Dorsal Skin Fold Chamber for High Resolution Multiphoton Imaging

The advantages offered by multiphoton microscopy enabled this technique to be applied for in vivo understanding of physiological processes. However, multiphoton intravital microscopy also requires associated technologies to be developed. In this work, we detailed the design of a dorsal skin fold chamber made of titanium alloy that allow high resolution multiphoton fluorescence and second harmonic generation (SHG) microscopy to be achieved. We demonstrate that our apparatus is capable of obtaining high resolution, images of blood vessels and collagen matrix in nude mice. Such an imaging chamber will allow physiological processes to be investigated at high resolution     

Spectral properties of the interference head wave

The interference head wave propagating through a sediment with a linear sound speed gradient is studied as a function of the parameter zeta, which is itself a function of acoustic frequency f, sediment sound speed and its gradient, and range. For zeta<1 the amplitude spectrum of the interference head waves goes as |S(f)|/f, where S(f) is the source spectrum. For increasing zeta beyond unity a more complicated modulation of S(f) ensues, which is explained by a channel transfer function H1(f), constructed analytically from a summation of terms involving zeroth-order refracted waves (referred to as a ray approach). For zeta greater than or approximately equal to 2 this summation compares well with a wave theory result for the interference head wave involving a fluid-fluid boundary. The amplitude spectrum of the interference head wave in the absence of sediment attenuation is |S(f)| x |H1(f)| and it is essential to know these to obtain an estimate of sediment attenuation from field observations. Examples of |S(f)| x |H1(f)| are presented for which H1(f) is computed directly using the ray approach and indirectly using the parabolic wave equation. A brief discussion on the application of these results towards the inversion of sediment attenuation is given.     

Structural determination of monoacylglycerols extracted from marine sponge by fast atom bombardment tandem mass spectrometry

Five new monoacylglycerols (MAGs) were isolated from the marine sponge Stelletta sp. by reversed-phase high-performance liquid chromatography and analyzed by positive ion fast atom bombardment mass spectrometry (FAB-MS). FAB mass spectra of these compounds produced abundant sodium-adducted molecules [M+Na]+ from a mixture of 3-nitrobenzyl alcohol and sodium iodide. The structural elucidation of these sponge MAGs was carried out by FAB tandem mass spectrometry (MS/MS). To find diagnostic ions for the characterization of the MAGs, authentic MAGs were initially analyzed by collision-induced dissociation (CID) MS/MS. The CID MS/MS of [M+Na]+ precursor ions resulted in the formation of numerous characteristic product ions via a series of dissociative processes. The product ions formed by charge-remote fragmentation (CRF) provided important information for the characterization of acyl chains substituted at the glycerol backbone, and product ions at m/z 84, 97, 113 and 139 were diagnostic for the sodiated glycerol backbone. On the basis of these fragmentation patterns, the structures of five MAGs extracted from marine sponge were elucidated. In addition, high-resolution mass measurement was performed to obtain the elemental compositions of the MAGs.     

A flexible dibenzo-O4S2-macrocycle: twist-and-squeeze type metal binding via synergic action of metal-ligand and metal-π interactions

A 21-membered O₄S₂-donor-macrocycle (L) incorporating a dibenzo-subunit was synthesized. From the reaction of L with AgPF₆, an endo-type 1:1 complex [AgL]PF₆ (1) was obtained. On complexation, the conformation of L changes dramatically due to metal-ligand coordination as well as π-interactions between the metal and the dibenzo-subunit from L. This unique change in configuration showing a twist-and-squeeze type process illustrates how large flexible ligands stabilize complexes through conformational changes.     

Regio- and stereoselectivity in the concatenated enyne cross metathesis–metallotropic [1,3]-shift of terminal 1,3-diyne

Enyne cross metathesis of terminal 1,3-diynes with various alkenes afforded two products of distinctive connectivity, as the result of a uniform mode of initiation but different modes of termination events with or without metallotropic [1,3]-shift. Steric and electronic factors of the substituents on the 1,3-diynes play an important role in controlling the metallotropic [1,3]-shift of the propagating alkylidene intermediates and their regioselective trapping to the final products.     

Periodicity in Structure,Bonding, and Reactivity for p-Block Complexes of a Geometry Constraining Triamide Ligand

The use of pincer ligands to access non-VSEPR geometries at main-group centers is an emerging strategy for eliciting new stoichiometric and catalytic reactivity. As part of this effort, several different tridentate trianionic substituents have to date been employed at a range of different central elements, providing a patchwork dataset that precludes rigorous structure–function correlation. An analysis of periodic trends in structure (solid, solution, and computation), bonding, and reactivity based on systematic variation of the central element (P, As, Sb, or Bi) with retention of a single tridentate triamide substituent is reported herein. In this homologous series, the central element can adopt either a bent or planar geometry. The tendency to adopt planar geometries increases descending the group with the phosphorus triamide ( 1 ) and its arsenic congener ( 2 ) exhibiting bent conformations, and the antimony ( 3 ) and bismuth ( 4 ) analogues exhibiting a predominantly planar structure in solution. This trend has been rationalized using an energy decomposition analysis. A rare phase-dependent dynamic covalent dimerization was observed for 3 and the associated thermodynamic parameters were established quantitatively. Planar geometries were found to engender lower LUMO energies and smaller band gaps than bent ones, resulting in different reactivity patterns. These results provide a benchmark dataset to guide further research in this rapidly emerging area.     

Chemical mimetics of the N-degron pathway alleviate systemic inflammation by activating mitophagy and immunometabolic remodeling

The Arg/N-degron pathway, which is involved in the degradation of proteins bearing an N-terminal signal peptide, is connected to p62/SQSTM1-mediated autophagy. However, the impact of the molecular link between the N-degron and autophagy pathways is largely unknown in the context of systemic inflammation. Here, we show that chemical mimetics of the N-degron Nt-Arg pathway (p62 ligands) decreased mortality in sepsis and inhibited pathological inflammation by activating mitophagy and immunometabolic remodeling. The p62 ligands alleviated systemic inflammation in a mouse model of lipopolysaccharide (LPS)-induced septic shock and in the cecal ligation and puncture model of sepsis. In macrophages, the p62 ligand attenuated the production of proinflammatory cytokines and chemokines in response to various innate immune stimuli. Mechanistically, the p62 ligand augmented LPS-induced mitophagy and inhibited the production of mitochondrial reactive oxygen species in macrophages. The p62 ligand-mediated anti-inflammatory, antioxidative, and mitophagy-activating effects depended on p62. In parallel, the p62 ligand significantly downregulated the LPS-induced upregulation of aerobic glycolysis and lactate production. Together, our findings demonstrate that p62 ligands play a critical role in the regulation of inflammatory responses by orchestrating mitophagy and immunometabolic remodeling.Subject terms: Sepsis, Mitophagy     

The Synthesis of Warfarin Using a Reconfigurable-Reactor Platform Integrated to a Multiple-Variable Optimization Tool

Optimization of the asymmetric synthesis of warfarin, an important anticoagulant, has been evaluated using a reconfigurable reaction platform capable of performing batch, continuous flow, and plug-flow synthesis. Further, this platform has been integrated with a novel, multidimensional, multiple variable analysis tool that can evaluate multiple critical quality attributes (CQA), percent conversion and enantiomeric excess in this case, from a single injection that is repeatedly recycled in a closed loop of chromatography columns, a detector and a heart-cut valve. Further, the new, integrated analysis system also facilitates validation of each QA, providing a high-level of confidence in analytical measurements, which are obtained without operator intervention.     

Revisiting a magneto-elastic strange attractor

We revisit an early example of a nonlinear oscillator that exhibits chaotic motions when subjected to periodic excitation: the magneto-elastically buckled beam. In the paper of Moons and Holmes (1980) [1] magnetic field calculations were outlined but not carried through; instead the nonlinear forces responsible for creation of a two-well potential and buckling were fitted to a polynomial function after reduction to a single mode model. In the present paper we compute the full magnetic field and use it to approximate the forces acting on the beam, also using a single mode reduction. This provides a complete model that accurately predicts equilibria, bifurcations, and free oscillation frequencies of an experimental device. We also compare some periodic, transient and chaotic motions with those obtained by numerical simulations of the single mode model, further illustrating the rich dynamical behavior of this simple electromechanical system.