High-energy scale revival and giant kink in the dispersion of a cuprate superconductor

In the present photoemission study of a cuprate superconductor Bi1.74Pb0.38Sr1.88CuO6+delta, we discovered a large scale dispersion of the lowest band, which unexpectedly follows the band structure calculation very well. The incoherent nature of the spectra suggests that the hopping-dominated dispersion occurs possibly with the assistance of local spin correlations. A giant kink in the dispersion is observed, and the complete self-energy containing all interaction information is extracted for a doped cuprate in the low energy region. These results recovered significant missing pieces in our current understanding of the electronic structure of cuprates.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Lett. on May 21, 200

Effect of helium ion irradiation on pure W, W-5Ta and W-5Re: a micro-tensile and nanoindentation investigation of mechanical properties

Micro-tensile testing has been used to study the response of pure tungsten and two tungsten alloys to helium ion irradiation. Commercially supplied plates of W, W-5Ta and W-5Re were irradiated using 6 MeV helium ions at room temperature. The ion energy was attenuated with an energy spreading device such that a uniform level of damage at 0.6 dpa (and 11,000 appm He) was deposited at the 3–9 µm depth. Focused ion beam milling was used to fabricate dog-bone shaped, micro-tensile samples 5 × 5 µm in cross-sectional area and 17 µm in length from the unirradiated and irradiated samples. All micro-tensile samples were tested at a quasi-static strain rate and the stress–strain curves were analysed to determine the mechanical properties. A close correlation was found between micro-tensile results and the bulk mechanical properties reported in the literature. Comparison between the unirradiated micro-tensile properties of W-5Re and W-5Ta with W showed that, as expected, W-5Re was softer than W whilst W-5Ta had only minor differences in micro-tensile properties compared with W. The micro-tensile results of the irradiated W, W-5Ta and W-5Re showed an increase in strength and an almost complete loss of ductility compared to the unirradiated samples. In comparing micro-tensile results to nanoindentation measurements, it was found that micro-tensile offers comparable level of precision in measurement of irradiation hardening amongst W, W-5Ta and W-5Re. The implications of the results with respect to the future performance of tungsten-based materials in the divertors in fusion reactors are discussed in detail. Graphical abstract: [Figure not available: see fulltext.

A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies.

Purpose Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.Patients and methods Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide.Results DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.Conclusions Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL

SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 and correlates of protection in the UK general population

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable

Higher resolution total velocity Vt and Va finite-volume formulations on cell-centred structured and unstructured grids

Novel cell-centred finite-volume formulations are presented for incompressible and immiscible two-phase flow with both gravity and capillary pressure effects on structured and unstructured grids. The Darcy-flux is approximated by a control-volume distributed multipoint flux approximation (CVD-MPFA) coupled with a higher resolution approximation for convective transport. The CVD-MPFA method is used for Darcy-flux approximation involving pressure, gravity, and capillary pressure flux operators. Two IMPES formulations for coupling the pressure equation with fluid transport are presented. The first is based on the classical total velocity Vt fractional flow (Buckley Leverett) formulation, and the second is based on a more recent Va formulation. The CVD-MPFA method is employed for both Vt and Va formulations. The advantages of both coupled formulations are contrasted. The methods are tested on a range of structured and unstructured quadrilateral and triangular grids. The tests show that the resulting methods are found to be comparable for a number of classical cases, including channel flow problems. However, when gravity is present, flow regimes are identified where the Va formulation becomes locally unstable, in contrast to the total velocity formulation. The test cases also show the advantages of the higher resolution method compared to standard first-order single-point upstream weighting

De Broglie Wavelength of a Nonlocal Four-Photon

Superposition is one of the most distinct features of quantum theory and has been demonstrated in numerous realizations of Young's classical double-slit interference experiment and its analogues. However, quantum entanglement - a significant coherent superposition in multiparticle systems - yields phenomena that are much richer and more interesting than anything that can be seen in a one-particle system. Among them, one important type of multi-particle experiments uses path-entangled number-states, which exhibit pure higher-order interference and allow novel applications in metrology and imaging such as quantum interferometry and spectroscopy with phase sensitivity at the Heisenberg limit or quantum lithography beyond the classical diffraction limit. Up to now, in optical implementations of such schemes lower-order interference effects would always decrease the overall performance at higher particle numbers. They have thus been limited to two photons. We overcome this limitation and demonstrate a linear-optics-based four-photon interferometer. Observation of a four-particle mode-entangled state is confirmed by interference fringes with a periodicity of one quarter of the single-photon wavelength. This scheme can readily be extended to arbitrary photon numbers and thus represents an important step towards realizable applications with entanglement-enhanced performance.Comment: 19 pages, 4 figures, submitted on November 18, 200

STAT3 regulates the onset of oxidant-induced senescence in lung fibroblasts

Copyright © 2019 by the American Thoracic Society. Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown cause with a median survival of only 3 years. Other investigators and we have shown that fibroblasts derived from IPF lungs display characteristics of senescent cells, and that dysregulated activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) correlates with IPF progression. The question of whether STAT3 activation is involved in fibroblast senescence remains unanswered. We hypothesized that inhibiting STAT3 activation after oxidantinduced senescence would attenuate characteristics of the senescent phenotype. We aimed to characterize a model of oxidant-induced senescence in human lung fibroblasts and to determine the effect of inhibiting STAT3 activity on the development of senescence. Exposing human lung fibroblasts to 150 μM hydrogen peroxide (H2O2) resulted in increased senescence-associated β-galactosidase content and expression of p21 and IL-6, all of which are features of senescence. The shift into senescence was accompanied by an increase of STAT3 translocation to the nucleus and mitochondria. Additionally, Seahorse analysis provided evidence of increased mitochondrial respiration characterized by increased basal respiration, proton leak, and an associated increase in superoxide (O2-) production in senescent fibroblasts. Targeting STAT3 activity using the small-molecule inhibitor STA-21 attenuated IL-6 production, reduced p21 levels, decreased senescence-associated b-galactosidase accumulation, and restored normalmitochondrial function. The results of this study illustrate that stress-induced senescence in lung fibroblasts involves the activation of STAT3, which can be pharmacologically modulated

Eosinophil and T Cell Markers Predict Functional Decline in COPD Patients

BACKGROUND. The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS. Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION. Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION. These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.National Heart, Lung, and Blood Institute (NO1-HR-96140, NO1-HR-96141-001, NO1-HR-96144, NO1-HR-96143; NO1-HR-96145; NO1-HR-96142, R01HL086936-03); The Flight Attendant Medical Research Institute; the Jo-Ann F. LeBuhn Center for Chest Diseas

Early effects of oral administration of lafutidine with mosapride compared with lafutidine alone on intragastric pH values

<p>Abstract</p> <p>Background</p> <p>The ideal medication for treatment of acid related diseases should have a rapid onset of action to promote hemostasis and resolution of symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after a single oral administrations of lafutidine, is a newly synthesized H2-receptor antagonist, with mosapride 5 mg or lafutidine alone.</p> <p>Methods</p> <p>Ten <it>Helicobacter pylori </it>negative male subjects participated in this randomized, two-way crossover study. Intragastric pH was monitored continuously for 4 hours after a single oral administration of lafutidine 10 mg or lafutidine 10 mg with mosapride 5 mg (the lafutidine being administrated one hour after the mosapride). Each administration was separated by a 7-day washout period.</p> <p>Results</p> <p>The average pH during the 4-hour period after administration of lafutidine 10 mg with mosapride 5 mg was higher than after lafutidine 10 mg alone (median: 5.25 versus 4.58, respectively; <it>p </it>= 0.0318). During the 3–4 hour study period, lafutidine 10 mg with mosapride 5 mg provided a higher pH, compared to lafutidine 10 mg alone (median: 7.28 versus 6.42; <it>p </it>= 0.0208).</p> <p>Conclusion</p> <p>In <it>H. pylori </it>negative healthy male subjects, an oral dose of lafutidine 10 mg with mosapride 5 mg more rapidly increased intragastric pH than lafutidine 10 mg alone.</p