Computing the nonabelian tensor squares of polycyclic groups

In this paper we develop a theory for computing the nonabelian tensor square and related computations for finitely presented groups and specialize it to polycyclic groups. This theory provides a framework for making nonabelian tensor square computations for polycyclic groups and is the basis of an algorithm for computing the nonabelian tensor square for any polycyclic group.     

Accuracy of SUPREX (stability of unpurified proteins from rates of H/D exchange) and MALDI mass spectrometry-derived protein unfolding free energies determined under non-EX2 exchange conditions

Described here is the impact of so-called non-EX2 exchange behavior on the accuracy of protein unfolding free energies (i.e., DeltaG u values) and m values (i.e.,-deltaDeltaG u/delta[denaturant] values) determined by an H/D exchange and mass spectrometry-based technique termed stability of unpurified proteins from rates of H/D exchange (SUPREX). Both experimental and theoretical results on a model protein, ubiquitin, reveal that reasonably accurate thermodynamic parameters for its folding reaction can be determined by SUPREX even when H/D exchange data is collected in a non-EX2 regime. Not surprisingly, the theoretical results reported here on a series of hypothetical protein systems with a wide range of biophysical properties show that the accuracy of SUPREX-derived DeltaG u and m values is compromised for many proteins when analyses are performed at high pH (e.g., pH 9) and for selected proteins with specific biophysical parameters (e.g., slow folding rates) when analyses are performed at lower pH. Of more significance is that the experimental and theoretical results reveal a means by which problems with non-EX2 exchange behavior can be detected in the SUPREX experiment without prior knowledge of the protein's biophysical properties. The results of this work also reveal that such problems with non-EX2 exchange behavior can generally be minimized if appropriate H/D exchange times are employed in the SUPREX experiment to yield SUPREX curve transition midpoints at chemical denaturant concentrations less than 2 M.     

An efficient synthesis of a potent PPARpan agonist

An efficient synthesis of 2-{4-[({4-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)thio]phenoxy}-2-methylpropanoic acid (1), a potent PPARpan agonist, is described. The seven-step synthesis, which afforded 1 in 30% overall yield, includes a highly regioselective carbon-sulfur bond formation via coupling of a bishydroxymethylthiazole (3) with 4-hydroxythiophenol, displacement of the remaining alcohol through a three-step telescoped sequence involving an efficient cleavage of an aryl mesylate, and an efficient and practical method of introducing an isobutyric acid fragment.     

Colchicine glycorandomization influences cytotoxicity and mechanism of action

The reaction of 70 unprotected, diversely functionalized free reducing sugars with methoxyamine-appended colchicine led to the production of a 58-member glycorandomized library. High-throughput cytotoxicity assays revealed glycosylation to modulate specificity and potency. Library members were also identified which, unlike the parent natural product (a destabilizer), stabilized in vitro tubulin polymerization in a manner similar to taxol. This study highlights a simple extension of neoglycorandomization toward amine-bearing scaffolds and the potential benefit of glycosylating nonglycosylated natural products.     

COMPASS-D magnetic equilibria with lh and NBI current drive

Plasma equilibria are investigated numerically, using the ACCOME and ASTRA codes, on the COMPASS-D tokamak (R ₀ = 0:56 m, a = 0:17 m, B _T = 1:2 T, I _p = 200 kA, k = 1:7, δ_x = 0:4) for the planned Neutral Beam Injection (NBI) and Low Hybrid Current Drive (LHCD) systems. The LH system provides P _LH = 0:4 MW at n _∥ = 2:1 and f _LH = 1:3 GHz. The NBI system has two 40 keV deuterium beams in co-or counter-directions with a total power of 0.6 MW. The COMPASS-D tokamak can typically operate in two configurations-single null divertor (SND) and single null divertor with a higher triangularity (SNT). Higher triangularity provides access to higher confinement and improved stability, and leads to larger n _∥ up-shifts for better slow LH wave absorption.We investigate the range of densities n = 2 ÷ 6 × 10¹⁹ m^?3. Both the LH and NB driven currents decrease with density. The magnetic shear reverses with off-axis beam incidence. In the given plasma parameter range, typically up to 60 kA of bootstrap current is driven and with NB co-injection up to 80 kA of NB current is driven. LHCD is weak at f = 1:3 GHz and BT = 1:2 T, but at n = 3 × 10¹⁹ m^?3 the LH driven current is about 40 kA, so that the required plasma current of 200 kA is supported almost non-inductively.     

Look at data to evaluate uncertainty: a comment on “Uranium assay determination …” by Mathew et al.

In a recent paper, Mathew et al. detailed, for a specific titration-based assay of uranium, a “step-by-step approach to calculate the GUM uncertainty of the measurand”, in which their uncertainty assessment was based solely on prior knowledge, ignoring the manifest variability in their replication data. A simple analysis of the variance from their data reveals that the uncertainty in the average of the replicated quantity (TEF) was at least 3.5 times their estimate. Since the observables that contribute most to the final uncertainty in their method were not replicated, it is unknown whether the estimates for the uncertainties of those quantities, and thus of the output quantity, were also underestimated. This comment demonstrates how a better uncertainty evaluation is possible by extracting as much knowledge as possible from the extant data.     

Reconstruction of the surface power spectrum from reflectivity data

An analytical approach is used to determine the power spectrum of the surface roughness from experimental data for the reflectivity of randomly rough surfaces. A one-dimensional, randomly rough, perfectly conducting surface that is illuminated by s-polarized light whose plane of incidence is perpendicular to the generators of the surface is considered, and the power spectrum is obtained within the framework of phase perturbation theory. Good agreement with numerically generated experimental data is obtained.     

Extended hückel calculations of negative spin density

Extended Hückel molecular orbital calculations have been performed on the vinyl radical (C₂H₃·) for a variety of geometries. The net spin densities for the protons have been calculated using a formalism due to McLachlan from the parameters of the Extended Hückel molecular orbital calculations. This calculation includes contributions from the positive spin density at the nucleus and spin polarization contributions, which are weighted by a semi-empirical parameter. This is in contrast to the usual Extended Hückel calculation which is incapable of calculating negative spin densities.The results of our calculations are compared with other calculations on this system and the experimental values for the isotropic hyperfine coupling constants.

---

Zusammenfassung Rechnungen im Rahmen der erweiterten Hückeltheorie sind für verschiedene Geometrien des Vinylradikals durchgeführt worden. Die Spindichten am Ort der Protonen sind nach McLachlan's Formalismus bestimmt worden und schließen sowohl Beiträge der positiven Spindichte zum Kern als auch solche infolge Spinpolarisation, die mit einem semiempirischen Faktor behaftet sind, ein — im Gegensatz zur gewöhnlichen Hückeltheorie, die niemals negative Spindichten ergibt.Die Resultate werden mit denen anderer Rechnungen und experimentellen isotropen HFS-Kopplungskonstanten verglichen.

---

Résumé Des calculs en méthode de Hückel étendue ont été faits sur le radical vinyle pour différentes géométries. Les densités de spin pour les protons ont été calculées en utilisant un formalisme de McLachlan. Les calculs incluent les contributions des densités de spin positives au noyau et les contributions de polarisation de spin, pondérées par un paramètre semi-empirique. Cela contraste avec les calculs Hückel étendus usuels qui ne peuvent pas calculer de densités de spin négatives.Les résultats sont comparés avec d'autres calculs sur ces systèmes et aux valeurs expérimentales pour les constantes de couplage hyperfins isotropes.

     

An efficient multigram synthesis of the potent histamine H3 antagonist GT-2331 and the reassessment of the absolute configuration

GT-2331 is a potent histamine H(3) antagonist which has entered clinical trials. Efficient multigram syntheses of this compound and its enantiomer are described. The literature reports that GT-2331 is the dextrorotatory (+), more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole with the absolute configuration of (1R,2R)-1. However, we found that the dextrorotatory, more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole has the (1S,2S) absolute configuration. We suggest a reconsideration of the absolute configuration of GT-2331.     

Mapping tertiary interactions in protein folding reactions: a novel mass spectrometry- and chemical synthesis-based approach

A novel mass spectrometry- and chemical synthesis-based approach for studying protein folding reactions is described, and its initial application to study the folding/unfolding reaction of a homo-hexameric enzyme 4-oxalocrotonate (4OT) is reported. This new approach involves the application of total chemical synthesis to prepare protein analogues that contain a photoreactive amino acid site-specifically incorporated into their primary amino acid sequence. To this end, a photoreactive amino acid-containing analogue of 4OT in which Pro-1 was replaced with p-benzoyl-l-phenylalanine (Bpa) was prepared. This analogue can be used to map structurally specific protein-protein interactions in 4OT's native folded state. These photocrosslinking studies and peptide mapping results with (PlBpa)4OT indicate that this construct is potentially useful for probing the structural properties of equilibrium and kinetic intermediates in 4OT's folding reaction.