Past world economic production constrains current energy demands: Persistent scaling with implications for economic growth and climate change mitigation.

Climate change has become intertwined with the global economy. Here, we describe the contribution of inertia to future trends. Drawing from thermodynamic principles, and using 38 years of available statistics between 1980 to 2017, we find a constant scaling between current rates of world primary energy consumption [Formula: see text] and the historical time integral W of past world inflation-adjusted economic production Y, or [Formula: see text]. In each year, over a period during which both [Formula: see text] and W more than doubled, the ratio of the two remained nearly unchanged, that is [Formula: see text] Gigawatts per trillion 2010 US dollars. What this near constant implies is that current growth trends in energy consumption, population, and standard of living, perhaps counterintuitively, are determined by past innovations that have improved the economic production efficiency, or enabled use of less energy to transform raw materials into the makeup of civilization. Current observed growth rates agree well with predictions derived from available historical data. Future efforts to stabilize carbon dioxide emissions are likely also to be constrained by the contributions of past innovation to growth. Assuming no further efficiency gains, options look limited to rapid decarbonization of energy consumption through sustained implementation of at least one Gigawatt of renewable or nuclear power capacity per day. Alternatively, with continued reliance on fossil fuels, civilization could shift to a steady-state economy, one that devotes economic production exclusively to maintining ongoing metabolic needs rather than to material expansion. Even if such actions could be achieved immediately, energy consumption would continue at its current level, and atmospheric carbon dioxide concentrations would only begin to balance natural sinks at concentrations exceeding 500 ppmv.

Enantioselective Synthesis of 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) via Enzymatic Desymmetrization.

An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features of stereocontrol include construction of the fully substituted 4'-carbon via a biocatalytic desymmetrization of 2-hydroxy-2-((triisopropylsilyl)ethynyl)propane-1,3-diyl diacetate and a Noyori-type asymmetric transfer hydrogenation to control the stereochemistry of the 3'-hydroxyl bearing carbon. The discovery of a selective crystallization of an N-silyl nucleoside intermediate enabled isolation of the desired ß-anomer from the glycosylation step.

DNA visualization in single molecule studies carried out with optical tweezers: Covalent versus non-covalent attachment of fluorophores.

In this study, we investigated the use of the covalent attachment of fluorescent dyes to double-stranded DNA (dsDNA) stretched between particles using optical tweezers (OT) and compared the mechanical properties of the covalently-functionalized chain to that of unmodified DNA and to DNA bound to a previously uncharacterized groove-binder, SYBR-gold. Modified DNA species were obtained by covalently linking azide-functionalized organic fluorophores onto the backbone of DNA chains via the alkyne moieties of modified bases that were incorporated during PCR. These DNA molecules were then constructed into dumbbells by attaching polystyrene particles to the respective chain ends via biotin or digoxigenin handles that had been pre-attached to the PCR primers which formed the ends of the synthesized molecule. Using the optical tweezers, the DNA was stretched by separating the two optically trapped polystyrene particles. Displacements of the particles were measured in 3D using an interpolation-based normalized cross-correlation method and force-extension curves were calculated and fitted to the worm-like chain model to parameterize the mechanical properties of the DNA. Results showed that both the contour and persistence length of the covalently-modified dsDNAs were indistinguishable from that of the unmodified dsDNA, whereas SYBR-gold binding perturbed the contour length of the chain in a force-dependent manner.

Enantioselective synthesis of ß-aryloxycarboxylic esters via asymmetric hydrogenation of ß-aryloxy-α,ß-unsaturated esters.

A novel synthesis of ß-aryloxycarboxylic esters via asymmetric hydrogenation of the corresponding ß-aryloxy-α,ß-unsaturated esters has been demonstrated. Bis(norbornadiene)rhodium(I) tetrafluoroborate (1 mol %) and Walphos W008-1 were used to generate the saturated products with high enantioselectivity and in high yield. The tolerability of the reaction to a diverse range of substituents on the aromatic ring was also explored.

Multipoint viscosity measurements in microfluidic channels using optical tweezers.

We demonstrate the technique of multipoint viscosity measurements incorporating the accurate calibration of micron sized particles. We describe the use of a high-speed camera to measure the residual motion of particles trapped in holographic optical tweezers, enabling us to calculate the fluid viscosity at multiple points across the field-of-view of the microscope within a microfluidic system.

Independent polarisation control of multiple optical traps.

We present a system which uses a single spatial light modulator to control the spin angular momentum of multiple optical traps. These traps may be independently controlled both in terms of spatial location and in terms of their spin angular momentum content. The system relies on a spatial light modulator used in a "split-screen" configuration to generate beams of orthogonal polarisation states which are subsequently combined at a polarising beam splitter. Defining the phase difference between the beams with the spatial light modulator enables control of the polarisation state of the light. We demonstrate the functionality of the system by controlling the rotation and orientation of birefringent vaterite crystals within holographic optical tweezers.

Measuring the accuracy of particle position and force in optical tweezers using high-speed video microscopy.

We assess the performance of a CMOS camera for the measurement of particle position within optical tweezers and the associated autocorrelation function and power spectrum. Measurement of the displacement of the particle from the trap center can also be related to the applied force. By considering the Allan variance of these measurements, we show that such cameras are capable of reaching the thermal limits of nanometer and femtonewton accuracies, and hence are suitable for many of the applications that traditionally use quadrant photodiodes. As an example of a multi-particle measurement we show the hydrodynamic coupling between two particles.

Molecular cloning, phylogeny and localization of AgNHA1: the first Na+/H+ antiporter (NHA) from a metazoan, Anopheles gambiae.

We have cloned a cDNA encoding a new ion transporter from the alimentary canal of larval African malaria mosquito, Anopheles gambiae Giles sensu stricto. Phylogenetic analysis revealed that the corresponding gene is in a group that has been designated NHA, and which includes (Na+ or K+)/H+ antiporters; so the novel transporter is called AgNHA1. The annotation of current insect genomes shows that both AgNHA1 and a close relative, AgNHA2, belong to the cation proton antiporter 2 (CPA2) subfamily and cluster in an exclusive clade of genes with high identity from Aedes aegypti, Drosophila melanogaster, D. pseudoobscura, Apis mellifera and Tribolium castaneum. Although NHA genes have been identified in all phyla for which genomes are available, no NHA other than AgNHA1 has previously been cloned, nor have the encoded proteins been localized or characterized. The AgNHA1 transcript was localized in An. gambiae larvae by quantitative real-time PCR (qPCR) and in situ hybridization. AgNHA1 message was detected in gastric caeca and rectum, with much weaker transcription in other parts of the alimentary canal. Immunolabeling of whole mounts and longitudinal sections of isolated alimentary canal showed that AgNHA1 is expressed in the cardia, gastric caeca, anterior midgut, posterior midgut, proximal Malpighian tubules and rectum, as well as in the subesophageal and abdominal ganglia. A phylogenetic analysis of NHAs and KHAs indicates that they are ubiquitous. A comparative molecular analysis of these antiporters suggests that they catalyze electrophoretic alkali metal ion/hydrogen ion exchanges that are driven by the voltage from electrogenic H+ V-ATPases. The tissue localization of AgNHA1 suggests that it plays a key role in maintaining the characteristic longitudinal pH gradient in the lumen of the alimentary canal of An. gambiae larvae.

Practical asymmetric synthesis of a gamma-secretase inhibitor exploiting substrate-controlled intramolecular nitrile oxide-olefin cycloaddition.

A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with > or = 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.

Direct measurement of the skew angle of the Poynting vector in a helically phased beam.

We measure the local skew angle of the Poynting vector within a helically-phased, exp (il phi), beam using a Shack Hartmann wavefront sensor. It is the skew angle of the Poynting vector with respect to the beam axis that gives rise to the orbital angular momentum of a light beam. We confirm that this skew angle is l/kr, corresponding to an orbital angular momentum of l? per photon. Measurement of orbital angular momentum in this way is an alternative to interferometric techniques giving a non-ambiguous result to both the magnitude and sign of l from a single measurement, without any restriction on the optical bandwidth.

Practical asymmetric synthesis of a non-peptidic alphavbeta3 antagonist.

The development of a practical and highly convergent synthesis of an alpha(v)beta3 antagonist is described. The two key fragments present in this compound, a tetrahydropyrido[2,3-b]azepine ring system and a chiral 3-aryl-5-oxopentanoic acid, were constructed independently and then coupled at a late stage using a Wittig reaction. The pyridoazepine moiety was prepared from N-Boc 6-chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in situ cyclization. A Suzuki reaction was then used to attach the propionaldehyde side-chain required for Wittig coupling. The coupling partner was prepared from asymmetric methanolysis of a 3-substituted glutaric anhydride followed by elaboration of the acid moiety to the requisite beta-keto phosphorane. Using this route, kilogram quantities of the desired drug candidate were prepared.

Stereoselective total syntheses and reassignment of stereochemistry of the freshwater cyanobacterial hepatotoxins cylindrospermopsin and 7-epicylindrospermopsin.

A stereoselective total synthesis of the structure 1 proposed for the freshwater cyanobacterial heptatotoxin cylindrospermopsin has been accomplished in approximately 30 operations starting from commercially available 4-methoxypyridine. Utilizing methodology developed by Comins, the tetrasubstituted piperidine A-ring unit of the hepatotoxin was efficiently constructed. The two remaining stereocenters in the natural product were then set by a stereospecific intramolecular N-sulfinylurea Diels-Alder cyclization/Grignard ring opening/allylic sulfoxide [2,3]-sigmatropic rearrangement sequence previously developed in these laboratories, leading to key intermediate 29. The stereochemical assignment of alcohol 29, which contains all six of the stereogenic centers of the natural product, was confirmed by an X-ray crystal structure determination of a derivative. Installation of the D-ring uracil moiety was effected by using our new methodology developed for this purpose, and construction of the C-ring guanidine completed the total synthesis of racemic structure 1. However, the (1)H NMR data for this compound do not match that of cylindrospermopsin, but instead agree with the data reported for 7-epicylindrospermopsin, a minor toxic metabolite that co-occurs with cylindrospermopsin. Therefore, we propose a revision of the stereochemical assignments of these natural products such that cylindrospermopsin is now represented as structure 2 and 7-epicylindrospermopsin is 1. This reassignment was further confirmed by Mitsunobu inversion of the C-7 alcohol 51 to epimer 52, and conversion of this compound to tetracyclic diol 57, which has previously been transformed to cylindrospermopsin (2).