Three-Dimensional Fermi Surface of Overdoped La-Based Cuprates.

We present a soft x-ray angle-resolved photoemission spectroscopy study of overdoped high-temperature superconductors. In-plane and out-of-plane components of the Fermi surface are mapped by varying the photoemission angle and the incident photon energy. No k_{z} dispersion is observed along the nodal direction, whereas a significant antinodal k_{z} dispersion is identified for La-based cuprates. Based on a tight-binding parametrization, we discuss the implications for the density of states near the van Hove singularity. Our results suggest that the large electronic specific heat found in overdoped La_{2-x}Sr_{x}CuO_{4} cannot be assigned to the van Hove singularity alone. We therefore propose quantum criticality induced by a collapsing pseudogap phase as a plausible explanation for observed enhancement of electronic specific heat.

Two-dimensional type-II Dirac fermions in layered oxides.

Relativistic massless Dirac fermions can be probed with high-energy physics experiments, but appear also as low-energy quasi-particle excitations in electronic band structures. In condensed matter systems, their massless nature can be protected by crystal symmetries. Classification of such symmetry-protected relativistic band degeneracies has been fruitful, although many of the predicted quasi-particles still await their experimental discovery. Here we reveal, using angle-resolved photoemission spectroscopy, the existence of two-dimensional type-II Dirac fermions in the high-temperature superconductor La1.77Sr0.23CuO4. The Dirac point, constituting the crossing of [Formula: see text] and [Formula: see text] bands, is found approximately one electronvolt below the Fermi level (EF) and is protected by mirror symmetry. If spin-orbit coupling is considered, the Dirac point degeneracy is lifted and the bands acquire a topologically non-trivial character. In certain nickelate systems, band structure calculations suggest that the same type-II Dirac fermions can be realised near EF.

Direct observation of orbital hybridisation in a cuprate superconductor.

The minimal ingredients to explain the essential physics of layered copper-oxide (cuprates) materials remains heavily debated. Effective low-energy single-band models of the copper-oxygen orbitals are widely used because there exists no strong experimental evidence supporting multi-band structures. Here, we report angle-resolved photoelectron spectroscopy experiments on La-based cuprates that provide direct observation of a two-band structure. This electronic structure, qualitatively consistent with density functional theory, is parametrised by a two-orbital ([Formula: see text] and [Formula: see text]) tight-binding model. We quantify the orbital hybridisation which provides an explanation for the Fermi surface topology and the proximity of the van-Hove singularity to the Fermi level. Our analysis leads to a unification of electronic hopping parameters for single-layer cuprates and we conclude that hybridisation, restraining d-wave pairing, is an important optimisation element for superconductivity.

Peak-power scaling of femtosecond Yb:Lu2O3 thin-disk lasers.

We present a high-peak-power SESAM-modelocked thin-disk laser (TDL) based on the gain material Yb-doped lutetia (Yb:Lu2O3), which exceeds a peak-power of 10 MW for the first time. We generate pulses as short as 534 fs with an average power of 90 W and a peak power of 10.1 MW, and in addition a peak power as high as 12.3 MW with 616-fs pulses and 82-W average power. The center lasing wavelength is 1033 nm and the pulse repetition rates are around 10 MHz. We discuss and explain the current limitations with numerical models, which show that the current peak power is limited in soliton modelocking by the interplay of the gain bandwidth and the induced absorption in the SESAM with subsequent thermal lensing effects. We use our numerical model which is validated by the current experimental results to discuss a possible road map to scale the peak power into the 100-MW regime and at the same time reduce the pulse duration further to sub-200 fs. We consider Yb:Lu2O3 as currently the most promising gain material for the combination of high peak power and short pulse duration in the thin-disk-laser geometry.

Hallmarks of Hunds coupling in the Mott insulator Ca2RuO4.

A paradigmatic case of multi-band Mott physics including spin-orbit and Hund's coupling is realized in Ca2RuO4. Progress in understanding the nature of this Mott insulating phase has been impeded by the lack of knowledge about the low-energy electronic structure. Here we provide-using angle-resolved photoemission electron spectroscopy-the band structure of the paramagnetic insulating phase of Ca2RuO4 and show how it features several distinct energy scales. Comparison to a simple analysis of atomic multiplets provides a quantitative estimate of the Hund's coupling J=0.4 eV. Furthermore, the experimental spectra are in good agreement with electronic structure calculations performed with Dynamical Mean-Field Theory. The crystal field stabilization of the dxy orbital due to c-axis contraction is shown to be essential to explain the insulating phase. These results underscore the importance of multi-band physics, Coulomb interaction and Hund's coupling that together generate the Mott insulating state of Ca2RuO4.

Spatially resolved amplitude and phase characterization of femtosecond optical pulses.

Ultrabroadband pulses exhibit a frequency-dependent mode size owing to the wavelength dependence of free-space diffraction. Additionally, rather complex lateral dependence of the temporal pulse shape has been reported for Kerr-lens mode-locked lasers and broadband amplifier chains and in frequency-domain pulse shapers, for example. We demonstrate an ultrashort-pulse characterization technique that reveals lateral pulse-shape variations by spatially resolved amplitude and phase measurements by use of spectral phase interferometry for direct electric-field reconstruction (SPIDER). Unlike with autocorrelation techniques, with SPIDER we can obtain spatially resolved pulse characterization even after the nonlinear process. Thus, with this method the spectral phase of the pulse can be resolved very rapidly along one lateral beam axis in a single measurement.

Collinear type II second-harmonic-generation frequency-resolved optical gating for the characterization of sub-10-fs optical pulses.

For the first time to our knowledge, we demonstrate a collinear frequency-resolved optical gating (FROG) technique that is suitable for the characterization of sub-10-fs pulses. This FROG variant does not suffer from geometrical blurring effects, and a temporal resolution of 1 fs can be achieved without the need for additional aperturing. The apparatus is suitable for subnanojoule pulse energies. We apply this technique for the full characterization of pulses from a Kerr-lens mode-locked Ti:sapphire laser.

Semiconductor saturable-absorber mirror assisted Kerr-lens mode-locked Ti:sapphire laser producing pulses in the two-cycle regime.

Pulses of sub-6-fs duration have been obtained from a Kerr-lens mode-locked Ti:sapphire laser at a repetition rate of 100 MHz and an average power of 300 mW. Fitting an ideal sech(2) to the autocorrelation data yields a 4.8-fs pulse duration, whereas reconstruction of the pulse amplitude profile gives 5.8 fs. The pulse spectrum covers wavelengths from above 950 nm to below 630 nm, extending into the yellow beyond the gain bandwidth of Ti:sapphire. This improvement in bandwidth has been made possible by three key ingredients: carefully designed spectral shaping of the output coupling, better suppression of the dispersion oscillation of the double-chirped mirrors, and a novel broadband semiconductor saturable-absorber mirror.

Characterization of sub-6-fs optical pulses with spectral phase interferometry for direct electric-field reconstruction.

We demonstrate spectral phase interferometry for direct electric-field reconstruction (SPIDER) as a novel method to characterize sub-6-fs pulses with nanojoule pulse energy. SPIDER reconstructs pulse phase and amplitude from a measurement of only two optical spectra by use of a fast noniterative algorithm. SPIDER is well suited to the measurement of ultrabroadband pulses because it is quite insensitive to crystal phase-matching bandwidth and to unknown detector spectral responsivity. Moreover, it combines highly accurate pulse-shape measurement with the potential for online laser system diagnostics at video refresh rates.

Hyperpolarization of the cell membrane of mouse hepatocytes by lactate, pyruvate, and fructose is due to Ca2+-dependent activation of K+ channels and of the Na+/K+-ATPase.

Using superfused mouse liver slices combined with a conventional microelectrode technique, we investigated: (1) the ionic mechanisms involved in the hyperpolarization of the hepatocyte membrane induced by lactate and other gluconeogenic substrates; (2) whether these mechanisms are similar to those underlying the hyperpolarization induced by cell swelling in hypo-osmotic medium; and (3) whether the hyperpolarizing effect of lactate on the hepatocyte membrane is related to gluconeogenesis. Lactate (5 mmol/l) hyperpolarized the hepatocyte membrane after an exposure of 10-20 min, and the hyperpolarization was still present after 70 min. The hyperpolarization induced by lactate, pyruvate (5 mmol/l) and fructose (10 mmol/l), and by exposure to hypo-osmotic medium (250 mosmol/l) was antagonized by ouabain, tetraethylammonium (TEA), and cetiedil (lactate; hypo-osmotic medium). Hyperpolarization induced by lactate was eliminated or attenuated by agents impairing activation of Ca2+-dependent K+ channels, by amiloride, and by a blockade of non-selective cation channels with flufenamic acid and gadolinium. Thapsigargin, increasing cytosolic Ca2+, mimicked lactate's hyperpolarizing effect. Lactate's effect was dependent on extracellular Ca2+. Finally, lactate's hyperpolarizing effect was reduced by inhibiting gluconeogenesis. These findings suggest that metabolism of lactate hyperpolarizes hepatocytes by mechanisms analogous to those underlying the hyperpolarization induced by cell swelling in hypo-osmotic medium. Gluconeogenesis from lactate may cause cell swelling, subsequent activation of Ca2+-dependent K+ channels and of the Na+/K+-ATPase, and thus hyperpolarize the hepatocyte membrane.

Self-starting 6.5-fs pulses from a Ti:sapphire laser.

We demonstrate self-starting 6.5-fs pulses from a Kerr-lens mode-locked Ti:sapphire laser with 200-mW average output power at a pulse repetition rate of ~86 M Hz. This is to our knowledge the shortest pulse ever generated directly from a laser. For dispersion compensation we used a prism pair in combination with double-chirped mirrors, which balances the higher-order dispersion of the prism pair and therefore flattens the average total group-delay dispersion in the laser cavity. For self-starting mode locking we used a broadband semiconductor saturable-absorber mirror.

Hyperpolarization of hepatocytes by 2,5-AM: implications for hepatic control of food intake.

Because 2,5-anhydro-D-mannitol (2,5-AM) seems to stimulate feeding by acting on the liver and because the hepatic membrane potential has been suggested to play an important role in control of feeding ("potentiostatic" hypothesis), we investigated the effect of 2,5-AM on the membrane potential of liver cells with microelectrodes using a superfused liver slice technique. 2,5-AM (2.5 mM), which reduces intracellular ATP in rat liver, hyperpolarized the liver cell membrane in mouse and rat liver slices by 4-7 mV. This hyperpolarization was reversed by quinine (1 mM), an unspecific blocker of Ca2+-dependent K+ channels, and abolished by apamin (20 nM), a blocker of Ca2+-activated K+ channels with low conductance. Amiloride at 10(-3) M, but not at 10(-6) M, or a low-Na medium (26 mM) also eliminated the hyperpolarization. The K+ channel blockers cetiedil (50 microM), glibenclamide (30 microM), and Ba2+ (5 mM); flufenamic acid (100 microM), a blocker of nonselective cation channels; and ouabain (1 mM), an inhibitor of the Na+-K+-adenosinetriphosphatase, did not significantly influence the 2,5-AM-induced hyperpolarization. It is concluded that 2,5-AM hyperpolarizes the liver cell membrane by activating Ca2+-dependent K+ channels. This activation seems to be impaired when the Na+/H+ exchanger is inhibited by amiloride or a low-Na+ medium. The findings also imply that the hyperphagic effect of 2,5-AM observed in rats is not associated with a decrease in the hepatic membrane potential, as postulated by the potentiostatic hypothesis.

Appraisal of a glycopeptide cloaking strategy for a therapeutic oligopeptide: glycopeptide analogs of the renin inhibitor ditekiren.

Among the limitations to the practical therapeutic oligopeptide are low oral availability, indifferent aqueous solubility, and an astonishing efficient sequestration and biliary elimination by a multi-capacity liver transporter. Given the purposed use of N- and O- linked saccharides as functional appendages of eukaryotic peptides and proteins, a strategy of glycopeptide mimicry was examined for the oligopeptide renin inhibitor, ditekiren. The anticipation was that the saccharide would impart significant aqueous solubility, and might impact beneficially on the remaining two limitations. Execution of this approach was achieved by the removal of the (dimethylethoxy)carbonyl amino terminus of ditekiren, and its substitution by Boc-L-asparagine N-linked mono- and disaccharides. Potent hypotensive activity, as measured by a human renin-infused rat assay, is observed for virtually all of these structures (N-linked beta-pyranose D-N-acetyglucosaminyl, D-glucosaminyl, D-N-acetylgalactosaminyl, D-mannosyl, D-galactosyl, D-maltosyl, D-cellobiosyl, D-chitobiosyl, but not L-fucosyl). The basis for this dramatic improvement (relative to ditekiren in the same assay) is the diversion of the peptide clearance from rapid liver biliary clearance to slower urinary clearance (Fisher, J. F.; Harrison, A. W.; Wilkinson, K. F.; Rush, B. R.; Ruwart, M. J. J. Med. Chem. 1991, 34, 3140). Guided by the human renin-infused rat hypertension assay, an evaluation of the linker-saccharide pairing was made. Loss of hypotensive activity is observed upon substitution of the Boc-L-asn by Boc-D-asn, and by removal of the Boc amino terminus of the glycopeptide. Potent hypotensive activity is preserved by replacement of the Boc-L-asn linker by succinate, malate, tartrate, and adipate linkers. With the longer adipate spacer, attachment of the saccharide to the P-3 phenylalanine--with omission of the P-4 proline--retains activity. These data suggest value to the glycopeptide guise for preserving the in vivo activity, and for the beneficial manipulation of pharmacodynamics, of this renin inhibitory oligopeptide. This strategy may have general applicability.

Purification of an endogenous digitalislike factor from human plasma for structural analysis.

In previous reports, we described the isolation and characterization of an endogenous digitalislike factor (EDLF). In this report, we describe a unique combination of bioassay and large-scale purification methodology that made possible the purification of sufficient quantities of this inhibitor of Na+,K(+)-ATPase for structural analysis. Using an initial XAD-2 extraction and preparative high-performance liquid chromatography followed by a batch enzyme affinity extraction and two subsequent semipreparative chromatographic steps, 300 l of human plasma was processed, yielding 31 micrograms (53 nmol) of pure EDLF and representing purification on a dry weight basis in excess of 0.6 billionfold. Four divergent pieces of evidence, including chromatographic, mass spectrometric, immunoreactive, and binding characteristics, suggested that the EDLF purified in the present study was either ouabain or an isomer of ouabain. This material may represent a plasma-borne, naturally occurring, selective, high-affinity ligand for the digitalis binding site that may play a significant role in the modulation of the sodium pump and thereby cellular electrolyte homeostasis in humans.

A monoclonal antibody to exfoliated surface vesicles that recognizes a membrane-associated erythroid burst-promoting activity.

A monoclonal antibody (MoAb) recognizing a membrane-associated erythroid burst-promoting factor was prepared by immunizing BALB/c mice with plasma membrane-derived vesicles exfoliated from lymphocytes under serum-free conditions. Hybrids secreting antibody reactive with lymphocyte plasma membranes were formally cloned and IgG was purified from monoclonal supernatants or from BALB/c mouse ascites fluid. Two clones (D3-E4 and D3-G9) were found to suppress burst forming unit-erythroid (BFU-E) proliferation when added directly to serum-free human marrow culture. Inhibition to a level of 100% was observed in a dose-dependent fashion over a wide range of antibody concentrations (0-200 micrograms/mL). Neither antibody altered the proliferation of colony forming unit-granulocyte macrophage (CFU-GM) or colony forming unit-granulocyte-erythroid-monocyte-megakaryocyte (CFU-GEMM) progenitor cells in human bone marrow culture. The D3-E4 clone was found to produce an IgG1 antibody which adsorbs an erythroid burst-promoting activity (BPA) from supernatants of, and octylglucoside extracts of shed vesicles present in, serum-free, lymphocyte conditioned medium (LCM), and which recognizes a vesicular protein of Mr approximate 30,000 on immunoblots of membrane proteins electrophoresed on sodium dodecyl sulfate (SDS)/polyacrylamide and transferred to nitrocellulose. In contrast, the D3-G9 clone was found to produce an IgG1 cytotoxic antibody. These antibodies will be important to the study of cell-cell and growth factor-cell interactions in vitro.

Quantitative assay of capsaicin-sensitive thiamine monophosphatase and beta-glycerophosphatase activity in rodent spinal cord.

The axon terminals of some capsaicin-sensitive sensory neurons in the spinal cord of the rat contain high amounts of acid phosphatase (EC 3.1.3.1) activity. We quantitated this activity in control and capsaicin-treated rats and mice in a biochemical assay using beta-glycerophosphate (beta-GP) and thiamine monophosphate (TMP), which have both been used in previous histological investigations, as substrates and measured the amount of phosphate liberated from particular fractions. The ventral spinal cord of rats yielded 209 +/- 9 (mean +/- S.E.M.) nmol phosphate/mg protein/h from beta-GP and 18 +/- 5 nmol from TMP; the values for the upper dorsal horn are 544 +/- 42 and 198 +/- 12 for beta-GP and TMP respectively. Values for mouse spinal cord tissue are quite similar; the spinal cord of guinea pigs contains lower amounts of beta-GPase and very little TMPase activity per mg protein. There was a fairly broad pH optimum between 5.4 and 6.3. After capsaicin (50 mg/kg s.c.) pretreatment, beta-GPase activity in the upper dorsal horn was decreased by 29% in rats and by 17% in mice; TMPase activity was reduced by 48% and 37% respectively. Values in the ventral spinal cord were unchanged. It is proposed that biochemical measurement of TMPase activity might be useful in quantitative investigations of acid phosphatase activity (e.g. "FRAP") in capsaicin-sensitive sensory neurons.

Purification and characterization of rabbit ocular mucin.

Ocular mucin, the major product of conjunctival goblet cells, constitutes the innermost layer of preocular tear film. Ocular mucin is known for its limited amount and inaccessibility. Using impression cytology, mucus strands collected from the inferior fornix of either rabbit or human eyes were found to contain inflammatory cellular debris. In order to circumvent these difficulties and to isolate native mucin molecule(s), we bathed rabbit eyes in fluid containing isotonic PBS and 5.5 X 10(-4) M acetylcholine for 4 or 12 hr. Bathing fluids containing rabbit ocular mucin (ROM), 1 ml per eye, were pooled and combined with 1M guanidine HCl and protease inhibitors containing EDTA, PMSF, and sodium azide to avoid any possible enzymatic degradation, and then separated under the same conditions by Sepharose CL-4B. In parallel, commercial porcine stomach mucin (PSM) was purified and used to compare with ROM. We also developed nitrocellulose-based dot semi-quantitative assays for nucleic acid, protein, and glycoprotein. PAS-positive fractions monitored by such a dot assay were collected at CL-4B void volume and then separated from nucleic acid contaminants by CsCl-gradient ultracentrifugation. A protein fraction, 65K, poorly-glycosylated, with high contents of Asx, Glx, and Gly was found strongly associated with both ROM and PSM, and was only separable by ultracentrifugation in 4M guanidine HCl and CsCl. Purification of the ROM was verified by SDS-polyacrylamide gel electrophoresis, amino acid analysis, and carbohydrate analysis. These results will allow future exploration of the molecular mechanism by which tear film is achieved.

Modulation of the contractile activity of the guinea-pig lung parenchymal strip by exogenous 5,8,11,14,17-eicosapentaenoic acid.

Exogenous eicosapentaenoic acid (EPA, 16.5 mumol/l or 33 mumol/l) inhibited dose-dependently the anaphylactic contractile response of guinea-pig lung parenchymal strips suspended in an organ bath. As determined by radioimmunoassay, EPA inhibited in a dose-dependent manner the anaphylactic release of the cyclooxygenase products thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha but simultaneously enhanced the release of sulfidopeptide (SP)-leukotrienes (LT). Indomethacin (2.8 mumol/l) abolished the release of cyclooxygenase products but potentiated the release of SP-LT. However, indomethacin treatment did not affect the inhibitory action of EPA on the contractile response of the anaphylactic lung strips. The lipoxygenase inhibitor, esculetin (50 mumol/l), inhibited the release of SP-LT and also that of cyclooxygenase products of polyunsaturated fatty acid metabolism. The combination of esculetin and EPA resulted in enhanced inhibition of the anaphylactic contractile response as compared to EPA alone. By reversed phase high pressure liquid chromatography (HPLC), SP-LT from anaphylactic lung parenchymal strips was shown to consist of LTD4 and LTE4. EPA-pretreated lung strips released upon immunologic challenge additional immunoreactivity comigrating with authentic LTC4, LTC5, LTD5 and LTE5. While anaphylactic control strips also released LTB4, in the bath fluid of EPA-treated strips, an additional immunoreactive compound migrating with the retention time of LTB5 was observed. In non-sensitized guinea-pig lung parenchymal strips EPA inhibited the myotropic activity of exogenous mediators such as histamine (9 mumol/l), LTC4 (16 nmol/l) and the TX mimetic U 46619 (28.4 nmol/l), an effect which was neither affected by indomethacin (2.8 mumol/l) nor by the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)