure, Danielle; Burton, Rachel A.

2017-01-01

The secondary cell walls of tracheary elements and fibers are rich in cellulose microfibrils that are helically oriented and laterally aggregated. Support cells within the leaf midribs of mosses deposit cellulose-rich secondary cell walls, but their biosynthesis and microfibril organization have not been examined. Although the Cellulose Synthase (CESA) gene families of mosses and seed plants diversified independently, CESA knockout analysis in the moss Physcomitrella patens revealed parallels with Arabidopsis (Arabidopsis thaliana) in CESA functional specialization, with roles for both subfunctionalization and neofunctionalization. The similarities include regulatory uncoupling of the CESAs that synthesize primary and secondary cell walls, a requirement for two or more functionally distinct CESA isoforms for secondary cell wall synthesis, interchangeability of some primary and secondary CESAs, and some CESA redundancy. The cellulose-deficient midribs of ppcesa3/8 knockouts provided negative controls for the structural characterization of stereid secondary cell walls in wild type P. patens. Sum frequency generation spectra collected from midribs were consistent with cellulose microfibril aggregation, and polarization microscopy revealed helical microfibril orientation only in wild type leaves. Thus, stereid secondary walls are structurally distinct from primary cell walls, and they share structural characteristics with the secondary walls of tracheary elements and fibers. We propose a mechanism for the convergent evolution of secondary walls in which the deposition of aggregated and helically oriented microfibrils is coupled to rapid and highly localized cellulose synthesis enabled by regulatory uncoupling from primary wall synthesis. PMID:28768816

The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

PubMed Central

Stellaard, Frans

2017-01-01

The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded. PMID:28321334

Knowledge synthesis methods for integrating qualitative and quantitative data: a scoping review reveals poor operationalization of the methodological steps.

PubMed

Tricco, Andrea C; Antony, Jesmin; Soobiah, Charlene; Kastner, Monika; MacDonald, Heather; Cogo, Elise; Lillie, Erin; Tran, Judy; Straus, Sharon E

2016-05-01

To describe and compare, through a scoping review, emerging knowledge synthesis methods for integrating qualitative and quantitative evidence in health care, in terms of expertise required, similarities, differences, strengths, limitations, and steps involved in using the methods. Electronic databases (e.g., MEDLINE) were searched, and two reviewers independently selected studies and abstracted data for qualitative analysis. In total, 121 articles reporting seven knowledge synthesis methods (critical interpretive synthesis, integrative review, meta-narrative review, meta-summary, mixed studies review, narrative synthesis, and realist review) were included after screening of 17,962 citations and 1,010 full-text articles. Common similarities among methods related to the entire synthesis process, while common differences related to the research question and eligibility criteria. The most common strength was a comprehensive synthesis providing rich contextual data, whereas the most common weakness was a highly subjective method that was not reproducible. For critical interpretive synthesis, meta-narrative review, meta-summary, and narrative synthesis, guidance was not provided for some steps of the review process. Some of the knowledge synthesis methods provided guidance on all steps, whereas other methods were missing guidance on the synthesis process. Further work is needed to clarify these emerging knowledge synthesis methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of surfactants and natural detergents on phosphatidylcholine synthesis in photoreceptor membranes.

PubMed

Roque, M E; Castagnet, P I; Giusto, N M

2001-07-01

The synthesis of phosphatidylcholine (PC) in rod outer segments (ROS) catalysed by lysophosphatidylcholine acyltransferase and phosphatidylethanolamine N-methyltransferase (PE N-MTase) was studied and the effects of natural (FA and lysophospholipids) and synthetic (Triton X-100, deoxycholate and CHAPS) surfactants was evaluated. In all experimental conditions used, incorporation of labelled oleate into lysophosphatidylcholine (lysoPC) was at least 40 times greater than oleate incorporation into any other lysophospholipid. Acylation of lysoPC was slightly affected by Triton X-100 and was totally inhibited in the presence of 10 mM sodium deoxycholate (NaDOC) or CHAPS. Below their critical micelle concentration (cmc) Triton X-100 and NaDOC stimulated acylation of all ROS lysophospholipids analysed. The activity of PE N-MTase was stimulated at detergent concentrations below the cmc and inhibited at concentrations above the cmc for all three detergents tested. The effect of FA with differing degree of unsaturation on PC synthesis was evaluated. Oleic acid (10 microM) inhibited methyl group incorporation into total PC, whereas from 100 microM onward, the methylating activity increased with preferential synthesis of PC. Docosahexaenoic acid, in turn, inhibited PE N-MTase activity at every concentration tested. These results suggest that PC synthesis in ROS membranes is modified by bioregulators and surfactants altering the physico-chemical state of the membrane.

Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats

NASA Technical Reports Server (NTRS)

Yoshida, S.; Leskiw, M. J.; Schluter, M. D.; Bush, K. T.; Nagele, R. G.; Lanza-Jacoby, S.; Stein, T. P.

1992-01-01

The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.

Synthesis and degradation of phenylalanine ammonia-lyase of Rhodosporidium toruloides.

PubMed Central

Gilbert, H J; Tully, M

1982-01-01

The regulation of the enzyme phenylalanine ammonia-lyase (PAL), which is of potential use in oral treatment of phenylketonuria, was investigated. Antiserum against PAL was prepared and was shown to be monospecific for the enzyme by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native enzyme and two inactive mutant forms of the enzyme were purified to homogeneity by immunoaffinity chromatography, using anti-PAL immunoglobulin G-Sepharose 4B. Both mutant enzymes contained intact prosthetic groups. The formation of PAL catalytic activity after phenylalanine was added to yeast cultures was paralleled by the appearance of enzyme antigen. During induction, uptake of [3H]leucine into the enzyme was higher than uptake into total protein. Our results are consistent with de novo synthesis of an enzyme induced by phenylalanine, rather than activation of a proenzyme. The half-lives of PAL and total protein were similar in both exponential and stationary phase cultures. No metabolite tested affected the rate of enzyme degradation. Glucose repressed enzyme synthesis, whereas ammonia reduced phenylalanine uptake and pool size and so may repress enzyme synthesis through inducer exclusion. The synthesis of enzyme antigen by a mutant unable to metabolize phenylalanine indicated that this amino acid is the physiological inducer of the enzyme. PMID:7068528

Using genetic algorithms with subjective input from human subjects: implications for fitting hearing aids and cochlear implants.

PubMed

Başkent, Deniz; Eiler, Cheryl L; Edwards, Brent

2007-06-01

To present a comprehensive analysis of the feasibility of genetic algorithms (GA) for finding the best fit of hearing aids or cochlear implants for individual users in clinical or research settings, where the algorithm is solely driven by subjective human input. Due to varying pathology, the best settings of an auditory device differ for each user. It is also likely that listening preferences vary at the same time. The settings of a device customized for a particular user can only be evaluated by the user. When optimization algorithms are used for fitting purposes, this situation poses a difficulty for a systematic and quantitative evaluation of the suitability of the fitting parameters produced by the algorithm. In the present study, an artificial listening environment was generated by distorting speech using a noiseband vocoder. The settings produced by the GA for this listening problem could objectively be evaluated by measuring speech recognition and comparing the performance to the best vocoder condition where speech was least distorted. Nine normal-hearing subjects participated in the study. The parameters to be optimized were the number of vocoder channels, the shift between the input frequency range and the synthesis frequency range, and the compression-expansion of the input frequency range over the synthesis frequency range. The subjects listened to pairs of sentences processed with the vocoder, and entered a preference for the sentence with better intelligibility. The GA modified the solutions iteratively according to the subject preferences. The program converged when the user ranked the same set of parameters as the best in three consecutive steps. The results produced by the GA were analyzed for quality by measuring speech intelligibility, for test-retest reliability by running the GA three times with each subject, and for convergence properties. Speech recognition scores averaged across subjects were similar for the best vocoder solution and for the solutions produced by the GA. The average number of iterations was 8 and the average convergence time was 25.5 minutes. The settings produced by different GA runs for the same subject were slightly different; however, speech recognition scores measured with these settings were similar. Individual data from subjects showed that in each run, a small number of GA solutions produced poorer speech intelligibility than for the best setting. This was probably a result of the combination of the inherent randomness of the GA, the convergence criterion used in the present study, and possible errors that the users might have made during the paired comparisons. On the other hand, the effect of these errors was probably small compared to the other two factors, as a comparison between subjective preferences and objective measures showed that for many subjects the two were in good agreement. The results showed that the GA was able to produce good solutions by using listener preferences in a relatively short time. For practical applications, the program can be made more robust by running the GA twice or by not using an automatic stopping criterion, and it can be made faster by optimizing the number of the paired comparisons completed in each iteration.

Alternative sampling designs and estimators for annual surveys

Treesearch

Paul C. Van Deusen

2000-01-01

Annual forest inventory systems in the United States have generally converged on sampling designs that: (1) measure equal proportions of the total number of plots each year; and (2) call for the plots to be systematically dispersed. However, there will inevitably be a need to deviate from the basic design to respond to special requests, natural disasters, and budgetary...

77 FR 24943 - Fall Creek Hydro, LLC; Notice of Application Accepted for Filing, Soliciting Motions To Intervene...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

...) a 26-foot-long penstock convergence and trifurcation section leading to two Francis and one Kaplan turbine-generating units with a total installed capacity of 10 megawatts (MW); (10) a 75-foot- long, 60...-wide concrete tailrace channel equipped with picket barrier to prevent fish from accessing the turbine...

Theory of Mind and the Brain in Anorexia Nervosa: Relation to Treatment Outcome

ERIC Educational Resources Information Center

Schulte-Ruther, Martin; Mainz, Verena; Fink, Gereon R.; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2012-01-01

Objective: Converging evidence suggests deficits in theory-of-mind (ToM) processing in patients with anorexia nervosa (AN). The present study aimed at elucidating the neural mechanisms underlying ToM-deficits in AN. Method: A total of 19 adolescent patients with AN and 21 age-matched controls were investigated using functional magnetic resonance…

Alternatives for jet engine control

NASA Technical Reports Server (NTRS)

Sain, M. K.; Yurkovich, S.; Hill, J. P.; Kingler, T. A.

1983-01-01

The development of models of tensor type for a digital simulation of the quiet, clean safe engine (QCSE) gas turbine engine; the extension, to nonlinear multivariate control system design, of the concepts of total synthesis which trace their roots back to certain early investigations under this grant; the role of series descriptions as they relate to questions of scheduling in the control of gas turbine engines; the development of computer-aided design software for tensor modeling calculations; further enhancement of the softwares for linear total synthesis, mentioned above; and calculation of the first known examples using tensors for nonlinear feedback control are discussed.

Total Synthesis of Plakilactones C, B and des-Hydroxyplakilactone B by the Oxidative Cleavage of Gracilioether Furanylidenes.

PubMed

Norris, Matthew D; Perkins, Michael V

2016-08-05

A chemoselective oxidative cleavage of synthetic gracilioether B, 11-epi-gracilioether C benzoate, and des-hydroxygracilioether C with pyridinium chlorochromate, which proceeds with loss of the furanyl acetate, has enabled total synthesis and stereochemical elucidation of the marine sponge metabolites (4R,6R)-plakilactone C, (4R,6R,9R)-plakilactone B, and (4R,6R)-des-hydroxyplakilactone B. des-Hydroxygracilioether C, the putative biosynthetic precursor to hippolachnin A, was also found to undergo a facile ene cyclization on treatment with SnCl4.

Total synthesis and biological investigation of (-)-promysalin.

PubMed

Steele, Andrew D; Knouse, Kyle W; Keohane, Colleen E; Wuest, William M

2015-06-17

Compounds that specifically target pathogenic bacteria are greatly needed, and identifying the method by which they act would provide new avenues of treatment. Herein we report the concise, high-yielding total synthesis (eight steps, 35% yield) of promysalin, a natural product that displays antivirulence phenotypes against pathogenic bacteria. Guided by bioinformatics, four diastereomers were synthesized, and the relative and absolute stereochemistries were confirmed by spectral and biological analysis. Finally, we show for the first time that promysalin displays two antivirulence phenotypes: the dispersion of mature biofilms and the inhibition of pyoverdine production, hinting at a unique pathogenic-specific mechanism of action.

Synthesis of racemic β-chamigrene, a spiro[5.5]undecane sequiterpene.

PubMed

Antonsen, Simen; Skattebøl, Lars; Stenstrøm, Yngve

2014-12-10

The present paper describes a total synthesis of racemic β-chamigrene, a sesquiterpene with a spiro[5.5]undecane carbon framework. Compared with previously reported β-chamigrene syntheses, we were able to reduce the total number of reaction steps, which also resulted in a significant improvement of the overall yield. The commercially available ketone 6-methylhept-5-en-2-one was transformed by known simple procedures into 3,3-dimethyl-2-methylenecyclohexanone. This reacted with isoprene by a Diels-Alder reaction to give a spiro ketone. An olefination reaction on this compound gave the target molecule.

Facile total synthesis and antimicrobial activity of the marine fatty acids (Z)-2-methoxy-5-hexadecenoic acid and (Z)-2-methoxy-6-hexadecenoic acid.

PubMed

Carballeira, N M; Emiliano, A; Hernández-Alonso, N; González, F A

1998-12-01

The total synthesis of the naturally occurring (Z)-2-methoxy-5-hexadecenoic acid and (Z)-2-methoxy-6-hexadecenoic acid was accomplished using as a key step Mukaiyama's trimethylsilyl cyanide addition to 4- and 5-pentadecenal, respectively. These syntheses further confirm the structures of the natural marine fatty acids and corroborate their cis double-bond stereochemistry. The title compounds were antimicrobial against the Gram-positive bacteria Staphylococcus aureus (MIC 0.35 micromol/mL) and Streptococcus faecalis (MIC 0.35 micromol/mL).