On Stochastic Differential Equations with Locally Unbounded Drift

We study the regularizing effect of the noise on differential equations with irregular coefficients. We present existence and uniqueness theorems for stochastic differential equations with locally unbounded drift.     

Transmembrane signal transduction by cofactor transport

Information processing and cell signalling in biological systems relies on passing chemical signals across lipid bilayer membranes, but examples of synthetic systems that can achieve this process are rare. A synthetic transducer has been developed that triggers catalytic hydrolysis of an ester substrate inside lipid vesicles in response to addition of metal ions to the external vesicle solution. The output signal generated in the internal compartment of the vesicles is produced by binding of a metal ion cofactor to a head group on the transducer to form a catalytically competent complex. The mechanism of signal transduction is based on transport of the metal ion cofactor across the bilayer by the transducer, and the system can be reversibly switched between on and off states by adding cadmium(ii) and ethylene diamine tetracarboxylic acid input signals respectively. The transducer is also equipped with a hydrazide moiety, which allows modulation of activity through covalent conjugation with aldehydes. Conjugation with a sugar derivative abolished activity, because the resulting hydrazone is too polar to cross the bilayer, whereas conjugation with a pyridine derivative increased activity. Coupling transport with catalysis provides a straightforward mechanism for generating complex systems using simple components.

Synthetic transducers transport externally added metal ion cofactors across the lipid bilayer membrane of vesicles to trigger catalysis of ester hydrolysis in the inner compartment. Signal transduction activity is modulated by hydrazone formation.     

Liposaccharide-based nanoparticulate drug delivery system

A series of anionic liposaccharide derivatives were synthesized in order to develop a system, which would have the capacity to act as an absorption enhancer and to improve oral bioavailability of drugs. The addition of a liposaccharide to a drug enhances drug stability against enzymatic degradation, while the lipophilicity can be controlled by variation of the lipid side chain. All liposaccharide derivatives were purified and fully characterized by nuclear magnetic resonance and high-resolution mass spectrometry. The thermodynamic profiles, critical aggregation concentrations and size of the synthesized liposaccharides were determined by isothermal titration microcalorimetry, transmission electron microscopy and dynamic light scattering. These liposaccharides formed nanoparticles with sizes below 100 nm.     

Iron deposition and inflammation in multiple sclerosis. Which one comes first?

Whether iron deposition is an epiphenomenon of the multiple sclerosis (MS) disease process or may play a primary role in triggering inflammation and disease development remains unclear at this time, and should be studied at the early stages of disease pathogenesis. However, it is difficult to study the relationship between iron deposition and inflammation in early MS due to the delay between the onset of symptoms and diagnosis, and the poor availability of tissue specimens. In a recent article published in BMC Neuroscience, Williams et al. investigated the relationship between inflammation and iron deposition using an original animal model labeled as "cerebral experimental autoimmune encephalomyelitis", which develops CNS perivascular iron deposits. However, the relative contribution of iron deposition vs. inflammation in the pathogenesis and progression of MS remains unknown. Further studies should establish the association between inflammation, reduced blood flow, iron deposition, microglia activation and neurodegeneration. Creating a representative animal model that can study independently such relationship will be the key factor in this endeavor.     

Richard A. Lerner (1938–2021)—a structural biochemist and president of Scripps Institute

Structural Chemistry - Richard A. Lerner (1938-2021) was both a chemist and an MD. He investigated the structure of peptides and proteins, identified a sleep-inducing lipid, and is best known for...     

Los Alamos and “Los Arzamas”

Marking the seventieth anniversary of the Los Alamos Laboratory provides an opportunity for comparison with its Soviet counterpart, Arzamas-16 (nicknamed “Los Arzamas”). There were similarities and differences, but in their principal motivations and treatments of their scientists, they diverged irrevocably. This Editorial is based on an invited presentation on June 12, 2013, at the Norris E. Bradbury Science Museum, Los Alamos National Laboratory, in Los Alamos, New Mexico.     

Thermal oxidation of irradiated magnetic fluids and their component surfactants and dispersing oils

Magnetic fluid applications require stability under demanding conditions. Complete magnetic fluids and their component surfactants and dispersing oils were irradiated. Their subsequent thermal oxidation was characterized by chemiluminescence and DSC. Except for polyisobutylsuccinic anhydride, irradiation sensitized the components toward oxidation. The components were ranked by stability. Complete fluids were more stable than would be predicted from their components suggesting that they may be used for nuclear applications.

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Wiener Chaos and Nonlinear Filtering

The paper discusses two algorithms for solving the Zakai equation in the time-homogeneous diffusion filtering model with possible correlation between the state process and the observation noise. Both algorithms rely on the Cameron-Martin version of the Wiener chaos expansion, so that the approximate filter is a finite linear combination of the chaos elements generated by the observation process. The coefficients in the expansion depend only on the deterministic dynamics of the state and observation processes. For real-time applications, computing the coefficients in advance improves the performance of the algorithms in comparison with most other existing methods of nonlinear filtering. The paper summarizes the main existing results about these Wiener chaos algorithms and resolves some open questions concerning the convergence of the algorithms in the noise-correlated setting. The presentation includes the necessary background on the Wiener chaos and optimal nonlinear filtering.     

The CO Photodissociation and Recombination Dynamics of the W172Y/F282T Ligand Channel Mutant of Rhodobacter sphaeroides aa3 Cytochrome c Oxidase

In the ligand channel of the cytochrome c oxidase from Rhodobacter sphaeroides (Rs aa₃) W172 and F282 have been proposed to generate a constriction that may slow ligand access to and from the active site. To explore this issue, the tryptophan and phenylalanine residues in Rs aa₃ were mutated to the less bulky tyrosine and threonine residues, respectively, which occupy these sites in Thermus thermophilus (Tt) ba₃ cytochrome oxidase. The CO photolysis and recombination dynamics of the reduced wild‐type Rs aa₃ and the W172Y/F282T mutant were investigated using time‐resolved optical absorption spectroscopy. The spectral changes associated with the multiple processes are attributed to different conformers. The major CO recombination process (44 μs) in the W172Y/F282T mutant is ~500 times faster than the predominant CO recombination process in the wild‐type enzyme (~23 ms). Classical dynamic simulations of the wild‐type enzyme and double mutant showed significant structural changes at the active site in the mutant, including movement of the heme a₃ ring‐D propionate toward Cu_B and reduced binuclear center cavity volume. These structural changes effectively close the ligand exit pathway from the binuclear center, providing a basis for the faster CO recombination in the double mutant.