Separatrix crossing and symmetry breaking in NLSE-like systems due to forcing and damping.

We theoretically and experimentally examine the effect of forcing and damping on systems that can be described by the nonlinear Schrödinger equation (NLSE), by making use of the phase-space predictions of the three-wave truncation. In the latter, the spectrum is truncated to only the fundamental frequency and the upper and lower sidebands. Our experiments are performed on deep water waves, which are better described by the higher-order NLSE, the Dysthe equation. We therefore extend our analysis to this system. However, our conclusions are general for NLSE systems. By means of experimentally obtained phase-space trajectories, we demonstrate that forcing and damping cause a separatrix crossing during the evolution. When the system is damped, it is pulled outside the separatrix, which in the real space corresponds to a phase-shift of the envelope and therefore doubles the period of the Fermi-Pasta-Ulam-Tsingou recurrence cycle. When the system is forced by the wind, it is pulled inside the separatrix, lifting the phase-shift. Furthermore, we observe a growth and decay cycle for modulated plane waves that are conventionally considered stable. Finally, we give a theoretical demonstration that forcing the NLSE system can induce symmetry breaking during the evolution.

Nonlinear wave evolution with data-driven breaking.

Wave breaking is the main mechanism that dissipates energy input into ocean waves by wind and transferred across the spectrum by nonlinearity. It determines the properties of a sea state and plays a crucial role in ocean-atmosphere interaction, ocean pollution, and rogue waves. Owing to its turbulent nature, wave breaking remains too computationally demanding to solve using direct numerical simulations except in simple, short-duration circumstances. To overcome this challenge, we present a blended machine learning framework in which a physics-based nonlinear evolution model for deep-water, non-breaking waves and a recurrent neural network are combined to predict the evolution of breaking waves. We use wave tank measurements rather than simulations to provide training data and use a long short-term memory neural network to apply a finite-domain correction to the evolution model. Our blended machine learning framework gives excellent predictions of breaking and its effects on wave evolution, including for external data.

Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain.

Rat brain cDNA and genomic clones encoding three K+ channels, Kv1, Kv2, and Kv3, have been isolated by screening with Shaker probes and encode proteins of 602, 530, and 525 amino acids. Each of the deduced protein sequences contains six hydrophobic domains (including an S4-type region characteristic of many voltage-gated channels) and are 68%-72% identical to each other overall. Transcripts of approximately 3.5, approximately 6.5, and approximately 9.5 kb encode Kv1, Kv2, and Kv3, respectively. The Kv2 mRNA is expressed only in brain, whereas the Kv1 and Kv3 transcripts are found in several other tissues as well. There is a marked increase in the amount of Kv1 mRNA in cardiac tissue during development and a similar, but less pronounced, increase of both this mRNA and the Kv2 transcript in brain. RNAs synthesized in vitro from the three clones induce voltage- and time-dependent, delayed rectifier-like K+ currents when injected into Xenopus oocytes, demonstrating that they encode functional K+ channels.

A distinct strategy to generate high-affinity peptide binders to receptor tyrosine kinases.

We describe a novel and general way of generating high affinity peptide (HAP) binders to receptor tyrosine kinases (RTKs), using a multi-step process comprising phage-display selection, identification of peptide pairs suitable for hetero-dimerization (non-competitive and synergistic) and chemical synthesis of heterodimers. Using this strategy, we generated HAPs with K(D)s below 1 nM for VEGF receptor-2 (VEGFR-2) and c-Met. VEGFR-2 HAPs bound significantly better (6- to 500-fold) than either of the individual peptides that were used for heterodimer synthesis. Most significantly, HAPs were much better (150- to 800-fold) competitors than monomers of the natural ligand (VEGF) in various competitive binding and functional assays. In addition, we also found the binding of HAPs to be less sensitive to serum than their component peptides. We believe that this method may be applied to any protein for generating high affinity peptide (HAP) binders.

Shaw-like rat brain potassium channel cDNA's with divergent 3' ends.

The complete amino acid sequence of a potassium channel protein of rat brain, Kv3.2b, plus a partial sequence of a related channel, Kv3.2c, are deduced from molecular cloning of the respective cDNA's. Kv3.2b and Kv3.2c share extensive amino acid sequence identity with a previously identified channel, RKShIIIA[1], before diverging to unique carboxy termini. Probes specific for Kv3.2b and RKShIIIA detect similarly sized mRNA's on Northern blots. These two proteins are encoded by a single gene based on genomic Southern blotting, and therefore arise by alternative splicing. In vitro transcribed mRNA for Kv3.2b induces the expression of outward K+ currents in Xenopus oocytes under voltage-clamp conditions.

Ultrastructural observations on spinal ganglion biopsy in Friedreich's ataxia: a preliminary report.

We report the preliminary study of a dorsal root ganglion obtained at biopsy during a surgical intervention in a patient with Friedreich's ataxia. There was an apparent decrease in the number of large myelinated fibers without necrosis, but with numerous axonal swellings consisting mainly of dense accumulated neurofilaments. Large amounts of lipofuscin were also found as well as some onion bulb formations suggesting a process of axonal atrophy.

Cloning and chromosomal localization of the human A2b adenosine receptor gene (ADORA2B) and its pseudogene.

To determine the chromosomal localization of the human A2b adenosine receptor, the corresponding genomic clone was isolated and used as a probe for fluorescence in situ hybridization to metaphase chromosomes. Partial sequence analysis of the A2b gene (AD-ORA2B) revealed an intron that interrupted the coding region corresponding to the second intracellular loop similar to that reported for A1 and A2a adenosine receptor genes. A pseudogene for the A2b receptor was also identified; it exhibited 79% identity to the A2b adenosine receptor cDNA coding sequence and contained multiple deletions, point mutations, and frame shifts and two in-frame stops. These changes would result in the inability to encode a functional receptor. The genomic clones were utilized to localize the A2b receptor to chromosome 17p12 and the A2b pseudogene to chromosome 1q32.

[Shunt glomerulonephritis: clinical and histopathological manifestations]. / La glomérulonéphrite de shunt: manifestations cliniques et histopathologiques.

In patients with cerebrospinal fluid internal shunts, immune complex glomerulonephritis sometimes develops. Of two new cases the first was classic, while the second was in an adult who had had a ventriculoatril shunt for 8 years; furthermore, the patient had acute renal failure and is the first to have been reported to have Peptococcus septicemia. Shunt glomerulonephritis is characterized by the following: (a) its occurrence following, most often, Staphylococcus albus infection in a patient who usually has a ventriculoatrial shunt; (b) transitory improvement of the symptoms by antibiotherapy only; and (c) full recovery if the prosthesis is removed. Laboratory studies show a low serum concentration of the C3 component of complement, the presence of cryoglobulins and a positive rheumatoid factor test. These abnormalities are reversible with removal of the prosthesis. Optical microscopy of a renal biopsy specimen in the two cases showed cellular proliferation of the glomerular tuft, electron microscopy demonstrated subepithelial deposits and immunofluorescent studies revealed intramembranous and intramesangial immune complexes. These features are similar to those observed in experimental nephritis induced in animals by foreign protein.

The failure of serum albumin to affect capillary permeability in the isolated rabbit heart.

The method of local tissue clearance was used to measure capillary permeability-surface area products (PS) for [3H]inulin and [14C]sucrose in the left ventricular wall of the isolated rabbit heart. As soon as a heart was excised, its coronary arteries were perfused with Ringer solution at 37 degrees for at least 30 min before clearance trials were begun. In paired trials, Ringer perfusion fluid containing 1% bovine serum albumin (Sigma) was compared with protein-free Ringer solution in terms of sucrose PS (PSs), inulin PS (PSi), and the PS ratio (Pi/Ps). With or without protein, the mean Pi/Ps was significantly less than the ratio of the free diffusion coefficients. With the untreated albumin, flow resistance rose markedly, and the PSs of both solutes fell but not Pi/Ps. To remove the unidentified vasoactive contaminant (which apparently resisted dialysis), the albumin was "defatted" by the procedure of R. F. Chen (1967, J. Biol. Chem. 242, 173-181). Defatted albumin (1% in the perfusion fluid) did not affect the volume of distribution (lambda) of sucrose or inulin in the myocardium, the heart rate, coronary flow, flow resistance, PSs, PSi, or Pi/Ps. Apparently bovine serum albumin does not influence capillary permeability in the rabbit heart. A protein effect on permeability, however, could have been missed if it has a long latent period (more than 15 min) or a long persistence (more than 30 min).

Transcapillary transport of solutes in the myocardium: effects of nitroglycerin, isoproterenol and histamine on permeability-surface area products of inulin and sucrose.

Three vasoactive drugs (nitroglycerin, isoproterenol and histamine) were examined for their effects on microsolute transport across capillary walls in the myocardium. Coronary arteries of the isolated rabbit heart were perfused at constant pressure with Tris-buffered Ringer's solution (pH = 7.4, 37 degrees C) with and without drug present in the perfusion fluid. A mixture of [3H]inulin and [14C]sucrose was injected into the left ventricular wall. From measured clearance rates, capillary permeability-surface area products (PS) (in milliliters per minute per 100 g) were computed for both solutes by the method of Gosselin and Stibitz (Pflügers Arch. 318: 85-98, 1970). Mean control PS values were 60.7 and 14.1 for sucrose and inulin, respectively. This computation required experimental determination of the myocardial volume of distribution (in milliliters per gram) for each reference solute. Values of myocardial volume of distribution obtained in the presence of nitroglycerin, isoproterenol and histamine did not differ significantly from controls. In paired clearance trials, isoproterenol and nitroglycerin significantly increased coronary flow, but neither drug influenced PS-inulin, PS-sucrose or the ratio PS inulin/PS sucrose. In contrast, histamine caused an apparently irreversible decrease in flow. Furthermore, in the presence of histamine, PS inulin/PS sucrose increased from 0.28 +/- 0.03 to 0.40 +/- 0.05 (P less than 0.003). This rise is consonant with a widening of diffusion channels between neighboring endothelial cells in the capillary wall. Thus, histamine (and presumably substances capable of histamine release) appears to increase myocardial permeability to microsolutes, in addition to its well known ability to enhance protein transport across postcapillary venules.

Alternative splicing contributes to K+ channel diversity in the mammalian central nervous system.

In an attempt to define the molecular basis of the functional diversity of K+ channels, we have isolated overlapping rat brain cDNAs that encoded a neuronal delayed rectifier K+ channel, K,4, that is structurally related to the Drosophila Shaw protein. Unlike previously characterized mammalian K+ channel genes, which each contain a single protein-coding exon, K,4 arises from alternative exon usage at a locus that also encodes another mammalian Shaw homolog, NGK2. Thus, the enormous diversity of K+ channels in mammals can be generated not just through gene duplication and divergence but also through alternative splicing of RNA.

Mammalian heterogeneous nuclear ribonucleoprotein A1. Nucleic acid binding properties of the COOH-terminal domain.

A1 is a core protein of the eukaryotic heterogeneous nuclear ribonucleoprotein complex and is under study here as a prototype single-stranded nucleic acid-binding protein. A1 is a two-domain protein, NH2-terminal and COOH-terminal, with highly conserved primary structure among vertebrate homologues sequenced to date. It is well documented that the NH2-terminal domain has single-stranded DNA and RNA binding activity. We prepared a proteolytic fragment of rat A1 representing the COOH-terminal one-third of the intact protein, the region previously termed COOH-terminal domain. This purified fragment of 133 amino acids binds to DNA and also binds tightly to the fluorescent reporter poly(ethenoadenylate), which is used to access binding parameters. In solution with 0.41 M NaCl, the equilibrium constant is similar to that observed with A1 itself, and binding is cooperative. The purified COOH-terminal fragment can be photochemically cross-linked to bound nucleic acid, confirming that COOH-terminal fragment residues are in close contact with the polynucleotide lattice. These binding results with isolated COOH-terminal fragment indicate that the COOH-terminal domain in intact A1 can contribute directly to binding properties. Contact between both COOH-terminal domain and NH2-terminal domain residues in an intact A1:poly(8-azidoadenylate) complex was confirmed by photochemical cross-linking.