The universal expression for the amplitude square in quantum electrodynamics

The universal expression for the amplitude square |u_f M u_i|^2 for any matrix of interaction M is derived. It has obvious covariant form. It allows the avoidance of calculation of products of the Dirac's matrices traces and allows easy calculation of cross-sections of any different processes with polarized and unpolarized particles.Comment: 4 page

A highly strained nuclear conformation of the exportin Cse1p revealed by molecular dynamics simulations

SummaryTo investigate the stability of the open nuclear state of the exportin Cse1p and its closing mechanism at the atomic level, we have performed multiple molecular dynamics simulations. The simulations revealed a strikingly fast transition of Cse1p from the open conformation to the closed cytoplasmic form, consistent with the proposal that Cse1p represents a “spring-loaded molecule.” The structure of the ring-shaped state obtained in the simulations is remarkably close to the crystal structure of the cytoplasmic state, though the open nuclear structure was used as the only input. The conformational change is initially driven by release of strain due to RanGTP/importin-α binding. Subsequently, a stable closed state is formed, driven by attraction of electrostatically complementary interfaces. These results are consistent with and extend previous proposals. Reverse-charge and neutral mutants remained in an open state. The simulations predict a detailed reaction pathway and resolve the role of suggested hinge regions

Influence of Anti-Lymphocyte Serum on Skin Histamine in Mice

Injections of anti-lymphocyte serum markedly reduced skin histamine in mice ten weeks after treatment. This decrease is compared with the similar decrease found after treatment with glucocorticoids. Although the effect may simply reflect a rather general action on body processes, it is suggested that these immunosuppressive agents may in part act by their effects on histamine

Treatment and Burden of Disease in a Cohort of Patients with Prurigo Nodularis:A Survey-based Study

Prurigo nodularis is a pruritic dermatosis with poor treatment options. To describe treatment patterns, comorbidities, pruritus, and quality of life a survey was administered to 92 patients with prurigo nodularis. A total of 52 patients completed the survey. The most frequently used treatments were topical corticosteroids, which were prescribed to 49/52 patients, with positive effect in 13/49. A total of 46/52 patients were treated with ultraviolet B, and 9/46 reported a positive effect. A positive effect was reported for topical corticosteroids under occlusion in 21/40, for zinc dressing treatment in 17/37, for steroid injection in 9/14, for methotrexate in 5/16, and for thalidomide in 4/12 of treated patients. Thirty-six patients reported a Pittsburgh Sleep Quality Index >5, indicating poor sleep. Patients with prurigo nodularis are severely bothered by pruritus negatively affecting quality of life. Various treatments are prescribed; most frequently topical corticosteroids and ultraviolet B. Surprisingly, patients reported topical corticosteroids under occlusion, zinc-dressing treatment and steroid injection as the most effective

Data-driven derivation of molecular substructures that enhance drug activity in Gram-negative bacteria

[Image: see text] The complex cell envelope of Gram-negative bacteria creates a formidable barrier to antibiotic influx. Reduced drug uptake impedes drug development and contributes to a wide range of drug-resistant bacterial infections, including those caused by extremely resistant species prioritized by the World Health Organization. To develop new and efficient treatments, a better understanding of the molecular features governing Gram-negative permeability is essential. Here, we present a data-driven approach, using matched molecular pair analysis and machine learning on minimal inhibitory concentration data from Gram-positive and Gram-negative bacteria to uncover chemical features that influence Gram-negative bioactivity. We find recurring chemical moieties, of a wider range than previously known, that consistently improve activity and suggest that this insight can be used to optimize compounds for increased Gram-negative uptake. Our findings may help to expand the chemical space of broad-spectrum antibiotics and aid the search for new antibiotic compound classes

A cooperative knock-on mechanism underpins Ca2+-selective cation permeation in TRPV channels

The selective exchange of ions across cellular membranes is a vital biological process. Ca2+-mediated signaling is implicated in a broad array of physiological processes in cells, while elevated intracellular concentrations of Ca2+ are cytotoxic. Due to the significance of this cation, strict Ca2+ concentration gradients are maintained across the plasma and organelle membranes. Therefore, Ca2+ signaling relies on permeation through selective ion channels that control the flux of Ca2+ ions. A key family of Ca2+-permeable membrane channels is the polymodal signal-detecting transient receptor potential (TRP) ion channels. TRP channels are activated by a wide variety of cues including temperature, small molecules, transmembrane voltage, and mechanical stimuli. While most members of this family permeate a broad range of cations non-selectively, TRPV5 and TRPV6 are unique due to their strong Ca2+ selectivity. Here, we address the question of how some members of the TRPV subfamily show a high degree of Ca2+ selectivity while others conduct a wider spectrum of cations. We present results from all-atom molecular dynamics simulations of ion permeation through two Ca2+-selective and two non-selective TRPV channels. Using a new method to quantify permeation cooperativity based on mutual information, we show that Ca2+-selective TRPV channel permeation occurs by a three-binding site knock-on mechanism, whereas a two-binding site knock-on mechanism is observed in non-selective TRPV channels. Each of the ion binding sites involved displayed greater affinity for Ca2+ over Na+. As such, our results suggest that coupling to an extra binding site in the Ca2+-selective TRPV channels underpins their increased selectivity for Ca2+ over Na+ ions. Furthermore, analysis of all available TRPV channel structures shows that the selectivity filter entrance region is wider for the non-selective TRPV channels, slightly destabilizing ion binding at this site, which is likely to underlie mechanistic decoupling.</p

Enquête: Når virkningsløse behandlinger virker

Enquête: Når virkningsløse behandlinger virker &nbsp

Kristalline und gitterangepasste Ba 0.7 Sr 0.3 O-Schichten auf ebenen und vizinalen Si(001)-Oberflächen

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