Antibacterial Natural Products in Medicinal Chemistry—Exodus or Revival?

To create a drug, nature's blueprints often have to be improved through semisynthesis or total synthesis (chemical postevolution). Selected contributions from industrial and academic groups highlight the arduous but rewarding path from natural products to drugs. Principle modification types for natural products are discussed herein, such as decoration, substitution, and degradation. The biological, chemical, and socioeconomic environments of antibacterial research are dealt with in context. Natural products, many from soil organisms, have provided the majority of lead structures for marketed anti-infectives. Surprisingly, numerous "old" classes of antibacterial natural products have never been intensively explored by medicinal chemists. Nevertheless, research on antibacterial natural products is flagging. Apparently, the "old fashioned" natural products no longer fit into modern drug discovery. The handling of natural products is cumbersome, requiring nonstandardized workflows and extended timelines. Revisiting natural products with modern chemistry and target-finding tools from biology (reversed genomics) is one option for their revival.     

Hamilton-Jacobi theory for continuation of magnetic field across a toroidal surface supporting a plasma pressure discontinuity

The vanishing of the divergence of the total stress tensor (magnetic plus kinetic) in a neighborhood of an equilibrium plasma containing a toroidal surface of discontinuity gives boundary and jump conditions that strongly constrain allowable continuations of the magnetic field across the surface. The boundary conditions allow the magnetic fields on either side of the discontinuity surface to be described by surface magnetic potentials, reducing the continuation problem to that of solving a Hamilton-Jacobi equation. The characteristics of this equation obey Hamiltonian equations of motion, and a necessary condition for the existence of a continued field across a general toroidal surface is that there exist invariant tori in the phase space of this Hamiltonian system. It is argued from the Birkhoff theorem that existence of such an invariant torus is also, in general, sufficient for continuation to be possible. An important corollary is that the rotational transform of the continued field on a surface of discontinuity must, generically, be irrational.     

Regularization in quantum field theory from the causal point of view

The causal approach to perturbative quantum field theory is presented in detail, which goes back to a seminal work by Henri Epstein and Vladimir Jurko Glaser in 1973 [12]. Causal perturbation theory is a mathematically rigorous approach to renormalization theory, which makes it possible to put the theoretical setup of perturbative quantum field theory on a sound mathematical basis. Epstein and Glaser solved this problem for a special class of distributions, the time-ordered products, that fulfill a causality condition, which itself is a basic requirement in axiomatic quantum field theory. In their original work, Epstein and Glaser studied only theories involving scalar particles. In this review, the extension of the method to theories with higher spin, including gravity, is presented. Furthermore, specific examples are presented in order to highlight the technical differences between the causal method and other regularization methods, like, e.g. dimensional regularization.     

Subpicosecond hard x-ray streak camera using single-photon counting

We have developed and characterized a hard x-ray accumulating streak camera that achieves subpicosecond time resolution by using single-photon counting. A high repetition rate of 2 kHz was achieved by use of a readout camera with built-in image processing capabilities. The effects of sweep jitter were removed by using a UV timing reference. The use of single-photon counting allows the camera to reach a high quantum efficiency by not limiting the divergence of the photoelectrons.     

ChemInform Abstract: An ab initio Study of Possible Pathways in the Thermal Decomposition of NaAlH4

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

ChemInform Abstract: Cyclic Boron Clusters Enclosing Planar Hypercoordinate Cobalt,Iron, and Nickel

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Prony’s Method Under an Almost Sharp Multivariate Ingham Inequality

The parameter reconstruction problem in a sum of Dirac measures from its low frequency trigonometric moments is well understood in the univariate case and has a sharp transition of identifiability with respect to the ratio of the separation distance of the parameters and the order of moments. Towards a similar statement in the multivariate case, we present an Ingham inequality which improves the previously best known dimension-dependent constant from square-root growth to a logarithmic one. Secondly, we refine an argument that an Ingham inequality implies identifiability in multivariate Prony methods to the case of commonly used max-degree by a short linear algebra argument, closely related to a flat extension principle and the stagnation of a generalized Hilbert function.     

Epistemic irrelevance in credal nets: The case of imprecise Markov trees

We focus on credal nets, which are graphical models that generalise Bayesian nets to imprecise probability. We replace the notion of strong independence commonly used in credal nets with the weaker notion of epistemic irrelevance, which is arguably more suited for a behavioural theory of probability. Focusing on directed trees, we show how to combine the given local uncertainty models in the nodes of the graph into a global model, and we use this to construct and justify an exact message-passing algorithm that computes updated beliefs for a variable in the tree. The algorithm, which is linear in the number of nodes, is formulated entirely in terms of coherent lower previsions, and is shown to satisfy a number of rationality requirements. We supply examples of the algorithm’s operation, and report an application to on-line character recognition that illustrates the advantages of our approach for prediction. We comment on the perspectives, opened by the availability, for the first time, of a truly efficient algorithm based on epistemic irrelevance.     

Explaining the visible and near-infrared circular dichroism spectra of light-harvesting 1 complexes from purple bacteria: a modeling study

In this work, we investigate the origin and characteristics of the circular dichroism (CD) spectrum of various light-harvesting 1 (LH1) complexes. The near-infrared (NIR) CD signal of these core antennae is strongly nonconservative, and the nature of this nonconservativity is under examination in this paper. So far, on the basis of the high-resolution structures of LH2, we have been able to model the absorption and CD spectra in the bacteriochlorophyll (BChl) Q(Y) and Q(X) regions of LH2 (Georgakopoulou et al., Biophys. J. 2002, 82, 2184-2197), as well as in the carotenoid region (Georgakopoulou et al., Biophys. J. 2004, 87, 3010-3022). We proceed by applying the same modeling method in order to reproduce the LH1 spectra. We assume a ring of dimers in a perfect circular arrangement with 16-fold symmetry, and account for all excitonic interactions within the ring. Because LH1 complexes exhibit Q(Y) and Q(X) CD signals of very low intensity, higher transitions can easily affect these regions. Therefore, we expand the model and take into account also the Soret and carotenoid transitions. We can now understand the shape of the absorption and CD spectra and contemplate the structure of the LH1 complex. The latter is similar to LH2 in that it is a very symmetric ring dominated by excitonic interactions. The larger number of symmetry and the bigger diameter of LH1, combined with small rotations of the BChl transition dipole moments, are responsible for the display of CD signals that are very low in intensity. The interaction of the Q(Y) with the carotenoid transitions results in complete loss of the conservativity. Interaction energies between all the pigments in the ring are calculated, and their values are in good accordance with what is reported in the literature.     

Reversible activation of diblock copolymer monolayers at the interface by pH modulation, 2: Membrane interactions at the solid/liquid interface

A monolayer of the pH-responsive poly[2-(dimethylamino)ethyl methacrylate-block-methyl methacrylate] diblock copolymer [PDMAEMA-PMMA] was transferred from the air/water interface to a silicon substrate for evaluation as a tunable interlayer between biological material and solid substrates. Specular neutron reflectivity experiments revealed that the weak polyelectrolyte PDMAEMA chains at the solid/liquid interface can be reversibly activated by pH modulation. The thickness, scattering length density, and surface roughness of the polymer film can be systematically controlled by pH titration. As a simple model of plasma membranes, a lipid bilayer was deposited onto the polymer film. The membrane-substrate interaction was characterized by neutron reflectivity experiments, demonstrating that the membrane-substrate distance could be reversibly regulated by pH titration. These results confirm the potential of stimuli-responsive polymers for precise control of cell-surface interactions.