Collapse of superconductivity in cuprates via ultrafast quenching of phase coherence.

The possibility of driving phase transitions in low-density condensates through the loss of phase coherence alone has far-reaching implications for the study of quantum phases of matter. This has inspired the development of tools to control and explore the collective properties of condensate phases via phase fluctuations. Electrically gated oxide interfaces1,2, ultracold Fermi atoms3,4 and cuprate superconductors5,6, which are characterized by an intrinsically small phase stiffness, are paradigmatic examples where these tools are having a dramatic impact. Here we use light pulses shorter than the internal thermalization time to drive and probe the phase fragility of the Bi2Sr2CaCu2O8+δ cuprate superconductor, completely melting the superconducting condensate without affecting the pairing strength. The resulting ultrafast dynamics of phase fluctuations and charge excitations are captured and disentangled by time-resolved photoemission spectroscopy. This work demonstrates the dominant role of phase coherence in the superconductor-to-normal state phase transition and offers a benchmark for non-equilibrium spectroscopic investigations of the cuprate phase diagram.

Influence of Spin-Orbit Coupling in Iron-Based Superconductors.

We report on the influence of spin-orbit coupling (SOC) in Fe-based superconductors via application of circularly polarized spin and angle-resolved photoemission spectroscopy. We combine this technique in representative members of both the Fe-pnictides (LiFeAs) and Fe-chalcogenides (FeSe) with tight-binding calculations to establish an ubiquitous modification of the electronic structure in these materials imbued by SOC. At low energy, the influence of SOC is found to be concentrated on the hole pockets, where the largest superconducting gaps are typically found. This effect varies substantively with the k_{z} dispersion, and in FeSe we find SOC to be comparable to the energy scale of orbital order. These results contest descriptions of superconductivity in these materials in terms of pure spin-singlet eigenstates, raising questions regarding the possible pairing mechanisms and role of SOC therein.

Electronic stripe patterns near the fermi level of tetragonal Fe(Se,S).

FeSe1-xSx remains one of the most enigmatic systems of Fe-based superconductors. While much is known about the orthorhombic parent compound, FeSe, the tetragonal samples, FeSe1-xSx with x > 0.17, remain relatively unexplored. Here, we provide an in-depth investigation of the electronic states of tetragonal FeSe0.81S0.19, using scanning tunneling microscopy and spectroscopy (STM/S) measurements, supported by angle-resolved photoemission spectroscopy (ARPES) and theoretical modeling. We analyze modulations of the local density of states (LDOS) near and away from Fe vacancy defects separately and identify quasiparticle interference (QPI) signals originating from multiple regions of the Brillouin zone, including the bands at the zone corners. We also observe that QPI signals coexist with a much stronger LDOS modulation for states near the Fermi level whose period is independent of energy. Our measurements further reveal that this strong pattern appears in the STS measurements as short range stripe patterns that are locally two-fold symmetric. Since these stripe patterns coexist with four-fold symmetric QPI around Fe-vacancies, the origin of their local two-fold symmetry must be distinct from that of nematic states in orthorhombic samples. We explore several aspects related to the stripes, such as the role of S and Fe-vacancy defects, and whether they can be explained by QPI. We consider the possibility that the observed stripe patterns may represent incipient charge order correlations, similar to those observed in the cuprates.

Direct determination of mode-projected electron-phonon coupling in the time domain.

Ultrafast spectroscopies have become an important tool for elucidating the microscopic description and dynamical properties of quantum materials. In particular, by tracking the dynamics of nonthermal electrons, a material's dominant scattering processes can be revealed. Here, we present a method for extracting the electron-phonon coupling strength in the time domain, using time- and angle-resolved photoemission spectroscopy (TR-ARPES). This method is demonstrated in graphite, where we investigate the dynamics of photoinjected electrons at the [Formula: see text] point, detecting quantized energy-loss processes that correspond to the emission of strongly coupled optical phonons. We show that the observed characteristic time scale for spectral weight transfer mediated by phonon-scattering processes allows for the direct quantitative extraction of electron-phonon matrix elements for specific modes.

Characterization of prostaglandin E2 binding to isolated human adipocytes.

Prostaglandin (PG) E2 binding to fat cells and its consequent antilipolytic effect have been studied in experiments using laboratory animals, but no binding studies have yet been reported using adipocytes from humans. Consequently, we have characterized PGE2 binding to human isolated fat cells to compare the apparent binding constant to the IC50 for the antilipolytic effect of PGE2. Our data indicate that human fat cells contain binding sites that specifically recognize prostaglandins of the E series and demonstrate stereospecific recognition of the more potent of two 15-methyl-PGE2 analogues. There was no evidence for rapid metabolism of PGE2 by isolated adipocytes such as occurs in lung and liver tissue. A double-reciprocal plot of binding data obtained at saturation using [3H]PGE2 and increasing concentrations of PGE2 indicated a single class of binding sites with an apparent binding constant (0.54 nM) that agreed well with the IC50 (0.26 nM) for the antilipolytic effect of PGE2 we observed in human fat cells. The findings from these binding and lipolysis studies are in general agreement with published observations using adipocytes from rodents and provide evidence that the conclusions reached from previous studies of laboratory animals are relevant to adipocyte physiology in humans.

Prostaglandin E2 metabolite levels during diabetic ketoacidosis.

Insulin therapy was withdrawn from 15 well-controlled type I diabetic subjects for no longer than 18 h to examine the sequence with which 13,14-dihydro-15-keto-PGE2 (PGE-m), glucagon, norepinephrine, and epinephrine increased in circulating blood in diabetic subjects becoming ketoacidotic. Fourteen of 15 patients had increments in PGE-m; 12/12, 12/15, and 13/15 had increments in glucagon, norepinephrine, and epinephrine, respectively. Six of the 15 patients developed mild diabetic ketoacidosis (DKA) by 12-18 h; all had nonmeasurable C-peptide levels. This DKA group had significantly greater increments of PGE-m (835 +/- 130 versus 276 +/- 111 pg/ml, mean +/- SEM, P less than 0.01) but not glucagon, norepinephrine, or epinephrine compared with the 9 non-DKA patients. In the DKA group, there were significant PGE-m and glucagon increments in the circulation by 3 h, significant norepinephrine increments by 9 h, and epinephrine increments in 5/6 patients by 12 h (not statistically significant) of insulin withdrawal. These studies document that (1) PGE-m accumulates in the circulation during DKA, (2) PGE-m and glucagon increase before catecholamines, and (3) PGE-m, glucagon, and catecholamine levels promptly return to normal levels when insulin therapy is reinstituted. It is suggested that elevated PGE-m levels early in the onset of DKA may represent a host-defense mechanism.

Renin activity in dog brain: enzymological similarity to cathepsin D.

The distribution and biochemical properties of the renin activity present in the dog brain were compared with those of the lysosomal enzyme cathepsin D. Renin and cathepsin activity were present in all brain regions studied, in association with high angiotensinase activity. Brain renin activity was partially purified by ammonium sulfate fractionation and Sephadex gel filtration, resulting in the removal of angiotensinase activity. The specific brain renin activity increased approximately one hundred times during this procedure; cathepsin D activity accompanied the brain renin activity throughout the purification and showed a similar increase in specific activity. The renin and cathepsin activity in the partially purified preparation behaved identically during isoelectric focusing. The partially purified renin and cathepsin activity exhibited saturation kinetics with their respective substrates and were without activity above pH 6.0. Both enzyme activities were irreversibly inhibited by the pepsin inhibitor pepstatin, in nanomolar concentrations. These data, in conjunction with the literature concerning brain cathepsin, suggest that the renin activity in brain is due to cathepsin D, and that this renin activity exhibited by cathepsin D may be of limited significance under physiological conditions.

Biochemical properties of big renin extracted from human plasma.

The properties of big renin, a relatively inactive form of renin isolated from human plasma, were examined following partial purification by gel filtration. Exposure of big renin to pH 3.0-3.6, or brief incubation with trypsin or pepsin, resulted in a ten-fold increase in enzymatic activity. Activation was not effected by 4M NaCl, 6M urea, or incubation with neuraminidase. Both before and after inactivation, big renin eluted from Sephadex gel more rapidly than normal plasma renin. During polyacrylamide gel disc electrophoresis, inactive big renin migrated more slowly than either normal renin or big renin previously activated. Using sheep substrate, the enzyme kinetics of normal renin and previously activated big renin were identical, while inactive big renin possessed a higher Michaelis constant. These data indicate that big renin is closely related biochemically to normal plasma renin. As the activation of big renin results in the formation of the substance even more similar to normal renin, the possibility exists that big renin may prove to be a precursor form of normal renin.

Occurrence of big renin in human plasma, amniotic fluid and kidney extracts.

Big renin, a relatively inactive renin which possesses a molecular weight larger than that of normal plasma or renal renin, has been demonstrated by gel filtration in certain human plasma, tumor extracts, and amniotic fluid. Big renin was not present in normal plasma or kidney extracts. Plasma from 3 hypertensive patients with nephropathy contained chiefly big renin. Varying proportions of both big and normal renin activity were present in plasma of other patients with hypertension and proteinuria. The renin present in amniotic fluid, which increased in activity following exposure to acid pH, was shown to be big renin in two patients. Large amounts of circulating big renin apparently can cause hypertension in patients with Wilms' tumors. Furthermore, the relatively inactive big renin may replace normal plasma renin in some patients, resulting in low plasma renin activity.

A monoclonal antibody specific for the amino terminal sequence of human prorenin identifies a common epitope on renal and amniotic fluid inactive renins.

A synthetic nonapeptide corresponding to the predicted amino terminus of human prorenin was synthesized and used as an antigen in the production of mouse hybridomas. Forty-seven clones producing antibody to this peptide were identified and screened for ability to bind to partially purified amniotic fluid inactive renin in a soluble phase assay. None showed activity. One purified antibody, 4D3-3C4, was found to bind by Western blotting to renal and amniotic fluid inactive renins, molecular size 52 kDa, after gel electrophoresis in sodium dodecyl sulphate (SDS) following reduction with mercaptoethanol. In contrast, the anti-renin monoclonal antibody, R3-27-6, recognizes active renin, molecular size 38 kDa, and two inactive renin species, 42 kDa and 52 kDa, in the same renin preparations. Kidney and amniotic fluid apparently contain an inactive renin that possesses the complete prorenin sequence. These data indicate that high molecular weight inactive renin from both kidney and amniotic fluid contain an epitope, accessible to antibody only after denaturation, which represents the amino-terminal octapeptide sequence of prorenin. The inactive renin preparations tested also contain smaller fragments which either possess this epitope or do not, while still reacting with antibodies to active renin. It is likely that all these smaller inactive renin species are the result of proteolysis, either post-synthetic or in vitro.

Ocular renin-angiotensin: immunohistochemical evidence for the presence of prorenin in eye tissue.

Angiotensin II (A2) is a vasoconstrictor generated by the renin-angiotensin system. A2 appears to act also as an angiogenic factor. Recent evidence suggests that renin is synthesized at many tissue sites and may generate A2 locally. Local A2 may have important functions in the normal and diseased eye. We examined eight human eyes by immunostaining with an antibody to prorenin, the biosynthetic precursor of renin. In all eyes, prorenin staining was extensive in the pars plicata of the ciliary body suggesting that the ciliary body synthesizes renin and this renin may be part of an ocular A2 generating system.

Big renin: identification, chemical properties and clinical implications.

Big renin has a greater molecular weight (63,000 versus 43,000) than normal renin, but it shares the characteristic enzymatic and immunologic properties of normal renin. As it exists in the kidney or plasma of a patient, big renin is less active than normal renin, but its enzymatic activity is greatly enhanced by exposure to pH values of 3.0 to 3.6 or by brief incubation with pepsin or trypsin. Use of the terms prorenin and zymogen might be withheld until big renin is shown to exist in normal tissue or plasma and to be converted to normal renin in vivo. To date, big renin has been found in renal tumors and other abnormal kidney tissues as well as in the plasma of patients with renal disorders. The remarkable activation of big renin at pH levels of 3.3 can be used to detect its presence. If a method involving acidification is used to quantitate plasma renin activity of a patient with circulating big renin, the activated plasma renin activity greatly exceeds that measured in plasma maintained at neutral pH. Gel filtration of plasma is used to prove the presence of big renin. When large amounts of big renin are secreted by a renal tumor, hyperfusion may ensue and be cured by removal of the tumor. The secretion of small amounts of big renin does not necessarily result in any physiologic disorder. However, if there is a concomitant diminution or absence of normal renin a state of apparent hyporeninemia exists, as we have observed in diabetic nephropathy; this may be associated with hypoaldosteronism and hyperkalemia. Big renin does not appear to respond to physiologic changes that stimulate or suppress normal plasma renin activity. The finding of big renin may indicate the presence of certain renin-secreting renal tumors or other renal disorders, especially diabetic nephropathy.

A preliminary evaluation of an innovative synthetic soft tissue simulation module ('Skilltray') for use in basic surgical skills workshops.

The results of a preliminary evaluation comparing the relative merits of biological (freshly-prepared animal offal tissue) and synthetic (Skilltray) simulation modalities are presented, subsequent to their use during two basic surgical skills courses organised by The Royal College of Surgeons of England and The Royal College of Physicians and Surgeons of Glasgow in September 1995, and at which 18 SHO grade surgical trainees attended. Each trainee completed a questionnaire at the end of the first session on the second day of the course to assist the evaluation. Our conclusions were as follows: 1. The synthetic tissues evaluated provided a useful and functionally reproducible means for learning the basic exercises included in the mandatory skills course. 2. Freshly-prepared animal tissues undoubtedly provided a more "realistic' medium for rehearsing the basic surgical techniques taught. Trainees preferred to use the synthetic tissues initially and then to progress to the fresh equivalents subsequently. 3. The Skilltray provided all the requisite elements for rehearsing basic tissue handling, suturing, and anastomotic techniques in a self-contained, easily transportable module. We would suggest that such a unit be given to each participant to take away at the end of the basic skills course, to enable consolidation of the skills learned. 4. Where the use of fresh tissues is not possible the highly functional nature of the synthetic simulators evaluated make it acceptable then to use them as the only training modality.

Properties of inactive renin in human plasma.

1. "Inactive" renin in human plasma can be revealed by pH 3.3- or cold-mediated activation and in normal plasma represented 76% of the "total" renin. 2. Pregnancy plasma contained considerably more "inactive" renin and consisted of 93% of "total" renin. 3. "Active" renin in normal plasma had an apparent molecular weight of 43,000 compared with 60,000 for "active" renin in pregnancy plasma by gel filtration. 4. "Inactive" renin in pregnancy plasma also had an apparent molecular weight of 60,000, while in normal plasma there were two peaks of inactive renin at 62,000 and 46,000. 5. After affinity chromatography of a protein preparation from pregnancy plasma on Concanavalin A-Sepharose activation by pH 3.3 could no longer be produced, suggesting that the activating factor had been removed, as would occur if it were not a glycoprotein. When pepsinogen, in a concentration similar to that found in plasma, was added prior to dialysis to pH 3.3 activation was restored. 6. Ion-exchange chromatography demonstrated that at pH 8.4 "inactive" renin bore slightly less negative charges than "active" renin. 7. "Inactive" renin in human plasma therefore appears to be a larger molecular weight species than the "active" renin in normal plasma and is capable of activation during treatment to pH 3.3 or cold with no apparent alteration in size. The results suggest an important role of pepsin (after conversion from pepsinogen) in the activation of "inactive" renin during dialysis at pH 3.3.

Basophil-sensitizing antibody response to herpes simplex viruses in rabbits.

Antibodies to herpes simplex virus type 1 and type 2 were detected in the sera of rabbits by release of histamine from basophils sensitized in vitro with the sera. The time course of the appearance of the antibodies, the dose-response curve of the release of histamine in relation to antigen concentration, the sedimentation characteristics of the antibodies in sucrose gradients, and the ability to destroy the sensitizing capacity of the sera with heat suggest that the antibodies being assessed were of the IgE class. These antibodies were induced in animals injected intradermally, intramuscularly, and i.p. with live virus. The antibodies were detected 1 week after primary injection and a similar time course of antibody appearance was observed after a second or third injection. The same cross-reactivity between type 1 and type 2 virus observed with IgG antibody was also observed with IgE antibody.

Presence of thymic antigen on rabbit basophils.

A goat heteroantiserum specific for a rabbit thymus lymphocyte antigen (RTLA) reacted with rabbit basophils resulting in the release of histamine. This activity was equally absorbed out by thymocytes or basophils. Absorption with either of these cell types also resulted in equal loss of thymocytotoxicity. No effect in either system occurred after absorption with either granulocytes or rabbit fibroblasts. These results could not be explained by the presence of immune complexes or aggregated globulin present in the RTLA antiserum. Further, the RTLA anti-serum had no anti-IgE activity, as demonstrated by its lack of reactivity with mast cells that were otherwise capable of releasing histamine normally after challenge with antigen. We have thus shown a basic difference between mast cells and basophils. We conclude that the rabbit basophil may bear a thymic marker.

Evaluation of resident performance in an outpatient internal medicine clinic using standardized patients.

OBJECTIVE: To observe and evaluate the performance of primary care internal medicine residents within the outpatient clinic milieu. DESIGN: Longitudinal descriptive study. PATIENTS/PARTICIPANTS: 48 internal medicine resident encounters with two standardized patients at the University of Wisconsin General Internal Medicine Clinics. INTERVENTION: Residents were rated by the standardized patients with a medical skills checklist and an interpersonal skills checklist, and by the staffing physician with a clinical reasoning skills checklist. The investigators reviewed audiotapes of the standardized patient encounters for strategic management skills. MAIN RESULTS: Resident performance on these scales was examined for improvement with years of training; when considered separately, no such effect was seen for either standardized patient case. When the cases were grouped together, however, there was significant improvement on the Clinical Reasoning Instrument. The grouped standardized patient data were compared with data from inpatient faculty evaluations of the residents. Faculty evaluations correlated with standardized patient evaluations of resident performance only on the medical checklist. Finally, comparison of the four assessment scales demonstrated a significant correlation between interpersonal skills, as assessed by the patient, and strategic management skills. CONCLUSION: Resident outpatient performance, measured in a blinded setting, does not improve with year of training. Faculty inpatient assessments of residents correlate with medical "thoroughness" as measured by a medical skills checklist, and interpersonal skills as rated by standardized patients correlate with resident use of strategic medical management.

Skin simulation for minor surgical procedures.

A simulated skin preparation is described which is made by bonding siliconized rubber to a latex foam base. This composite material, which simulates both the dermis/epidermis and subcutaneous fat, provides a realistic model which can be used to teach excision of skin lesions and a variety of suturing methods. We believe that this simulator is of value not only for surgeons in-training but also will allow general practitioners to improve their technical skills in performing minor surgical procedures.