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Palladium-catalyzed oxidative annulations between phenols and alkenylcarboxylic acids produced a library of benzofuran compounds. Depending on the nature of the substitution of the phenol precursor, either 2,3-dialkylbenzofurans or 2-alkyl-3-methylene-2,3-dihydrobenzofurans can be synthesized with excellent regioselectivity. Reactions between conjugated 5-phenylpenta-2,4-dienoic acids and phenol gave 3-alkylidenedihydrobenzofuran alkaloid motifs while biologically active 7-arylbenzofuran derivatives were prepared by starting from 2-phenylphenols. More interestingly, selective incorporation of deuterium from D2O has been discovered, which offers an attractive one-step method to access deuterated compounds.
This thesis is focused on two main areas of organic synthesis, palladium-catalyzed functionalization of alkenes and allylic alcohols, as well as development of new allylboration reactions.
We have developed a palladium-catalyzed selective allylic trifluoroacetoxylation reaction based on C−H functionalization. Allylic trifluoroacetates were synthesized from functionalized olefins under oxidative conditions. The reactions proceed under mild conditions with a high level of diastereoselectivity. Mechanistic studies of the allylic C−H trifluoroacetoxylation indicate that the reaction proceeds via (η3-allyl)palladium(IV) intermediate.
Palladium-catalyzed regio- and stereoselective synthesis of allylboronic acids from allylic alcohols has been demonstrated. Diboronic acid B2(OH)4 was used as the boron source in this process.
The reactivity of the allylboronic acids were studied in three types of allylboration reactions: allylboration of ketones, imines and acyl hydrazones. All three processes are conducted under mild conditions without any additives. The reactions proceeded with remarkably high regio- and stereoselectivity.
An asymmetric version of the allylboration of ketones was also developed. In this process chiral BINOL derivatives were used as catalysts. The reaction using γ-disubstituted allylboronic acids and various aromatic and aliphatic ketones afforded homoallylic alcohols bearing two adjacent quaternary stereocenters with excellent regio-, diastereo- and enantioselectivity (up to 97:3 er) in high yield. The stereoselectivity in the allylboration reactions could be rationalized on the basis of the Zimmerman-Traxler TS model.
Allylboration of ketones with gamma-disubstituted allylboronic acids is performed in the presence of chiral BINOL derivatives. The reaction is suitable for single-step creation of adjacent quaternary stereocenters with high selectivity. We show that, with an appropriate choice of the chiral catalyst and the stereoisomeric prenyl substrate, full control of the stereo- and enantioselectivity is possible in the reaction.
The hexacoordinate complexes that the macrobicyclic ligands {(NH3)(2)sar)(2+) and {NMe3)(2)sar}(2+) (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) form with transition metals such as Co-III, Co-II and Cu-II can adopt several isomeric structures. In this article, we have firstly employed DFT methods lo compute the relative stability of their Delta-ob(3), Delta-ob(2)lel, Delta-lel(2)ob and Delta-lel(3) isomers, as well as the activation barriers for their interconversion. In agreement with the experimental data, the results show that, in general, the different isomers of the Co-III and Co-II complexes present similar free energies, whereas the Cu-II complexes show a strong tendency towards the lel(3) form. In addition, the interplay between the structure and stability of these species has been studied by combining shape maps with a distortion/interaction energy analysis. In contrast to the geometries close to the ideal octahedron that all the studied Co complexes present, the le)3 structures of [Cu{(NH3)(2)sar}](4+) and [Cu{(NMe3)(2)sar](4+) are better described. as trigonal prisms. In such structures the ligand adopts a conformation significantly more stable than in the other isomers, and this drives the formation of lel(3)-[Cu{(NH3)(2)sar}](4+) and lel(3)-[Cu{(NNe3)(2)sar}](4+). Overall, the results show a clear relationship between the stability of a given isomer and its degree of distortion with respect to the ideal octahedron (or trigonal prism), with the latter being ultimately dependent on the transition metal and its radius.
Empirical force fields for computer simulations of carbohydrates are often implicitly assumed to be valid also at temperatures different from room temperature for which they were optimited: Herein, the temperature dependence of the hydroxymethyl group rotamer populations in short oligogaccharides is invegtigated using Molecular dynamics simulations and NMR spectroscopy. Two oligosaccharides, methyl beta-cellobioside and beta-cellotetraose were simulated using three different carbohydrate force fields (CHARMM C35, GLYCAM06, and GROMOS 56A(carbo)) in combination with different water models (SPC, SPC/E, and TIP3P) using replica exchange molecular dynamics simulations. For comparison, hydroxymethyl group rotamer populations were investigated for methyl beta-cellobioside and cellopentaose based- on measured NMR (3)J(H5,H6) coupling constants, in the latter case by using a chemical shift selective NMR-filter. Molecular dynamics simulations in combination with NMR spectroscopy show that the temperature dependence of the hydroxymethyl rotamer population in these short cellooligomers, in the range 263-344 K, generally becomes exaggerated in simulations when compared to experimental data, but also that it is dependent on simulation conditions, and most notably properties of the water model.
The mechanism of the N-alkylation of amines with alcohols catalyzed by an iridium complex containing an N-heterocyclic carbene (NHC) ligand with a tethered alcohol/alkoxide functionality was investigated by a combination of experimental and computational methods. The catalyst resting state is an iridium hydride species containing the amine substrate as a ligand, and decoordination of the amine, followed by coordination of the imine intermediate to the iridium center, constitute the rate-determining step (rds) of the catalytic process. The alcohol/alkoxide that is tethered to the NHC participates in every step of the catalytic cycle by accepting or releasing protons and forming hydrogen bonds with the reacting species. Thus, the iridium complex with the alcohol/alkoxide tethered to the N-heterocyclic carbene ligand acts as a bifunctional catalyst.
A lab-on-a-chip traveling wave magnetophoresis approach for sensitive and rapid protein detection is reported. In this method, a chip-based magnetic microarray comprising lines of micrometer-sized thin film magnetic elements was used to control the movement of magnetic beads (MBs). The MBs and the chip were functionalized, forming a sandwich-type assay. The MBs were transported across a detection area, and the presence of target molecules resulted in the immobilization of MBs within this area. Target quantification was accomplished by MB counting in the detection area using an optical microscope. In order to demonstrate the versatility of the microarray, biotinylated antiavidin was selected as the target protein. In this case, avidin-functionalized MBs and an avidin-functionalized detection area were used. With a total assay time of 1 to 1.5 h (depending on the labeling approach used), a limit of detection in the attomole range was achieved. Compared to on-chip surface plasmon resonance biodetection systems, our method has a larger dynamic range and is about a factor of 500 times more sensitive. Furthermore, our MB transportation system can operate in any chip-based biosensor platform, thereby significantly improving traditional biosensors.
This study identifies a series of Ir-bicyclic phosphoroamidite-oxazoline/thiazole catalytic systems that can hydrogenate a wide range of minimally functionalized olefins (including E-and Z-tri- and disubstituted substrates, vinylsilanes, enol phosphinates, tri- and disubstituted alkenylboronic esters, and alpha,beta-unsaturated enones) in high enantioselectivities (ee values up to 99%) and conversions. The design of the new phosphoroamidite-oxazoline/thiazole ligands derives from a previous successful generation of bicyclic N-phosphane-oxazoline/thiazole ligands, by replacing the N-phosphane group with a pi-acceptor biaryl phosphoroamidite moiety. A small but structurally important family of Ir-phosphoroamidite-oxazoline/thiazole precatalysts has thus been synthesized by changing the nature of the N-donor group (either oxazoline or thiazole) and the configuration at the biaryl phosphoroamidite moiety. The substitution of the N-phosphane by a phosphoroamidite group in the bicyclic N-phosphane-oxazoline/thiazole ligands extended the range of olefins that can be successfully hydrogenated.
Three different enzymes are discussed, cytochrome c oxidase, involved in aerobic respiration, cytochrome c dependent nitric oxide reductase, involved in denitrification (anaerobic respiration), and photosystem II, involved in photosynthesis. For all three systems, free energy profiles for the entire catalytic cycle are obtained from quantum mechanical calculations on large cluster models of the active sites, using hybrid density functional theory with the B3LYP* functional. The free energy pro-files are used to solve different fundamental problems concerning energy conservation, enzymatic reaction mechanisms and structure, and also to explain experimental results that seem to be in conflict with each other. Possible future applications to related problems using similar methodology are suggested.
Experiments have shown that the A-family cytochrome c oxidases pump four protons per oxygen molecule, also at a high electrochemical gradient. This has been considered a puzzle, since two of the reduction potentials involved, Cu(II) and Fe(III), were estimated from experiments to be too low to afford proton pumping at a high gradient The present quantum mechanical study (using hybrid density functional theory) suggests a solution to this puzzle. First, the calculations show that the charge compensated Cu(II) potential for Cu-B is actually much higher than estimated from experiment, of the same order as the reduction potentials for the tyrosyl radical and the ferryl group, which are also involved in the catalytic cycle. The reason for the discrepancy between theory and experiment is the very large uncertainty in the experimental observations used to estimate the equilibrium potentials, mainly caused by the lack of methods for direct determination of reduced Cu-B. Second, the calculations show that a high energy metastable state, labeled E-H, is involved during catalytic turnover. The E-H state mixes the low reduction potential of Fe(III) in heme a(3) with another, higher potential, here suggested to be that of the tyrosyl radical, resulting in enough exergonicity to allow proton pumping at a high gradient In contrast, the corresponding metastable oxidized state, O-H, is not significantly higher in energy than the resting state, O. Finally, to secure the involvement of the high energy E-H state it is suggested that only one proton is taken up via the K-channel during catalytic turnover.
One of the remaining mysteries regarding the respiratory enzyme cytochrome c oxidase is how proton pumping can occur in all reduction steps in spite of the low reduction potentials observed in equilibrium titration experiments for two of the active site cofactors, CUB(II) and Fe-a3(III). It has been speculated that, at least the copper cofactor can acquire two different states, one metastable activated state occurring during enzyme turnover, and one relaxed state with lower energy, reached only when the supply of electrons stops. The activated state should have a transiently increased Cu-B(II) reduction potential, allowing proton pumping. The relaxed state should have a lower reduction potential, as measured in the titration experiments. However, the structures of these two states are not known. Quantum mechanical calculations show that the proton coupled reduction potential for Cu-B is inherently high in the active site as it appears after reaction with oxygen, which explains the observed proton pumping. It is suggested here that, when the flow of electrons ceases, a relaxed resting state is formed by the uptake of one extra proton, on top of the charge compensating protons delivered in each reduction step. The extra proton in the active site decreases the proton coupled reduction potential for Cu-B by almost half a volt, leading to agreement with titration experiments. Furthermore, the structure for the resting state with an extra proton is found to have a hydroxo-bridge between Cu-B(II) and Fe-a3(III), yielding a magnetic coupling that can explain the experimentally observed EPR silence.
A structurally diverse range of chiral diaryliodonium salts have been synthesised which have potential application in metal-free stereoselective arylation reactions.
The hydroxyl group of enantioenriched benzyl, propargyl, allyl, and alkyl alcohols has been intramolecularly displaced by uncharged O-, N-, and S-centered nucleophiles to yield enantioenriched tetrahydrofuran, pyrrolidine, and tetrahydrothiophene derivatives with phosphinic acid catalysis. The five-membered heterocyclic products are generated in good to excellent yields, with high degree of chirality transfer, and water as the only side-product. Racemization experiments show that phosphinic acid does not promote S(N)1 reactivity. Density functional theory calculations corroborate a reaction pathway where the phosphinic acid operates as a bifunctional catalyst in the intramolecular substitution reaction. In this mechanism, the acidic proton of the phosphinic acid protonates the hydroxyl group, enhancing the leaving group ability. Simultaneously, the oxo group of phosphinic acid operates as a base abstracting the nucleophilic proton and thus enhancing the nucleophilicity. This reaction will open up new atom efficient techniques that enable alcohols to be used as nucleofuges in substitution reactions in the future.
Whereas the cluster [Mo3S4(acac)(3)(py)(3)](+) ([1](+), acac=acetylacetonate, py=pyridine) reacts with a variety of alkynes, the cluster [W3S4(acac)(3)(py)(3)](+) ([2](+)) remains unaffected under the same conditions. The reactions of cluster [1]+ show polyphasic kinetics, and in all cases clusters bearing a bridging dithiolene moiety are formed in the first step through the concerted [3+2] cycloaddition between the C equivalent to C atoms of the alkyne and a Mo(mu-S)(2) moiety of the cluster. A computational study has been conducted to analyze the effect of the metal on these concerted [3+ 2] cycloaddition reactions. The calculations suggest that the reactions of cluster [2](+) with alkynes feature Delta G(+) values only slightly larger than its molybdenum analogue, however, the differences in the reaction free energies between both metal clusters and the same alkyne reach up to approximately 10 kcal mol(-1), therefore indicating that the differences in the reactivity are essentially thermodynamic. The activation strain model (ASM) has been used to get more insights into the critical effect of the metal center in these cycloadditions, and the results reveal that the change in reactivity is entirely explained on the basis of the differences in the interaction energies E-int between the cluster and the alkyne. Further decomposition of the E-int values through the localized molecular orbital-energy decomposition analysis (LMO-EDA) indicates that substitution of the Mo atoms in cluster [1](+) by W induces changes in the electronic structure of the cluster that result in weaker intra-and inter-fragment orbital interactions.
A new iridium N-heterocyclic carbene (NHC) metallolinker has been synthesised and introduced into a metal-organic framework (MOF), for the first time, via two different routes: direct synthesis and postsynthetic exchange (PSE). The two materials were compared in terms of the Ir loading and distribution using X-ray energy dispersive spectroscopy (EDS), the local Ir structure using X-ray absorption spectroscopy (XAS) and the catalytic activity. The materials showed good activity and recyclability as catalysts for the isomerisation of an allylic alcohol.
The chemical stability of metal-organic frameworks (MOFs) is a major factor preventing their use in industrial processes. Herein, it is shown that judicious choice of the base for the Suzuki-Miyaura cross-coupling reaction can avoid decomposition of the MOF catalyst Pd@MIL-101-NH2(Cr). Four bases were compared for the reaction: K2CO3, KF, Cs2CO3 and CsF. The carbonates were the most active and achieved excellent yields in shorter reaction times than the fluorides. However, powder XRD and N-2 sorption measurements showed that the MOF catalyst was degraded when carbonates were used but remained crystalline and porous with the fluorides. XANES measurements revealed that the trimeric chromium cluster of Pd@MIL-101-NH2(Cr) is still present in the degraded MOF. In addition, the different countercations of the base significantly affected the catalytic activity of the material. TEM revealed that after several catalytic runs many of the Pd nanoparticles (NPs) had migrated to the external surface of the MOF particles and formed larger aggregates. The Pd NPs were larger after catalysis with caesium bases compared to potassium bases.
Copper-catalyzed cross-coupling of substituted allylboronic acids with alpha-diazoketones was studied. This allylation reaction is highly regioselective, providing the branched allylic product. The process involves creation of a new C(sp(3))-C(sp(3)) bond by retaining the keto functional group of the alpha-diazoketone precursor.
Phosphoesterases are a class of enzymes that catalyze hydrolysis of phosphoester bonds. They facilitate the modification of nucleic acid sequences, as well as the breakdown of rest products of warfare agents and insecticides. In this thesis, three biomimetic complexes that perform the same tasks are studied using density functional theory.
Two of the catalysts contain a dizinc core while the third binds an Fe(III) ion and a Mn(II)ion. These complexes catalyze the hydrolysis of the phosphodiester substrate bis-(2,4)-dinitrophenyl phosphate (BDNPP). The substrate is analogous to the phosphoric link between two nucleotides in DNA, and the system is thus a model for cleaving bonds between nucleotides.
By means of computational modelling, the reaction mechanisms are investigated in detail. Different binding modes of the substrates to the catalysts are considered and several mechanistic proposals are evaluated. Conclusions are drawn on the basis of free energy barriers calculated for the different mechanisms.
In all studied reactions, a hydroxide bridging the metals becomes terminally coordinated to one of the zinc ions and then attacks the phosphorus center in a nucleophilic fashion. Leaving group dissociation takes place without a barrier.
One of the catalysts was also studied binding a model substrate for RNA, namely hydroxy-2-isopropyl p-nitrophenyl phosphate (HPNP). The hydroxide was found to act as a base, activating the alcohol moiety of the substrate which in turn performs the nucleophilic attack on the phosphorus center.
Common for all studied systems is that the catalyst-product complex is calculated to be the most stable species. Hence, this complex is suggested to be the resting state of the catalytic cycle. The free energy barriers of the reactions are associated with going from the catalystproduct complex of one catalytic cycle to the transition state for nucleophilic attack in the next. Calculated barriers are in good agreements with experiments.
Allylboronates undergo C-H allylation of unsubstituted or monosubstituted benzoquinone and naphthoquinone substrates. In the case of 2,5- or 2,6-disubstituted quinones addition involving the substituted carbon takes place. Allylation with stereodefined allylboronates occurs with retention of the configuration.
An efficient, mild, and metal-free arylation of nitro-alkanes with diaryliodonium salts has been developed, giving easy access to tertiary nitro compounds. The reaction proceeds in high yields without the need for excess reagents and can be extended to alpha-arylation of nitroesters. Nitroalkanes were selectively C-arylated in the presence of other easily arylated functional groups, such as phenols and aliphatic alcohols.
ω-Transaminases are valuable tools in biocatalysis due to their stereospecificity and their broad substrate range. In the present study, the reaction mechanism of Chromobacterium violaceum ω-transaminase is investigated by means of density functional theory calculations. A large active site model is designed based on the recent X-ray crystal structure. The detailed energy profile for the half-transamination of (S)-1-phenylethylamine to acetophenone is calculated and the involved transition states and intermediates are characterized. The model suggests that the amino substrate forms an external aldimine with the coenzyme pyridoxal-5′-phosphate (PLP), through geminal diamine intermediates. The external aldimine is then deprotonated in the rate-determining step, forming a planar quinonoid intermediate. A ketimine is then formed, after which a hemiaminal is produced by the addition of water. Subsequently, the ketone product is obtained together with pyridoxamine-5′-phosphate (PMP). In the studied half-transamination reaction the ketone product is kinetically favored. The mechanism presented here will be valuable to enhance rational and semi-rational design of engineered enzyme variants in the development of ω-transaminase chemistry.
Carbohydrates are essential biomolecules that decorate cell membranes and proteins in organisms. They are important both as structural elements and as identification markers. Many biological and pathogenic processes rely on the identification of carbohydrates by proteins, thereby making them attractive as molecular blueprints for drugs. This thesis describes how NMR spectroscopy can be utilized to study carbohydrates in solution at a molecular level. This versatile technique facilitates for investigations of (i) shapes, (ii) motions and (iii) interactions.
A conformational study of an E. coli O-antigen was performed by calculating atomic distances from NMR NOESY experiments. The acquired data was utilized to validate MD simulations of the LPS embedded in a membrane. The agreement between experimental and calculated data was good and deviations were proven to arise from spin-diffusion. In another study presented herein, both the conformation and the dynamic behavior of amide side-chains linked to derivatives of D-Fucp3N, a sugar found in the O-antigen of bacteria, were investigated. J-couplings facilitated a conformational analysis and 13C saturation transfer NMR experiments were utilized to measure rate constants of amide cis-trans isomerizations.
13C NMR relaxation and 1H PFG diffusion measurements were carried out to explore and describe the molecular motion of mannofullerenes. The dominating motions of the mannofullerene spectral density were found to be related to pulsating motions of the linkers rather than global rotational diffusion. The promising inhibition of Ebola viruses identified for a larger mannofullerene can thus be explained by an efficient rebinding mechanism that arises from the observed flexibility in the linker.
Molecular interactions between sugars and caffeine in water were studied by monitoring chemical shift displacements in titrations. The magnitude of the chemical shift displacements indicate that the binding occurs by a face to face stacking of the aromatic plane of caffeine to the ring plane of the sugar, and that the interaction is at least partly driven by solvation effects. Also, the binding of a Shigella flexneri serotype Y octasaccharide to a bacteriophage Sf6 tail spike protein was investigated. This interaction was studied by 1H STD NMR and trNOESY experiments. A quantitative analysis of the STD data was performed employing a newly developed method, CORCEMA-ST-CSD, that is able to simulate STD data more accurately since the line broadening of protein resonances are accounted for in the calculations.
Glycofullerenes, in which carbohydrate molecules are attached via a linker to a [60]fullerene core, facilitate spherical presentation of glyco-based epitopes. We herein investigate the dynamics of two glycofullerenes, having 12 and 36 mannose residues at their periphery, by NMR translational diffusion and quantitative C-13 relaxation studies employing a model-free approach for their interpretation. The sugar residues are shown to be highly flexible entities with S-2 < 0.2 in both compounds. Notably, the larger glycofullerene with longer linkers shows faster internal dynamics and higher flexibility than its smaller counterpart. The dynamics and flexibility as well as the slower translational diffusion of the larger glycofullerene, thereby favoring rebinding to a receptor, may together with its spatial extension explain why it is better than the smaller one at blocking the DC-SIGN receptor and inhibiting the infection by pseudotyped Ebola virus particles.
A versatile approach for the production of dispersed thiol-stabilized gold nanoparticles in the pores of siliceous mesocellular foam (MCF) is described. The reported method is based on an electrochemical oxidation of a gold surface generating oxidative Au-III species, which give rise to a surface-confined redox reaction yielding MCF-supported Au-I thiolates. By reducing the corresponding Au-I-S-MCF species with sodium borohydride, thiol-stabilized gold nanoparticles in the size range of 1-8 nm were obtained as determined by transmission electron microscopy. Elemental analysis indicated an Au loading of 3% (w/w) on the MCF. The surface-confined Au nanoparticles were used to catalyze the cycloisomerization of alkynoic acids to the corresponding -alkylidene lactones in high efficiency and complete 5-exo-dig selectivity under mild reaction conditions.
Some lactic acid bacteria, such as those of the Lactobacillus genus, have the ability to produce exopolysaccharides (EPSs) that confer favorable physicochemical properties to food and/or beneficial physiological effects on human health. In particular, the EPS of Lactobacillus plantarum C88 has recently demonstrated in vitro antioxidant activity and, herein, its structure has been investigated using NMR spectroscopy and the computer program CASPER (Computer Assisted Spectrum Evaluation of Regular polysaccharides). The pentasaccharide repeating unit of the O-deacetylated EPS consists of a trisaccharide backbone, -> 4)-alpha-DGalp-(1 -> 2)-alpha-D-Glcp-(1 -> 3)-beta-D-Glcp-(1 ->, with terminal D-Glc and D-Gal residues (1.0 and 0.8 equiv per repeating unit, respectively) extending from O3 and O6, respectively, of the -> 4)-alpha-D-Galp-(1 -> residue. In the native EPS an O-acetyl group is present, 0.85 equiv per repeating unit, at O2 of the alpha-linked galactose residue; thus the repeating unit of the EPS has the following structure: -> 4)[beta-D-Glcp-(1 -> 3)][beta-D-Galp-(1 -> 6)]alpha-D-Galp2Ac-(1 -> 2)-alpha-D-Glcp-(1 -> 3)-beta-D-Glcp-(1 ->. These structural features, and the chain length (similar to 10(3) repeating units on average, determined in a previous study), are expected to play an important role in defining the physicochemical properties of the polymer.
Shiga-toxin-producing Escherichia coli (STEC) is an important pathogen associated to food-borne infection in humans; strains of E.coli O181, isolated from human cases of diarrhea, have been classified as belonging to this pathotype. Herein, the structure of the O-antigen polysaccharide (PS) from E.coli O181 has been investigated. The sugar analysis showed quinovosamine (QuiN), glucosamine (GlcN), galactosamine (GalN), and glucose (Glc) as major components. Analysis of the high-resolution mass spectrum of the oligosaccharide (OS), obtained by dephosphorylation of the O-deacetylated PS with aqueous 48% hydrofluoric acid, revealed a pentasaccharide composed of two QuiNAc, one GlcNAc, one GalNAc, and one Glc residue. The H-1 and (CNMR)-C-13 chemical shift assignments of the OS were carried out using 1D and 2D NMR experiments, and the OS was sequenced using a combination of tandem mass spectrometry (MS/MS) data and NMR (CNMR)-C-13 glycosylation shifts. The structure of the native PS was determined using NMR spectroscopy, and it consists of branched pentasaccharide repeating units joined by phosphodiester linkages: -> 4)[alpha-L-QuipNAc-(1 -> 3)]-alpha-D-GalpNAc6Ac-(1 -> 6)-alpha-D-Glcp-(1 -> P-4)-alpha-L-QuipNAc-(1 -> 3)-beta-D-GlcpNAc-(1 ->; the O-acetyl groups represent 0.4 equivalents per repeating unit. Both the OS and PSs exhibit rare conformational behavior since two of the five anomeric proton resonances could only be observed at an elevated temperature.
The structure of the O-antigen polysaccharide (PS) from Escherichia coli O42 has been investigated by NMR spectroscopy as the main method, which was complemented with sugar analysis, mass spectrometry, and analysis of biosynthetic information. The O-specific chain of the O-deacylated lipopolysaccharide (LPS-OH) consists of branched tetrasaccharide-glycerol repeating units joined by phosphodiester linkages. The lipid-free polysaccharide contains 0.8 equiv of O-acetyl groups per repeating unit and has the following teichoic acid-like structure: Based on biosynthetic aspects, this should also be the biological repeating unit. This O-antigen structure is remarkably similar to that of E. coli O28ac, differing only in the presence or absence, respectively, of a glucose residue at the branching point. The structural similarity explains the serological cross-reactivity observed between strains of these two serogroups, and also their almost identical O-antigen gene cluster sequences. -> 2)-(R)-Gro-(1-P-4)-beta-D-GlcpNAc-(1 -> 3)-beta-D-Galf2Ac-(1 -> 3)-alpha-D-GlcpNAc-(1 -> vertical bar a-D-Glcp-(1 -> 3)
A novel protocol for the synthesis of tetrasubstituted olefins through a biomimetic approach has been explored. Both mono- and diarylations were performed under ambient oxygen pressure, giving a range of highly hindered tetrasubstituted alkenes. For diarylation of disubstituted substrates, it was demonstrated that the second arylation is the rate-limiting step of the overall transformation.
An anti-oncological active spiro-oxindole 7 was synthesized regioselectively via a [3+2]-cycloaddition reaction of azomethine ylide to exocyclic olefinic linkage of 4-piperidone 6, exhibiting properties against diverse tumor cell lines including leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney. Compound 7 crystallizes in the monoclinic system and P21/c space group with four molecules in the unit cell. The structure was also studied by AM1, PM3 and DFT techniques. DFT studies support the stereochemical selectivity of the reaction and determine the molecular electrostatic potential and frontier molecular orbitals.
In this thesis, within the topic of bioorganic chemistry, the molecular structure of carbohydrates has been studied. Carbohydrates, or glycans, are ubiquitous biomolecules exhibiting a wide range of biological roles. The specific functions of these molecules are largely determined by their interactions with proteins and molecular structure ultimately governs such specialized recognition events.
Glycan-binding proteins, such as lectins or enzymes, often interact with their sweet ligands in a transient fashion and nuclear magnetic resonance spectroscopy (NMR) is a viable technique to probe these complexes. In particular, ligand-based NMR techniques have been employed, typically in combination with other biophysical as well as biochemical and computational methods. The aim of this work has been to gain new insights about specific biological systems, to develop methods and to devise protocols for their studies.
The first two papers cover NMR-interaction studies of native ligands as well as inhibitor glycans with the enzyme hen egg-white lysozyme and the lectin botulinum neurotoxin type A. Screening experiments were performed to investigate ligand affinities and selectivities. Solution models in combination with X-ray crystal structures were compared in order to evaluate their agreement and the details of interactions.
A method for application in carbohydrate ligand NMR-screening was developed in paper three. The heteronucleus selenium was exploited as a reporter of selenoglycosides binding to lectins. 77Se NMR spectroscopy proved sensitive to binding events and the presented approach should be useful in large screenings of glycomimetic inhibitors. In order to obtain sufficient amounts of glycans for bioorganic studies their production often relies on chemical synthesis. In the last paper, the structure of some conformationally highly activated glycosyl donors was thoroughly investigated and related to their reactivity in synthetic glycosylation reactions.
The iridium-catalyzed C(sp(3))-H borylation of methylchlorosilanes is investigated by means of density functional theory, using the B3LYP and M06 functionals. The calculations establish that the resting state of the catalyst is a seven-coordinate Ir(V) species that has to be converted into an Ir(III)tris(boryl) complex in order to effect the oxidative addition of the C-H bond. This is then followed by a C-B reductive elimination to yield the borylated product, and the catalytic cycle is finally completed by the regeneration of the active catalyst over two facile steps. The two employed functionals give somewhat different conclusions concerning the nature of the rate-determining step, and whether reductive elimination occurs directly or after a prior isomerization of the Ir(V) hydride intermediate complex. The calculations reproduce quite well the experimentally-observed trends in the reactivities of substrates with different substituents. It is demonstrated that the reactivity can be correlated to the Ir-C bond dissociation energies of the corresponding Ir(V) hydride intermediates. The effect of the chlorosilyl group is identified to originate from the alpha-carbanion-stabilizing effect of the silicon, which is further reinforced by the presence of an electron-withdrawing chlorine substituent. Furthermore, the source of selectivity for the borylation of primary over secondary C(sp(3))-H can be explained on a steric basis, by repulsion between the alkyl group and the Ir/ligand moiety. Finally, the difference in the reactivity between C(sp(3))-H and C(sp(2))-H borylation is investigated and rationalized in terms of distortion/interaction analysis.
The copper-catalyzed oxytrifluoromethylation of phenylacetylenes and C-H trifluoromethylation of quinones were studied. It was found that both reactions are accelerated by B(2)pin(2) and PCy3 additives. The two reactions have different substituent effects. The oxytrifluoromethylation is faster in the presence of electron-donating groups, while the C-H trifluoromethylation is faster with electron-withdrawing substituents. The Hammett plot for oxytrifluoromethylation gave a rho value of 0.76 indicating electron demand in the rate determining step of the reaction. According to the absolute value of rho the reaction probably does not proceed through a rate determining formation of a carbocation intermediate. The kinetic isotope effect measurements indicate that in C-H trifluoromethylation of quinones the cleavage of the C-H bond is not the rate determining step of the reaction.
An enantioselective oxidative carbocyclization-borylation of enallenes that is catalyzed by palladium(II) and a Bronsted acid was developed. Biphenol-type chiral phosphoric acids were superior co-catalysts for inducing the enantioselective cyclization. A number of chiral borylated carbocycles were synthesized in high enantiomeric excess.
Comprehensive mechanistic studies on the enantioselective aldol reaction between isatin (1a) and acetone, catalyzed by L-leucinol (3a), unraveled that isatin, apart from being a substrate, also plays an active catalytic role. Conversion of the intermediate oxazolidine 4 into the reactive syn-enamine 6, catalyzed by isatin, was identified as the rate-determining step by both the calculations (G=26.1kcalmol(-1) for the analogous L-alaninol, 3b) and the kinetic isotope effect (k(H)/k(D)=2.7 observed for the reaction using [D-6]acetone). The subsequent reaction of the syn-enamine 6 with isatin produces (S)-2a (calculated G=11.6kcalmol(-1)). The calculations suggest that the overall stereochemistry is controlled by two key events: 1)the isatin-catalyzed formation of the syn-enamine 6, which is thermodynamically favored over its anti-rotamer 7 by 2.3kcalmol(-1); and 2)the high preference of the syn-enamine 6 to produce (S)-2a on reaction with isatin (1a) rather than its enantiomer (G=2.6kcalmol(-1)).
The disaccharide trehalose (TRH) strongly affects the physical properties of lipid bilayers. We investigate interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH using NMR spectroscopy and molecular dynamics (MD) computer simulations. We compare dipolar couplings derived from DMPC/TRH trajectories with those determined (i) experimentally in TRH using conventional high-resolution NMR in a weakly ordered solvent (bicelles), and (ii) by solid-state NMR in multilamellar vesicles (MLV) formed by DMPC. Analysis of the experimental and MD-derived couplings in DMPC indicated that the force field used in the simulations reasonably well describes the experimental results with the exception for the glycerol fragment that exhibits significant deviations. The signs of dipolar couplings, not available from the experiments on highly ordered systems, were determined from the trajectory analysis. The crucial step in the analysis of residual dipolar couplings (RDCs) in TRH determined in a bicelle-environment was access to the conformational distributions derived from the MD trajectory. Furthermore, the conformational behavior of TRH, investigated by J-couplings, in the ordered and isotropic phases is essentially identical, indicating that the general assumptions in the analyses of RDCs are well founded.
This thesis is focused on hydrogen transfer reactions using N-heterocyclic carbenephosphine iridium catalysts and is divided in two parts. The first part describes the use of achiral N-heterocyclic carbene-phosphine iridium complexes catalyzing the methylation of ketones and alkylation of amides using alcohols as the electrophile. In Chapter 2, the N-heterocyclic carbene-phosphine iridium complexes that have been developed in the Andersson group was employed as catalysts for the methylation of ketones. These reactions were found to take place under mild conditions with low catalyst loading (1.0 mol%) to furnish the desired methylated products in up to 98% isolated yield. The achiral N-heterocyclic carbene-phosphine iridium complexes were also found to catalyze the N-alkylation of amides with alcohols, as presented in Chapter 3. It was discovered that the reactivity of the catalysts was highly dependent on the structure of the catalyst. At optimum reaction conditions, the best catalyst could be used with a wide range of substrates at low catalyst loading (0.5 mol%) to afford the desired product up to 98% isolated yield.
The second part of this thesis details the preparation of chiral N-heterocyclic carbenephosphine iridium complexes and their use in the asymmetric hydrogenation of ketones (Chapter 4). These catalysts were successfully used in the asymmetric hydrogenation of ketones at room temperature under base-free conditions and led to full conversion of chiral alcohol products in 30 min with high enantiomeric excess (up to 96%).
N-heterocyclic carbene-phosphine iridium complexes (NHC-Ir) were developed/found to be a highly reactive catalyst for N-monoalkylation of amides with alcohols via hydrogen transfer. The reaction produced the desired product in high isolated yields using a wide range of substrates with low catalyst loading and short reaction times.
In this review the stereochemistry of palladium-catalyzed addition of nucleophiles to alkenes is discussed, and examples of these reactions in organic synthesis are given. Most of the reactions discussed involve oxygen and nitrogen nucleophiles; the Wacker oxidation of ethylene has been reviewed in detail. An anti-hydroxypalladation in the Wacker oxidation has strong support from both experimental and computational studies. From the reviewed material it is clear that anti-addition of oxygen and nitrogen nucleophiles is strongly favored in intermolecular addition to olefin-palladium complexes even if the nucleophile is coordinated to the metal. On the other hand, syn-addition is common in the case of intramolecular oxy- and amidopalladation as a result of the initial coordination of the internal nucleophile to the metal.
A mild and highly efficient catalytic hydrosilylation protocol for room-temperature ester reductions has been developed using diethylzinc as the catalyst. The methodology is operationally simple, displays high functional group tolerance and provides for a facile access to a broad range of different alcohols in excellent yields.
Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for the reduction of tertiary amides under mild reaction conditions employing cost-effective polymeric silane (PMHS) as the hydride source. Crucial for the catalytic activity was the addition of a substoichiometric amount of lithium chloride to the reaction mixture. A series of amides containing different additional functional groups were reduced to their corresponding amines, and the products were isolated in good-to-excellent yields.
Insight into how H2O is oxidized to O-2 is envisioned to facilitate the rational design of artificial water oxidation catalysts, which is a vital component in solar-to-fuel conversion schemes. Herein, we report on the mechanistic features associated with a dinuclear Ru-based water oxidation catalyst. The catalytic action of the designed Ru complex was studied by the combined use of high-resolution mass spectrometry, electrochemistry, and quantum chemical calculations. Based on the obtained results, it is suggested that the designed ligand scaffold in Ru complex 1 has a non-innocent behavior, in which metal-ligand cooperation is an important part during the four-electron oxidation of H2O. This feature is vital for the observed catalytic efficiency and highlights that the preparation of catalysts housing non-innocent molecular frameworks could be a general strategy for accessing efficient catalysts for activation of H2O.
Herein is described the preparation of a dinuclear molecular Ru catalyst for H2O oxidation. The prepared catalyst mediates the photochemical oxidation of H2O with an efficiency comparable to state-of-the-art catalysts.
In a previous detailed study of all the steps of water oxidation in photosystem II, it was surprisingly found that O-2 release is as critical for the rate as O-O bond formation. A new mechanism for O-2 release has now been found, which can be described as an opening followed by a closing of the interior of the oxygen evolving complex. A transition state for peroxide rotation forming a superoxide radical, missed in the previous study, and a structural change around the outside manganese are two key steps in the new mechanism. However, O-2 release may still remain rate-limiting. Additionally, for the step forming the O-O bond, an alternative, experimentally suggested, mechanism was investigated. The new model calculations can rule out the precise use of that mechanism. However, a variant with a rotation of the ligands around the outer manganese by about 301 will give a low barrier, competitive with the old DFT mechanism. Both these mechanisms use an oxyl-oxo mechanism for O-O bond formation involving the same two manganese atoms and the central oxo group (O5).
For the main parts of the mechanism for water oxidation in photosystem II there has recently been very strong experimental support for the mechanism suggested by theoretical model studies. The question addressed in the present study is to what extent this knowledge can be used for the design of artificial catalysts. A major requirement for a useful artificial catalyst is that it is small enough to be synthesized. Small catalysts also have the big advantage that they could improve the catalysis per surface area. To make the mechanism found for PSII useful in this context, it needs to be analyzed in detail. A small model system was therefore used and the ligands were replaced one by one by water-derived ligands. Only the main chemical step of O-O bond formation was investigated in this initial study. The energetics for this small model and the larger one previously used for PSII are remarkably similar, which is the most important result of the present study. This shows that small model complexes have a potential for being very good water oxidation catalysts. It was furthermore found that there is a clear correlation between the barrier height for O-O bond formation and the type of optimal structure for the S-3 state. The analysis shows that a flexible central part of the complex is the key for efficient water oxidation.
Most of the main features of water oxidation in photosystem II are now well understood, including the mechanism for O-O bond formation. For the intermediate S-2 and S-3 structures there is also nearly complete agreement between quantum chemical modeling and experiments. Given the present high degree of consensus for these structures, it is of high interest to go back to previous suggestions concerning what happens in the S-2-S-3 transition. Analyses of extended X-ray adsorption fine structure (EXAFS) experiments have indicated relatively large structural changes in this transition, with changes of distances sometimes larger than 0.3 angstrom and a change of topology. In contrast, our previous density functional theory (DFT)(B3LYP) calculations on a cluster model showed very small changes, less than 0.1 angstrom. It is here found that the DFT structures are also consistent with the EXAFS spectra for the S2 and S3 states within normal errors of DFT. The analysis suggests that there are severe problems in interpreting EXAFS spectra for these complicated systems.
The quantum chemical cluster approach was used to elucidate the reaction mechanism of debromination catalyzed by the B12-dependent reductive dehalogenase NpRdliA. Various pathways, involving different oxidation states of the cobalt ion and different protonation states of the model, have been analyzed in order to find the most favorable one. We find that the reductive C Br cleavage takes place exclusively at the Co' state via a heterolytic pathway in the singlet state. Importantly, the C-H bond formation and the C Br bond cleavage proceeds via a concerted transition state, as opposed to the stepwise pathway suggested before. C Br cleavage at the Coll state has a very high barrier, and the reduction of Co' to Co is associated with a very negative potential; thus, reductive dehalogenation at Coll and Co can be safely ruled out. Examination of substrate with different halogen substitutions (F, Cl, Br, I) shows that the dehalogenation reactivity follows the order C I > C Br > C-C1 > C-F, and the barrier for defluorination is so high that NpRdhA cannot catalyze that reaction.
The synthesis of Mn-based catalysts to mimic the structural and catalytic properties of the oxygen-evolving complex in photosystem II is a long-standing goal for researchers. An interesting result in this field came with the synthesis of a Mn complex that enables water oxidation driven by the mild single-electron oxidant [Ru(bpy)(3)](3+). On the basis of hybrid density functional calculations, we herein propose a water oxidation mechanism for this bioinspired Mn catalyst, where the crucial O-O bond formation proceeds from the formal Mn-4(IV,IV,IV,V) state by direct coupling of a Mn-IV-bound terminal oxyl radical and a di-Mn bridging oxo group, a mechanism quite similar to the presently leading suggestion for the natural system. Of importance here is that the designed ligand is shown to be redox-active and can therefore store redox equivalents during the catalytic transitions, thereby alleviating the redox processes at the Mn centers.
Benzoyl-CoA epoxidase is a dinuclear iron enzyme that catalyzes the epoxidation reaction of the aromatic ring of benzoyl-CoA with chemo-, regio- and stereo-selectivity. It has been suggested that this enzyme may also catalyze the deoxygenation reaction of epoxide, suggesting a unique bifunctionality among the diiron enzymes. We report a density functional theory study of this enzyme aimed at elucidating its mechanism and the various selectivities. The epoxidation is suggested to start with the binding of the O-2 molecule to the diferrous center to generate a diferric peroxide complex, followed by concerted O-O bond cleavage and epoxide formation. Two different pathways have been located, leading to (2S,3R)-epoxy and (2R,3S)-epoxy products, with barriers of 17.6 and 20.4 kcal mol(-1), respectively. The barrier difference is 2.8 kcal mol(-1), corresponding to a diastereomeric excess of about 99 : 1. Further isomerization from epoxide to phenol is found to have quite a high barrier, which cannot compete with the product release step. After product release into solution, fast epoxide-oxepin isomerization and racemization can take place easily, leading to a racemic mixture of (2S,3R) and (2R,3S) products. The deoxygenation of epoxide to regenerate benzoyl-CoA by a diferrous form of the enzyme proceeds via a stepwise mechanism. The C2-O bond cleavage happens first, coupled with one electron transfer from one iron center to the substrate, to form a radical intermediate, which is followed by the second C3-O bond cleavage. The first step is rate-limiting with a barrier of only 10.8 kcal mol(-1). Further experimental studies are encouraged to verify our results.
Density functional theory calculations have been used to study the reaction mechanism of water oxidation catalyzed by a tetranuclear Mn-oxo cluster Mn4O4L6 (L = (C6H4)(2)PO4-). It is proposed that the O-O bond formation mechanism is different in the gas phase and in a water solution. In the gas phase, upon phosphate ligand dissociation triggered by light absorption, the O-O bond formation starting with both the Mn-4(III,III,IV,IV) and Mn-4(III,IV,IV,IV) oxidation states has to take place via direct coupling of two bridging oxo groups. The calculated barriers are 42.3 and 37.1 kcal/mol, respectively, and there is an endergonicity of more than 10 kcal/mol. Additional photons are needed to overcome these large barriers. In water solution, water binding to the two vacant sites of the Mn ions, again after phosphate dissociation triggered by light absorption, is thermodynamically and kinetically very favorable. The catalytic cycle is suggested to start from the Mn-4(III,III,III,IV) oxidation state. The removal of three electrons and three protons leads to the formation of a Mn-4(III,IV,IV,IV)-oxyl radical complex. The O-O bond formation then proceeds via a nucleophilic attack of water on the Mn-IV-oxyl radical assisted by a Mn-bound hydroxide that abstracts a proton during the attack. This step was calculated to be rate-limiting with a total barrier of 29.2 kcal/mol. This is followed by proton-coupled electron transfer, O-2 release, and water binding to start the next catalytic cycle.
PhoX is a pentanudear metalloenzyme that employs two ferric ions and three calcium ions to catalyze the hydrolysis of phosphomonoesters. On the basis of the X-ray structure of PhoX (Science 2014, 34S, 1170-1173), a model of the active site is designed, and quantum chemical calculations are used to investigate the reaction mechanism of this enzyme. The calculations support the experimental suggestion, in which the two high spin ferric ions interact in an antiferromagnetic fashion. The two step mechanism proposed by experimentalists has been investigated. The nudeophilic attack of a trinudear bridging oxo group on the phosphorus center was calculated to be the first step, which is concomitant with the departure of the phenolate, which is stabilized by a calcium ion. The second step is a reverse attack by a water molecule activated by a calciumbound hydroxide, leading to the regeneration of the bridging oxo group. The second step was calculated to have a barrier of 27.6 kcal/mol. The high barrier suggests that the alternative mechanism involving phosphate release directly from the active site seems to be more likely. All five metal ions are involved in the catalysis by stabilizing the pentacoordinated trigonal bipyramidal transition states.


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Bill Murray is a wonderful storyteller. A couple of years ago, I linked to this wonderful interview with Bill Murray by Howard Stern. In this radio interview, Murray said the key to being funny was being able to tell stories. How, then, does one become a good storyteller, Stern asked. "Is it something you are born with?" Murray's reply:
"No, I don't think you're born with it. You have to hear stories and you have to live stories. You have to have a bunch of experiences and be able to say 'Here's something that happened to me yesterday....' And if you can make people laugh by telling them what happened to you, then you are telling the story well. So that's what I learned in improv...."
People often ask great storytellers—writers, producers, directors, authors, etc.—where they come up with their stories. They inevitably say something like "write/tell what you know." In other words, write (or speak) from your own life experiences. This is why I always say you have to live a life to tell a life. I believe this is what Murray is saying above when he says it's important to have a "bunch of experiences" from which to draw. The experiences—good and bad (but especially bad)—are like a persona library of history and insights for the storyteller.
The video above is a nice example of a simple, short story that Murray tells, seemingly impromptu, to a question from the press during a panel interview for the film The Monuments Men. Most people may think nothing of this tale from his life, but it's a great example of the everyday kind of real-life memory from one's past which holds a lesson or a gem of wisdom. His recollection is a kind of "man-in-hole" story. Right from the beginning, we hear of a traumatic failing that sends Murray out onto the streets of Chicago for a long walk. He's at his lowest, and things look like they will get worse. He continues to walk, not feeling especially hopeful, until he stumbles upon the Art Institute of Chicago. There, expecting nothing, he is moved by a piece of art. His day went from one of his worst to one with hope and a new perspective, in part because of being exposed to The Song of The Lark, an 1884 painting by Jules Adolphe Breton.
In cooperation with the Khan Academy, Pixar and Disney have been offering Pixar in a Box, an on-going series of behind-the-scenes lessons taught by Pixar's professionals (storytellers, animators, directors, artists, etc.). Subjects have included color science, animation, effects, sets & staging, character modeling, and so on. Part of the aim of this project, as stated on the Pixar-in-a-Box website is to show how "The subjects you learn in school — math, science, computer science, and humanities — are used every day to create amazing movies at Pixar."
These lessons are remarkable, but what I am most excited about is that last week, Pixar in a Box announced a new series: The Art of Storytelling. Pixar may be the best at the technical side of animation, but what really made them successful is their understanding of story and storytelling. In this interview regarding Pixar's success, Steve Jobs said this: "Even though Pixar is the most technologically advanced studio in the world, John Lasseter has a saying which has really stuck: No amount of technology will turn a bad story into a good story."
The new Art of Storytelling series is great news for educators who want to bring the principles of storytelling into the classroom and help their students understand the art of story. Yet this is also useful for anyone who wants to become a masterful storyteller in business or in any other endeavor. Here's the introduction video for the Storytelling series.
The storytelling series will cover six main parts that take you from the formation of your rough idea to actually creating storyboards. Each lesson features videos and activities, so this is something you can do on your own or as part of a class. Here are the six sections to be covered as outlined in the introductory video in lesson 1:
(1) We are all Storytellers
(2) Character
(3) Structure
(4) Visual language
(5) Filmmaking grammar
(6) Storyboarding
Currently, all six lessons are available. Even if you do not desire to make an animated film, the lessons — especially those related to structure and visual language — will help you create better presentations in all their myriad forms or incorporate storytelling into other aspects of your work and life.
If you have not heard of Pixar in a Box, here is a video presentation that explains the concept. And in the true spirit of Pixar, the video introduction is done with great clarity and humor.
Related Links
• The Art of Storytelling (Khan Academy)
• Tips for creative success from Pixar
• No amount of technology will make a bad story good
• Study the basics: John Lasseter on the secret to success
• Pixar's 22 Rules of Storytelling
• The storytelling imperative: Make them care!
• 10 tips for improving your presentations & speeches
Here are two good books on Pixar I read recently. The first one is Creativity, Inc.: Overcoming the Unseen Forces That Stand in the Way of True Inspiration. The other book — To Pixar and Beyond: My Unlikely Journey with Steve Jobs to Make Entertainment History — came out at the end of last year. Both give great insights into the workings of Pixar and also the story making process.
The Zen Master of data visualization has died. I am sorry to have to report that Dr. Hans Rosling passed away today in Uppsala, Sweden. He was just 68. A profoundly mournful day for anyone who knew Professor Rosling, obviously. But it's also a sad day for all of us in the greater TED community or data visualization/business intelligence communities as well. Dr. Rosling's work was seen by millions and will continue to be seen by millions worldwide. It is incalculable just how many professionals Hans inspired over the years. His presentations, always delivered with honesty, integrity, and clarity, were aided by clear visuals of both the digital and analog variety. He was a master statistician, physician, and academic, but also a superb presenter and storyteller.
Almost eleven years ago, just after TED began experimenting with putting some of their talks on the web, I wrote this post called "If your idea is worth spreading, then presentation matters." In that post, I summarized my impression of Dr. Rosling from his 2006 TED Talk:
"Hans Rosling, an expert in public health from Sweden, does an amazing job in this presentation bringing the data to life. If you want to know how he did all those graphics, go to gapminder.org. It's all there. Hans is saying the problem is not the data. The data is there. But it's not accessible to most people for three reasons: (1) For researchers and journalists, teachers, etc. it is too expensive. (2) For the media, it is too difficult to access. (3) For the public, students, and policy makers, it is presented in a boring way. His solution is to make the data free, let it evoke and provoke an 'aha' experience, or a 'wow!' experience for the public. I loved the way he got involved with the data, virtually throwing himself into the screen. He got his point across, no question about it."
From that point on, I watched virtually every talk he made and featured him in every book I wrote on presentation. I saw the professor in person at TED 2009 and was a fellow presenter with him at Tableau 2014 in Seattle where he, as usual, had the crowd of data geeks in the palm of his hand. If there is a Zen Master —or Jedi Master — of data visualization, then Dr. Hans Rosling is that master. His contributions are immense, and he will be missed deeply.
Below is Dr. Rosling's debut at TED 2006. It's as good now as it was then.
Hans Rosling presented at TED ten times, more than any other presenter. All of his TED presentations are featured here on the TED website. Below are links to a selection of other posts from presentationzen.com which feature videos and analysis of Dr. Rosling's presentations over the years.
• If your idea is worth spreading, then presentation matters
• Hans Rosling: Don't just show the notes, play the music!
• Hans Rosling: The Jedi Master of Data Visualization
• Hans Rosling redux: Mixing analog with digital visualization
• Hans Rosling: the Zen Master of Presenting Data
• Hans Rosling & the Art of Storytelling with Statistics
His message and spirit live on
Hans Rosling's contribution to the world in his 68 years was extraordinary. I'll continue to do whatever I can to spread his teachings in future. His work will continue to inspire and educate. We need his message of a fact-based worldview now more than ever. Here is part of today's announcement by Anna R. Rönnlund & Ola Rosling which appeared on the Gapminder website:
Across the world, millions of people use our tools and share our vision of a fact-based worldview that everyone can understand. We know that many will be saddened by this message. Hans is no longer alive, but he will always be with us and his dream of a fact-based worldview, we will never let die!
Indeed. Let us all remember Professor's Rosling's contributions and continue to keep the dream of a more fact-based, rational worldview alive.
• Gapminder.org
Edward Tufte is a leading expert in the data analysis and data visualization space. His books are classics and required reading for anyone interested in understanding how best to display quantitative information. I read his books just after I left Apple in 2003 to become a college professor in Japan. His books are foundational. I've talked about Tufte in my own books and on this website going back to at least this post in 2005. I have not seen him speak recently, so I was happy to see this 50-minute presentation by Dr. Tufte which took place at the Microsoft Machine Learning & Data Science Summit 2016 held this past September. Microsoft's David Smith introduced Dr. Tufte at the 2:30 mark.
Video and transcript also available on the Microsoft website.
In his talk, Tufte warns against confirmation bias and massaging the data to arrive at findings that are desirable or somehow in your interest. He paraphrases one of Daniel Patrick Moynihan's famous lines: "Everyone is entitled to their own opinions, but they are not entitled to their own facts." This reminded me of the old Darrell Huff chestnut from How to Lie With Statistics (1954): "If you torture the data long enough, it will confess to anything."
You want to generate your findings from the data not from the analysis, Tufte says. To do this he recommends specifying your analysis first before you collect the data. "This is to avoid all the generating findings just by analysis, not out of the data." Tufte stressed the importance of "...full pre-specification of the analysis so they can't over search the data, so they can't run a million models and publish one. I think this is the future of confirmatory data analysis."
Exploratory and replication
"We should be mucking around in our data to find out what's going on. We can learn from it. We can run it through powerful exploratory things. We can run it like a map through millennial time and look it over and say, that look interesting....and what this means, though, this kind of searching, is that you must have an honest replication of the results of the search. To go back on innocent data, maybe somebody 500 miles away does it. Maybe that's better, independent replication of the search results to distinguish now between noise and signal."
"It is impossible for any normal human being to stare at a spreadsheet and look for contradictions, and problems." This is where data forensics comes in. Tufte recommends the Quartz Guide to Bad Data at GitHub.
Scattering the eye and mind, producing vague anxiety & clutter
At the end of his talk, Tufte said something very wise. Something simple as can be, but it was one of the most important things he said in his talk. After talking about the need for us to learn about the entire process of data and analysis and to go out in the field and watch directly how original measurements are made, Tufte said this:
"In doing creative work do not start your day with addictive time-vampires such as The New York Times, email, and Twitter. All scatter the eye, and mind, produce diverting vague anxiety, clutter short-term memory. Instead, begin with your work. Many creative workers have independently discovered this principle." I completely agree with this.
And finally this bit of wisdom concerning data analysis and thinking in general. The most powerful question you can ask yourself, and of others is: "How do I know that? How do you know that? How do they know that?"
These books by Dr. Tufte —especially The Visual Display of Quantitative Information, Visual Explanations, and Envisioning Information — are ones you want on your bookshelf. They are beautifully designed and well made. Over the years I have come back to these books often. Of course, the examples are dated, but the principles are the same and the examples hold up well and you can easily apply the concepts to modern problems. And they are just beautiful, smart books.
There is loads of evidence that reading to children at bedtime is not only good for their emotional well being, it also has long-term benefits for their cognitive development. We have a 6-year-old girl and a 4-year-old boy. Since they were babies they have been exposed to books. Bedtime stories are one of the great joys of parenting and is a nightly ritual for us. As it is the Christmas season, I thought I would recommend two books here that do a great job of presenting their material in an engaging, visual way.
The first is the classic The Night Before Christmas by Clement Clarke Moore. There are many editions of this classic tale, but based on the amazing and numerous reviews on Amazon, I purchased Robert Sabuda's The Night Before Christmas Pop-up last year in time for Christmas.The pop-up art is amazing and imaginative. I was not sure at first that I would want a pop-up book for story time, but the great thing about the 3-D aspect of it is that the kids are always touching the paper and playing with the tabs and strings as the story progresses. They use their imagination to believe now that the story is about them and their house. In the final two-page spread, for example, a snow-covered town pops up with Santa flying over the houses. My son will say something like "here is our house and this is our bed room window." My daughter would then comment "here's grandma's house and here's our school across the bridge." I read each page, but we spend more time on questions and adding to the narrative before I move on to the next spread. It's a well-made book, but you need to be a bit careful with it, especially with infants. Still, if you are just a little careful, the pop-ups should keep working long after the kids are grown.
My 4-year-old son pulls tab to have Santa and his reindeer fly above the snow covered village.
My 6-year-old daughter opens the page which reveals the eight reindeer and Santa scurrying down the chimney.
The second recommendation is not a pop-up, but rather a series of visual books that come with an audio reader than the child can control. My wife had a business trip to New York City about a year ago and brought back The Disney Star Wars Me Reader. It was an instant hit.The box comes with eight short illustrated books and a durable plastic electronic reader. Of course, I can read the book as my children follow along, but they actually prefer that I hold the book for them as they press the buttons on the reader to go through the story page by page. The electronic reader is intuitive to figure out for the child. We got this Star Wars set over a year ago when my son was 3-years old and he knew how to navigate the analog menus after 1-2 minutes of playing around. The narrator's English is extremely clear and easy to understand and I believe this has helped with their English pronunciation. The kids don't just listen but repeat phrases from the book — "It's a trap!" As we live in Japan, I am about the only person they interact with in English, so tools like this were surprisingly useful. My son is the Star Wars nerd (as am I), so I think we'll get a different Me Reader for my daughter for Christmas such as the Frozen Me Reader.
The Star Wars Radio Youtube channel has a preview of one of the books along with the audio for each book. This should give you a feel for what they are like. We've already gotten a lot of mileage of these books.
May The Force Be With You.
There's a new book just out that focuses on improving the kind of presentations that scholars, researchers, and other technical specialists need to give. The book is Better Presentations: A Guide for Scholars, Researchers, and Wonks by data-visualization pro Jonathan Schwabish. Jonathan is a Senior Research Associate in The Urban Institute's Income and Benefits Policy Center and a member of the institute's communication team where he specializes in data visualization and presentation design. Jonathan is an economist by training and an expert in data visualization. He's a numbers guy with a special skill for helping others communicate their data in ways that engage and connect with an audience.
Jonathan also created the PolicyViz website which features a popular podcast that covers a range of topics related to effective communication and the display of data visualizations. Recently, I was a guest on the PolicyViz podcast. You can hear that episode here on the PolicyViz website.
"Presenting is fundamentally different from writing," says Jonathan. "[But] with only a little more time, a little more effort, and a little more planning, you can communicate your work with force and clarity." Better Presentations is a simple, well-written, visual book that is useful for students, teachers, and other academics, as well as for anyone who needs to give data-driven presentations. Check it out.
• Follow Jonathan here onTwitter.
• The PolicyViz website
• Jonathan's book Better Presentations on Amazon.com
• A great book on using charts called Good Charts by Scott Berinato
• Another book for tech presenters: Presenting for Geeks by Dirk Haun
When Toy Story opened in the US at the end of 1995, it was met with enthusiasm and great critical acclaim. The film would go on to be the highest-grossing film of the year. There was tremendous buzz (ahem) about the film before it arrived here in Japan a few months later. Much of the talk focused on the stunning 3-D animation and the remarkable technical achievements by Pixar to pull this movie off. I remember sitting in a movie theatre in the spring of 1996 in Osaka, Japan watching the film. I was a bit of a technology geek in those days so what propelled me to actually go see the film initially was the fact that it was the first truly digital animation feature film. And yet the thing that impressed me about the movie was that I soon forgot all about how the animation was created and just remembered being engaged by the story. I wanted to see the film again (and again). I thought it was perfect. Fast forward to today and I have seen every Pixar film ever made dozens of times. I have two small children who adore all the Pixar films and I don't mind watching along with them. If there was a degree given out for watching Pixar films, then I'd by working on my PhD by now.
I watch the films repeatedly because my kids ask to see them, and since our DVDs are in English the movies are more than mere entertainment. But truth be told, I love watching the Pixar films because I have learned so much about story structure, story elements, character, etc. simply by seeing them so many times and paying close attention. These films are designed for adults and kids to enjoy and you may not think there is much to learn from these animated features, but you'd be wrong. Lasseter has said that the first 18 months of working on Toy Story was spent laboring just on the script, that is, the story. The animation is awesome, but it's the story that hooks you, holds you, and rewards you at the end. And it is really, really hard to craft a good one.
There are many lessons from Pixar's prowess at storytelling that we can take and apply to other forms of storytelling, including the 21st-century short-form presentation format. At the end of this documentary on the making of Toy Story, filmed before the film was released, there is a great line by Pixar's now legendary John Lasseter:
"Everyone's going to talk about the fact that this is the very first computer animated feature film, but the computers are just tools [the computers] didn't create this picture, it's the people who created the picture." — John Lasseter
In spite of Pixar's amazing technology, there has always been a focus on the people creating the picture, the people in the audience, and above all, the commitment to the story and the story process.
Steve Jobs on Pixar, Hollywood, and Story
In this 2007 interview of Steve talking with Wall Street Journal columnists Kara Swisher and Walt Mossberg, Jobs tells how the typical live action film will shoot between 10- to one 100-times more footage than will actually appear in the film. After shooting, the film is assembled in editing, which leaves most of what was shot on the cutting room floor. But animation is much too expensive to create a film in this way. Because animation is so expensive you have to edit the film before you actually make it, Jobs explains. This is where storyboarding comes in. The story team has sketches of each scene which follow the progression of the script. A film could have thousands of these.
A good book I often recommend is: Yes!: 50 Scientifically Proven Ways to Be Persuasive by Dr. Robert B. Cialdini et al. I first read the book when it came out in 2008. The book is designed for professionals who are interested in becoming better at understanding how to persuade or influence others. The book may also help you understand why you decide to do the things you do. Even if you are a researcher or teacher or a medical doctor, and so on, and not a business person, it's still important to understand how people are (or can be) influenced and persuaded by your words and behaviors. Each chapter focuses on a single question and is no more than 3-5 pages long. If you want to go deeper you can checkout the sources for each chapter in the Notes section.
"Yes!" is not a textbook, and it may not go deep enough for some, but for extremely busy professionals, this is a useful book with many clear, quick lessons that will get you thinking.
Above: The book on my desk. Each chapter focuses on a question such as what common mistake causes messages to self-destruct, how sticky notes can make your messages stick, etc. Checkout the table of contents here to see all 50 chapters at a glance.
If you want a little more depth, I suggest Cialdini's other huge bestsellers Influence: The Psychology of Persuasion and Influence: Science and Practice. These books have sold in the millions by now. Some people may be skeptical about the ethics of trying to persuade and influence others, but remember, it's not just about marketers trying to influence someone to buy something they do not need with money they do not have. Persuasion can be used for good just as it can be used for ignoble reasons. For example, a medical doctor often needs to be effective at persuading patients to comply with her recommendations. Facts, data, and argument are usually not enough to influence a change in behavior.
If you do not have enough time to read the Influence books yet, the 12-minute video below will give you a good idea as to the key findings in Cialdini's research. The video presentation covers the six universal principles of persuasion which are scientifically proven, according to the author, to make you more effective at influence and persuasion. (Watch below or on YouTube.)
Principles of Persuasion at a glance
In an ideal world people would use reliable information and sound logic to guide their thinking and decision making, but the reality is people use shortcuts or "rules of thumb" to make decisions. The six shortcuts below, according to the author, are universal rules of thumbs that guide human behavior. The key is to understand these shortcuts and use them in an ethical manner to persuade others. There are many examples in the books, but in the video they can only give one or two. Here are the six principles in brief.
(1) Reciprocity. The obligation to give back when you have previously received. The key takeaway: Be the first to give and make it personal and unexpected.
(2) Scarcity. People want more of those things which are perceived to be rare or in short supply. It's not enough to tell people about the benefits they will gain, you must also tell them what they stand to lose or miss out on if they do not adopt your idea (or buy your product, or choose your school, etc.).
(3) Authority. People will follow the lead of credible, knowledgeable experts. In the presentation space, it's highly desirable to have someone give a short and concise introduction of yourself which highlights why you are an expert worth listening to.
(4) Consistency. Asking for small commitments that can easily be made. Then going back and asking for larger commitments later. Sometimes this is called "getting a lot by first asking for a little." People want to be consistent, according to the principle, so if they said yes to you previously they are more likely to do it again.
(5) Liking. People prefer to say yes to the people they like. There are three factors in determining whether we like someone (a presenter on stage, for example). We tend to like people (1) who are similar to us, (2) who pay us compliments, and (3) who cooperate with us. For presenters it's important to really know your audience so that you can touch immediately on something shared and personal with the audience.
(6) Consensus. People often look to the actions of others to determine their own. So rather than simply hitting people over the head with your logic and data trying to persuade them to accept your idea, you can also elaborate on all the other people who have already accepted your proposal.
• www.influenceatwork.com

subset: commoncrawl


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Adri from Dream Book Design picked up a gorgeous tablecloth from Anthropologie, and it had a beautiful navy floral mandala design. Adri, however, was really hoping for a beautiful navy blue rug akin to Pier 1 and other designer rugs. Since Adri had already purchased the tablecloth, she opted to DIY her own beautiful rug. Adri coated the tablecloth … [Read more...]
Easy Wallpaper Coasters
Lauren from The Thinking Closet was desperately searching for coasters to dispel the drink rings she was collecting on her furniture. Rather than shelling out the cash for expensive colorful coasters from Pier 1 or Anthropologie, she opted to DIY her own. Lauren collected wallpaper samples from Anthropologie and Farrow & Ball to create a … [Read more...]
DIY Decorative Mirror from a Dinner Plate
Meghan from Blitsy Blog was getting rid of her old set of plain white dishes when she realized that she could use them to DIY her own unique wall mirror. Round mirrors are used in gallery walls and other decor to add shape and texture to a room. Using a few different colors of paint pens, Meghan created a unique piece of decor that only cost her a … [Read more...]
DIY Gold Bird Art
This morning I shared a DIY pinboard created by Shauna at Satori Design for Living. If you loved that touch of gold she added to her frame, here's another gilding project from Shauna that brings on the glitz. Shauna was inspired by a tray featuring a silver leafed bird motif to create framed art with a similar look. All she did was print an image … [Read more...]
Burlap Magnolia Blooms for Fall
With the arrival of each new season, Gail from Purple Hues and Me says she loves to visit Pier 1 for inspiration. On a recent trip she saw some pretty handcrafted branches of burlap magnolia stems and was inspired to recreate these lovelies. Gail hit up her fabric stash for leftover burlap and formed it into realistic looking blooms with the help … [Read more...]
Stool Upholstered with Rug
Kim from Made in a Day scored quite the deal when she got an old stool for only $1.99. It might not have been much to look at, but Kim took care of that! She recovered the seat with a kitchen rug from Wal-mart to mimic the look of hand-woven, recycled fabric stools she had seen at both Pier 1 and Target. I love it when a rescue and knock-off come … [Read more...]
Ornament Wreath
Rather than spending $40-60 on an ornament wreath at a store, Virginia of LiveLoveDIY spent $7 making her own from dollar store items. This glitzy beauty ranks as one of Virginia's favorite projects this year. If you're thinking you've run out time for wreath-making, think again! Virginia whipped up her wreath in just an hour! Virginia was … [Read more...]
Lamp with Lace Shade
When Denisa from A Girl and A Brush saw a lace lamp at Pier 1, she knew it was perfect for her bedroom. That is… the lamp was perfect, not the $75 price tag. Using a Goodwill lamp base, shade, and tank top, Denisa created her own romantic lamp for less than $15! Denisa was inspired by the Vintage Lace Lamp from Pier 1 Imports. Head on over … [Read more...]
Distressed Wall Clock
Carrie at Dittle Dattle was inspired to create her own ginormous wall clock after spying one on a date night with hubby. The laminate top from a table that had been in the attic for years was the perfect "canvas" for the clock face. Carrie is so awesome that she cut all the numbers with her scroll saw just to get the right size. She even added her … [Read more...]
Decorative Photo Lantern
Brittany at Pretty Handy Girl snatched up an old brass lantern from her Habitat Restore for only $5. She turned it into a decorative piece for her mantle with some colorful paint and a picture of two cutie pies. Brittany didn't even realize her pretty blue lantern resembled candle lanterns from Pier 1. She's just that awesome all by herself! … [Read more...]


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Point Localization: 1 fen above and medial to the medial angle of the eye.
TCM Actions: Expels Wind. Clears Heat. Enlightens the eyes. Controls the rise of the Yin Qi and Yang Qi to the eyes.
Indications: Any ocular dysfunction. Conjunctivitis. Lacrimation. Dry eyes. Headache. Redness, swelling, pain and itching in the eyes. Vision problems. Insomnia (along with Ki6 + Bl62). Sleepiness (along with Ki6 and Bl62).
Target area: Eyes.
Point Name and Meaning: Jingming – Bright Eyes
Acupuncture Meridian: Bladder
Categories: None.
Unitary Channel: Tai Yang (Greater Yang) [SI + BL]
*Acupuncture points may be used safely for acupressure, but should be used with needles only by acupuncturists or Traditional Chinese Medicine (TCM) professionals.


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Click the follwing links to get APGLI full information
The acronym of APGLI is Andhra Pradesh Government Life Insurance Fund. which is a Scheme of Social Security Measure for welfare of the Government Employees and is very important for all Government and provincialised Local Body Employees. APGLI Department is under the Administrative Control of Finance Department,to find your Amount totals quote correct policy numbers in the Schedule to avoid missing credits. APGLI policies do not lapse and premium rates are low. The official site of APGLI is www.apgli.ap.gov.in
APGLI premium is exempted from income tax under Section 80C. AP State Government Employee's can contribute maximum premium upto 20% of the basic pay, irrespective of slab rates.
All the Policy Holders are hereby requested to submit the following information while submitting applications
for sanction of Loan/Settlement of Claim cases for making payment online & sending SMS.
Government has revised APGLI Slab Rates as per New Salaries in RPS 2010.
The APGLI Department is one of the oldest departments in the State. The Scheme was originally started in 1907 by the Nizam of erstwhile State of Hyderabad for the welfare of his employees.
A Management Committee used to run the scheme initially in the name of Family Pension Fund. Later the scheme was renamed as Hyderabad State Life Insurance Fund in the year 1913.
After formation of Andhra Pradesh state in 1956, the scheme was changed as "Andhra Pradesh Government Life Insurance Fund". The first Managing Committee meeting after formation of Andhra Pradesh State consisting of 4 members, one Secretary and a President was held on 25-9-1957 and Sri B.Gopala Reddi, the then Honorable Finance Minister was President of the meeting.
APGLI Scheme is a Social Security Measure for the welfare of the Government employees and is mandatory for all Government employees and provincialised Local Body employees.
APGLI Department is under the Administrative Control of Finance Department.
1. Till 1976, there was only one office at Hyderabad.
2. During 1976, the department was reorganized by opening four Regional Offices, one each at Hyderabad, Warangal, Vijayawada and Kurnool. The following were the Regional Offices' jurisdiction:
Districts under Hyderabad Regional Office:
Hyderabad ,
Ranga Reddy,
Medak ,
Nizamabad ,
Districts under Warangal Regional Office
Warangal ,
Khammam ,
Karimnagar ,
Districts under Vijayawada Regional Office
Srikakulam ,
Vizianagaram ,
Visakhapatnam ,
East Godavari ,
West Godavari ,
Districts under Kurnool Regional Office
Prakasam ,
Nellore (now Sri Potti Sriramulu Nellore District) ,
Kurnool ,
Kadapa ,
Anantapur ,
Chittoor .
The viewers are requested, if any link provided here is found false please feel free to mail to rectify the error and make use of all teachers and Studens of Andhra Pradesh . Our contact information and mail is firstname.lastname@example.com .
Facebook See my profile at


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Tag: pond
Plover Way, SE16written by neja on 2011-04-14 #places
Swan Lake of South East London3 9 Share Tweet
Balboa Park San Diego, CAwritten by jblaze823 on 2010-02-24 #places
Balboa Park is a massive park in San Diego, CA that includes museums, the world famous San Diego Zoo, and many other photographic eye-catchers.6 5 Share Tweet
Palace of Fine Arts - San Francisco, CAwritten by jblaze823 on 2009-07-16 #places
The Palace of Fine Arts is an architectural beauty, and one of the many locations that make San Francisco such a wonderful city.8 4 Share Tweet
Falling In Love With The Diana F+ (Again)written by ashleyaang on 2012-09-12
I'll be honest - I never had much luck with the Diana F+. I loved it the first time I used it, then it went downhill from there. I've been picking it back up recently, and well, I think I'm in love again!1 8 Share Tweet
Ensign Bellows Camerawritten by dogtanian on 2010-10-17 #gear
I don't really know much about this camera, I tried doing a bit of research about it but came up with not a lot about this camera and a whole lot about other ensign cameras, it was made by the ensign company which started production of cameras in 1905 after many years of producing optical glass etc. as far as i can gather/guess this camera started production in the late 1920's.2 6 Share Tweet
Wimbledon Common - No Wombles in Sightwritten by simonh82 on 2011-03-23 #places
Fictional litter picking rodents may be the thing which Wimbledon Common is best known for, but so far I've never seen a womble. What you definitely find is a beautiful piece of common land, with woods, lakes, fantastic walks, and horse riding toffs.3 3 Share Tweet
Maymont Parkwritten by plaidleaf on 2009-09-20 #places
Wandering about and taking in the scenery is one of my favorite pastimes; I'm betting it's one of yours too. You can take in scenery just about anywhere, but Maymont is pretty special. It's 100 acres of pure green beauty interspersed with various gardens and animal sanctuaries. In my eyes, it's like a miniature version of New York's Central Park (minus the ice skating rink) in the middle of Richmond.3 3 Share Tweet
Riparian Preserve at Water Ranch Gilbert, Arizona.written by blue-dog on 2010-08-15 #places
On a recent vacation (which was not my first choice of vacation destinations), I chanced upon the Riparian Preserve at Water Ranch Gilbert, Arizona, which is a beautiful sanctuary in the middle of the city. It certainly blew me away!2 3 Share Tweet
Hampstead Heath, Londonwritten by neja on 2008-11-29 #places
London might be a megapolis with the population over 12 millions of people, but it is also one of the greenest cities you can ever find. It is full of parks, marshes, woods and so on. Hampstead Heath is one of the London's biggest treasures. It is a massive park on the hills, with ponds for nudists, people in bikinis and all sorts of ducks and swans. It is favorite destination for parents with children, kite flyers and dog walkers, not to count the tourists and fans of the spectacular views.2 3 Share Tweet
My Favorite Patch of Greenery: Gunung Lang, Ipohwritten by jochan on 2012-04-12 #places
My husband and I took a break during the weekend and paid a visit to Gunung Lang equipped with a Lomo LC-Wide and a BeLOMO Elikon 535. Once in, we were greeted with a magnificent lake enclosed by majestic limestone outcrops surmounted by lush greenery. Across the lake lies a landscaped park that is only accessible by boat. Fortunately, a jetty provides ferry services through water taxis for visitors like us to reach the park.3 Share Tweet
Köln - Aachener Weiherwritten by stinketier on 2008-12-04 #places
The Aachener Weiher is close to the city centre of Cologne. It's a small pond with some trees and green space around, but also very close to a street.1 1 Share Tweet
Kensington Gardenswritten by littlekoala on 2011-03-14 #places
These gardens are a small paradise inside the busy and crowded city. If you want to scape from the madness of a big city, just take your camera and relax.1 Share Tweet
Schloss Benrath (Düsseldorf)written by scorpie on 2008-12-13 #places
Schloss Benrath is a palace with a huge park and garden areal. It's in the south of Düsseldorf, near the Rhine. Built in the second half of the 18th century as a summer and hunting residence for the Elector Palatine Carl Theodor von der Pfalz, it replaced an old moated castle.Share Tweet


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Saturday, February 27, 2010
HOOPMOBILES today
If you have been checking this blog out you might wonder about HOOP
(also known as Stephen Douglas Hooper) aka HI TEK HOOP.
Have to take a trip to the big building where they cut you up Monday.
If there's somethin' left of me I'll continue to blog - otherwise ? ? ?
Check out my crazy life - http://hoopmobiles.blogspot.com/
Posted by Stephen Douglas Hooper at 12:01 AM
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text:
UPDATE May 29: Portland's Colin O'Brady has finished the Explorers Grand Slam in World Record time.
He climbed Mt. Vinson (Antarctica), Aconcagua (South America), Kilimanjaro (Africa), Carstensz Pyramid (Australia/Oceania), Mt. Elbrus (Europe), Mt. Everest (Asia), and Denali (North America).
Beginning with Mt. Vinson on January 17 and ending on May 27 on the summit of Denali, Colin completed the Seven Summits and trekked across the North and South Poles in 139 days.
The time to beat was 192 days.
UPDATE May 19: Colin O'Brady has reached the summit of Mt. Everest.
He posted the following message on his Facebook page:
Today I summited Mt. Everest! Just one month after I arrived at the North Pole. I think it's fair to say this was the most exhausting part of the entire BEYOND 7/2 project. Obviously the summit day was intense but it was the cumulative week of two attempts, two windstorms, and having to stay at Camp 3 unexpectedly...
I'm really looking forward to sharing all sorts of details about the climb, it was truly remarkable. I am back down at Camp 2 now. I could have stayed in Camp 4 but I opted to get back down low as soon as possible so I can get to base camp tomorrow and fly out of here to #Alaska and finish this project up!
The thought of climbing another mountain right now is... a little bit daunting.
Anyways, it's good to be back at Camp 2. Epic day. Tons more narrative/photos/videos to share but first and foremost I need to pass out in my tent right now and get some sleep.
Thank you so much to all the amazing people who sent me messages. All the support was just amazing. I'm so humbled and grateful.
Bedtime here at 21,000ft. Hard to believe I was at 29,000ft today. Crazy.
UPDATE May 13: O'Brady is climbing Mt. Everest. High winds have delayed his climb to the summit. He hopes to reach the summit sometime this weekend.
UPDATE Feb. 9: O'Brady summited Mt. Kilimanjaro, Africa's tallest mountain, in less than 12 hours. He's 4 for 4 on the Beyond 7/2 challenge. He's crossed one pole and reached three of the seven summits. Next up is the Carstensz Pyramid.
UPDATE Feb. 1: O'Brady summited Aconcagua, the tallest mountain in South America at 22,841 feet. It's twice the height of Mt. Hood.
He moves on to Australia to climb Carstensz.
Original story from Jan. 22 below.
PORTLAND, Ore. — Endurance athlete Colin O'Brady is taking on a new challenge.
He's started what's called the 'Explorers Grand Slam.' The goal is to climb the highest mountain on each of the seven continents and trek across the north and south poles.
The climbs include Mt. Everest, and he wants to accompilsh the feat in five months. That would be a new world record.
O'Brady is also trying to raise $1 million for The Alliance for a Healthier Generation.
He just finished one section in the South Pole and is now in South America.
O'Brady started his endurance athletic career as a triathlete after being seriously burned in an accident eight years ago. He was told he might never walk again but did recover.
O'Brady spent six years as a pro triathlete but decided to make a change.
"Triathlon was beginning to feel personally self serving," he said.
Before he left, O'Brady visited several schools including Beverly Cleary in Portland.
Eleanor Warner, a student at Beverly Cleary, said, "I think it's really amazing he set a giant goal for himself."
The students are following O'Brady's blog of the trip.


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'Ptrish40' (AKA Patty of the "Zentangle Inspired Art" Yahoo group) posted a challenge involving Venn diagrams and intersecting/combining tangles. She dubbed it "VennTangles". Sounds scientificky, no?
Once I'd grasped the concept of the pencil string (last spring at the CZT seminar), I've loved the way tangle patterns morph into other patterns. This can be particularly cool when the tangles share structural elements. Oops, getting sciency there. Anyway, I decided to see what morphing might take place with this Venn idea for combining patterns.
I did the first one on a Zentangle tile. I tried to make it easy on myself by choosing tangles all based on a grid: Cubine, Dex, and Florez (by Andrea Schuman).
Using only two circles was going rather well so I decided to take another shot at three circles. But that center really was too small. I used a Zentangle tile again, but this time I used a larger circle template and ran them all off the edge. I chose some simple and fairly basic tangles: Hollibaugh, N'zeppel, and Tipple. It's quite a development from my first attempt!
What a marvelous idea! I've discovered a whole new way for tangles to work together! Thanks Patty/ptrish!!! Must. Do. More...


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Defining transformation, let alone transformational change, is a bit of a conundrum.
News & Ideas: WIT
Video Alert: What is Transformation?
Welcome to Our New Website and Blog!
The STP team has been hard at work all spring and summer, and we're thrilled to unveil our new website and blog to our community of changemakers/organizations, and those who support them!


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5/8" compression elbow for Underhill MicroEase drip irrigation kits
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text: Doing a 14-50 outlet is as simple as it gets. Don't make the mistake or assumption others make. If you want to know what is going to get approved then call your local inspector a the building dept. I have been on dozens of inspections that are rejected based on assumption and inexperienced electricians.