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.

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.

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.

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.

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.

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.

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.

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.

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)

Differential responding to the beta movement after waking from REM and nonREM sleep.

Ten young adults were wakened from REM sleep and from nonREM sleep on two nonconsecutive nights and were tested to determine their upper and lower beta-movement thresholds. The ranges of the illusion were found to be significantly wider after waking from REM sleep than after waking from nonREM sleep or before sleep. The differential responding to the beta movement supports the experimental hypothesis that apparent motion may provide sensitive detectors of the operation during wakefulness of the Basic Rest-Activity Cycle, of which REM and nonREM sleep are opposite phases that carry over into wakefulness.

Methylation of integrated viral DNA sequences in hamster cells transformed by adenovirus 12.

Data have been presented which demonstrate that the Ad12 DNA sequences integrated into the DNA of four lines of Ad12-transformed hamster cells are extensively methylated. Methylation in mammalian-cell DNA presumably occurs at 5'-CCGG-3' sequences mainly at the internal C residue. The majority, though not all, of the 5'-CCGG-3' sequences present in integrated Ad12 DNA are methylated. Further experiments will be required to elucidate the functional significance of the methylation of integrated Ad12 DNA. Ad12 DNA isolated from purified virions is not methylated to any significant extent. Recent results indicate that segments of the integrated viral DNA, which are expressed into mRNA in transformed cells, are undermethylated, whereas segments that are not expressed are extensively methylated.

Methylation of integrated adenovirus type 12 DNA sequences in transformed cells is inversely correlated with viral gene expression.

The adenovirus type 12 (Ad12) DNA sequences integrated into the DNA of four lines of Ad12-transformed hamster cells are extensively methylated. Methylation in mammalian cell DNA is believed to occur predominantly at 5'-C-G-3' sequences. The majority, although not all, of the 5'-C-C-G-G-3' sequences present in integrated Ad12 DNA are methylated. Ad12 DNA isolated from purified virions, on the other hand, is not methylated to any significant extent. The segments of the integrated viral DNA comprising early genes, which are expressed as mRNA in two lines of Ad2-transformed hamster cells, are undermethylated in comparison to late viral segments, which are not expressed and are extensively methylated. In contrast, in two lines of Ad12-induced rat brain tumor cells, some of the late viral genes have been shown to be expressed as mRNA. The segment of the integrated Ad12 DNA that comprises these late genes, the EcoRI B fragment, is undermethylated in comparison to the extensive methylation of the same fragment in Ad12-transformed hamster cells. Thus, there appears to exist a striking inverse correlation between the levels of methylation of specific DNA segments and the extent to which these segments are expressed as mRNA. The functional significance of this correlation remains to be determined. It may provide a clue to understanding the regulation of gene expression in transformed cells and perhaps in eukaryotic cells in general.

L-triiodothyronine augments erythropoietic growth factor release from peripheral blood and bone marrow leukocytes.

To investigate cellular mechanisms involved in thyroid hormone stimulation of erythropoiesis, we studied the response of erythroid burst-forming unit (BFU-E) proliferation to L-triiodothyronine (L-T3) in a serum-free culture system. When added directly to culture, L-T3 stimulates erythroid burst formation by normal human bone marrow cells. In contrast, granulocyte-macrophage colony formation is unaffected. Enhancement of erythroid burst formation by L-T3 required the presence of nylon wool adherent and/or B-4 antigen-positive light-density marrow populations. Addition of other erythropoietic factors including platelet-derived growth factor and insulinlike growth factor II did not abrogate this apparent cellular requirement. Pulse exposure of marrow and peripheral blood mononuclear cells (greater than 95% lymphocytes) to L-T3 accelerates the release of a soluble factor that augments BFU-E proliferation into serum-free liquid culture medium. Time-course studies show that this factor appears in conditioned medium (CM) coincidentally with erythroid burst-promoting activity (BPA). Furthermore, incubation of CM with an antibody known to react with and adsorb BPA from solution removes the inducible mitogen. Biochemical analysis of CM prepared from unexposed and L-T3 pulse-exposed cells indicates that the rate of protein appearance is accelerated by L-T3 in a fashion that immediately precedes growth factor release and that several polypeptides are quantitatively increased. We conclude that unlike erythropoietin, which is mitogenic for progenitor cells directly, L-T3 enhances BFU-E proliferation indirectly by augmenting the release of soluble BPA-like molecules from accessory cells in culture.

Patterns of integration of viral DNA sequences in the genomes of adenovirus type 12-transformed hamster cells.

The patterns of integration of the viral genome have been analyzed in four hamster cell lines transformed by adenovirus type 12 (Ad12). It has previously been shown that in each of the cell lines HA12/7, T637, A2497-2 and A2497-3, the viral genome persists in multiple copies, and that different parts of the viral DNA are represented non-stoichiometrically (Fanning and Doerfler, 1976). All four cell lines are oncogenic when injected into hamsters. The DNA from each of the cell lines was extracted and cleaved in different experiments with restriction endonucleases Bam HI, Bgl II, Eco RI, Hind III, Hpa II or Sma I. The DNA fragments were separated on 1% agarose slab gels and transferred to nitrocellulose filters by the Southern technique. Ad12 DNA sequences were detected by hybridization to Ad12 DNA, which was 32 P-labeled by nick translation, and by subsequent autoradiography. In some experiments, the 32P-labeled Eco RI restriction endonuclease fragments of Ad12 DNA were used to investigate the distribution of specific segments of the viral genome in the cellular DNA. For each cell line, a distinct and specific pattern of integrated viral DNA sequences is observed for each of the restriction endonucleases used. Moreover, viral sequences complementary to the isolated Eco RI restriction endonuclease fragments are also distributed in patterns specific for each cell line. There are striking differences in integration patterns among the four different lines; there are also similarities. Because the organization of cellular genes in virus-transformed as compared to normal cells has not yet been determined, conclusions about the existence or absence of specific integration sites for adenovirus DNA appear premature. Analysis of the integration patterns of Ad12 DNA in the four hamster lines investigated reveals that some of the viral DNA molecules are fragmented prior to or during integration. Analysis with specific restriction endonuclease fragments demonstrates that the Eco RI B, D and E fragments, comprising a contiguous segment from 0.17-0.62 fractional length units of the viral DNA, remain intact during integration in a portion of the viral DNA molecules. Although each cell line carries multiple copies of Ad12 DNA, the viral DNA sequences are concentrated in a small number of distinct size classes of fragments. This finding is compatible with, but does not prove, the notion that at least a portion of the viral DNA sequences, is integrated into repetitive sequences, or else that the integrated viral sequences have been amplified after integration. In the three cell lines which were tested, the integration pattern is stable over many generations, with continuous passage-twice weekly-of cells for 6-7 months. In the three cell lines which were examined, the integration pattern is identical in a number of randomly isolated clones. Hence it can be concluded that the patterns of integration are identical among all cells in a population of a given line of transformed cells.

Isolation of a highly pure archeocyte fraction from the fresh-water spongeEphydatia fluviatilis.

A pure archeocyte fraction was isolated from the fresh-water spongeEphydatia fluviatilis by density gradient centrifugation of dissociated cell suspensions. The nature and purity of the fraction were confirmed by electron microscopy.

Morphological revertants of adenovirus type 12-transformed hamster cells.

Morphological revertants have been isolated from one line of adenovirus type 12-transformed hamster cells. This line, T637, is oncogenic in hamsters and contains multiple copies of the virus genome per cell. Different parts of the virus genome are represented in non-stoichiometric amounts and the virus DNA persists in the cells in an integrated form. The pattern of integrated virus genomes has been determined by the blotting technique. In the T637 line, morphological revertants arise spontaneously at relatively high frequency. Two of these revertants have been cloned. In contrast to the T637 line, the revertants F10 and G12 exhibit fibroblastic morphology. The patterns of integrated virus genomes in the revertants differs markedly from that of the T637 line; one of the revertant cell lines, F10, appears to have lost all virus DNA sequences. The morphological revertants continue to express the oncogenic phenotype, although the time required to produce tumours in animals appears to be prolonged compared to the parental BHK21 and the T637 cell lines. A number of biological parameters of the revertant lines have also been investigated.

Aggregative properties of different cell types of the fresh-water spongeEphydatia fluviatilis isolated on ficoll gradients.

Cell suspensions of the fresh-watersponge Ephydatia fluviatilis have been fractionated by means ofFicoll gradient centrifugation. Three fractions were isolated. The densest contains archeocyte-like cells only; the intermediate fraction is very rich in choanocytes, and the lightest is a mixture of cell types. Earch fraction shows specificaggregative properties and potentialities to reconstitute functional sponges.It appears that the sequence of reconstitution events can be selectively altered by certain disequilibria in the cell populationThese preliminary results constitute a first approach to the analysis ofcell type specificity in sponges.