Of Ghosts, Gauge Volumes, and Gauss's Law

The relationship between the canonical operator and the path integral formulation of quantum electrodynamics is analyzed with a particular focus on the implementation of gauge constraints in the two approaches. The removal of gauge volumes in the path integral is shown to match with the presence of zero-norm ghost states associated with gauge transformations in the canonical operator approach. The path integrals for QED in both the Feynman and the temporal gauges are examined and several ways of implementing the gauge constraint integrations are demonstrated. The upshot is to show that both the Feynman and the temporal gauge path integrals are equivalent to the Coulomb gauge path integral, matching the results developed by Kurt Haller using the canonical formalism. In addition, the Faddeev–Popov form for the Feynman gauge and temporal gauge Lagrangian path integrals are derived from the Hamiltonian form of the path integral.     

Ethanol/water solutions as certified reference materials for breath alcohol analyzer calibration

The Federal Institute for Materials Research and Testing (BAM), Germany, has issued a series of large volume ethanol in water certified reference materials (CRMs), primarily developed for the calibration of evidential breath alcohol analyzers in Germany. The certified parameter is the ethanol mass concentration at 20 °C. When used in a wet bath simulator, the solutions deliver gas samples that meet the requirements set by the Organization of Legal Metrology for calibration of breathalyzers. The materials were prepared gravimetrically by spiking of ethanol into water in single 5 L units. A complete uncertainty budget for the preparation process has been established. The purity of the commercial ethanol stock solution was identified to be the main source of uncertainty. For stability and homogeneity measurements and for the verification of the gravimetric mass concentration of the CRMs, a robust high-precision gas chromatography, with flame-ionization detection method for ethanol determination in aqueous samples was developed and validated. The good performance of this method has been demonstrated in several international comparisons organized by the Consultative Committee for Amount of Substance—Metrology in Chemistry at the International Bureau of Weights and Measures.     

Beta–neutrino correlation experiments on laser trapped 38mK, 37K

Laser trapping and cooling techniques are now being applied to the study of nuclear β-decay at several labs. A magneto-optical trap (MOT) provides a localized source of atoms suspended in space, so the low-energy recoiling nuclei can freely escape and be detected in coincidence with the β. This allows reconstruction of the neutrino momentum, and the deduction of the β-v correlation in a more direct fashion than previously possible. In addition, the nuclei can be polarized by atomic techniques, opening a new class of spin correlation measurements to test the degree to which parity is maximally violated in the weak interaction. Our present experiment has detected several hundred thousand recoil-β⁺ coincidences from the 0⁺ → 0⁺ pure Fermi decay of ^38mK, produced at the on-line isotope separators TISOL and ISAC at TRIUMF. Our goal is to set constraints on non-Standard Model scalar bosons competitive with high-energy colliders and more conventional β-v correlation experiments. This revised version was published online in August 2006 with corrections to the Cover Date.     

Decomposition of overlapping plasmagram peaks by spectral subtraction

Low field atmospheric pressure Ion Mobility Spectroscopy (IMS) involves the careful analysis of plasmagrams with multiple peaks which can mask one another when they are closely spaced in drift time or corresponding reduced mobility. A typical signal processing approach to decomposing overlapped peaks would be to use an orthogonal decomposition technique, but unfortunately Gaussian-like functions are not orthogonal, so no unique decomposition can be guaranteed. However, each ion species in the drift tube will arrive at the Faraday plate with a known statistical distribution determined by the IMS instrument’s drift tube design, electric field strength, reagent gas flow and other instrument-specific factors such as the ion gate function. This paper presents a straightforward algorithm for decomposing plasmagrams into distinct peaks using a subtractive technique that independently estimates the statistical parameters of each peak, rejecting spurious peaks and electrical noise. The results show that for relatively short gate times, the plasmagram peaks are nearly Gaussian-shaped, but slightly fatter and asymmetric. We show that including of the gate rise and fall times is also significant in matching the plasmagram peak shape. We also show that the diffusion effects on resolution can be attributed to combinations of non-uniform ion distributions in the reaction chamber as well as detritus effects in the drift tube. Given the known peaks statistical parameters, one can then separate overlapping peaks using a straightforward spectral subtractive technique.     

On the mechanism of liquid metal ion sources

We have developed a theoretical model of liquid metal ion source operation which consistently explains the shape and size of the ion emitting region, the mechanism of ion formation and properties of the ion beam. We find that field evaporation is the main current generating mechanism and that field evaporation and subsequent postionization produce the doubly and higher charged ions. Field ionization of thermally evaporated neutrals may make a significant, but not dominant, contribution to the current of singly charged ions. Our model is consistent with experimental results on energy spread, energy deficit and charge state ratios and we are able to explain the stability of the emitted ion current.     

In vitro evolution of ligands to the membrane protein caveolin

Membrane proteins comprise a third of the human genome, yet present challenging targets for reverse chemical genetics. For example, although implicated in numerous diseases including multiple myeloma, the membrane protein caveolin-1 appears to offer a poor target for the discovery of synthetic ligands due to its largely unknown structure and insolubility. To break this impasse and identify new classes of caveolae controlling lead compounds, we applied phage-based, reverse chemical genetics for the discovery of caveolin-1 ligands derived from the anti-HIV therapeutic T20. Substitution of homologous residues into the T20 sequence used a process analogous to medicinal chemistry for the affinity maturation to bind caveolin. The resultant caveolin-1 ligands bound with >1000-fold higher affinity than wild-type T20. Two types of ELISAs and isothermal titration calorimetry (ITC) measurements demonstrated high affinity binding to caveolin by the T20 variants with K(d) values in the 150 nM range. Microscopy experiments with the highest affinity caveolin ligands confirmed colocalization of the ligands with endogenous caveolin in NIH 3T3 cells. The results establish the foundation for targeting caveolin and caveolae formation in living cells.     

Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design

LpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against gram-negative infections.