Stepped vitrification technique for human ovarian tissue cryopreservation

The advantage of stepped vitrification (SV) is avoiding ice crystal nucleation, while decreasing the toxic effects of high cryoprotectant concentrations. We aimed to test this method for human ovarian tissue cryopreservation. Ovarian cortex was taken from 7 fertile adult women. Samples were subjected to an SV protocol performed in an automatic freezer, which allowed sample transfer to ever higher concentrations of dimethyl sulfoxide (DMSO) as the temperature was reduced. Histological evaluation of the vitrified-warmed tissue showed large numbers of degenerated follicles after 24 hours of in vitro culture. We therefore evaluated DMSO perfusion rates by X-ray computed tomography, ice crystal formation by freeze-substitution, and cell toxicity by transmission electron microscopy, seeking possible reasons why follicles degenerated. Although cryoprotectant perfusion was considered normal and no ice crystals were formed in the tissue, ultrastructural analysis detected typical signs of DMSO toxicity, such as mitochondria degeneration, alterations in chromatin condensation, cell vacuolization and extracellular matrix swelling in both stromal and follicular cells. The findings indicated that the method failed to preserve follicles due to the high concentrations of DMSO used. However, adaptations can be made to avoid toxicity to follicles caused by elevated levels of cryoprotectants.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2016/22947-

First-Line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer.

Nivolumab has been associated with longer overall survival than docetaxel among patients with previously treated non-small-cell lung cancer (NSCLC). In an open-label phase 3 trial, we compared first-line nivolumab with chemotherapy in patients with programmed death ligand 1 (PD-L1)-positive NSCLC. We randomly assigned, in a 1:1 ratio, patients with untreated stage IV or recurrent NSCLC and a PD-L1 tumor-expression level of 1% or more to receive nivolumab (administered intravenously at a dose of 3 mg per kilogram of body weight once every 2 weeks) or platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). Patients receiving chemotherapy could cross over to receive nivolumab at the time of disease progression. The primary end point was progression-free survival, as assessed by means of blinded independent central review, among patients with a PD-L1 expression level of 5% or more. Among the 423 patients with a PD-L1 expression level of 5% or more, the median progression-free survival was 4.2 months with nivolumab versus 5.9 months with chemotherapy (hazard ratio for disease progression or death, 1.15; 95% confidence interval [CI], 0.91 to 1.45; P=0.25), and the median overall survival was 14.4 months versus 13.2 months (hazard ratio for death, 1.02; 95% CI, 0.80 to 1.30). A total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy. Treatment-related adverse events of any grade occurred in 71% of the patients who received nivolumab and in 92% of those who received chemotherapy. Treatment-related adverse events of grade 3 or 4 occurred in 18% of the patients who received nivolumab and in 51% of those who received chemotherapy. Nivolumab was not associated with significantly longer progression-free survival than chemotherapy among patients with previously untreated stage IV or recurrent NSCLC with a PD-L1 expression level of 5% or more. Overall survival was similar between groups. Nivolumab had a favorable safety profile, as compared with chemotherapy, with no new or unexpected safety signals. (Funded by Bristol-Myers Squibb and others; CheckMate 026 ClinicalTrials.gov number, NCT02041533 .)

Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Azimuthal anisotropy and correlations in p+p, d+Au and Au+Au collisions at 200 GeV

We present the first measurement of directed flow ($v_1$) at RHIC. $v_1$ is found to be consistent with zero at pseudorapidities $\eta$ from -1.2 to 1.2, then rises to the level of a couple of percent over the range $2.4 < |\eta| < 4$. The latter observation is similar to data from NA49 if the SPS rapidities are shifted by the difference in beam rapidity between RHIC and SPS. Back-to-back jets emitted out-of-plane are found to be suppressed more if compared to those emitted in-plane, which is consistent with {\it jet quenching}. Using the scalar product method, we systematically compared azimuthal correlations from p+p, d+Au and Au+Au collisions. Flow and non-flow from these three different collision systems are discussed.Comment: Quark Matter 2004 proceeding, 4 pages, 3 figure

Azimuthal anisotropy: the higher harmonics

We report the first observations of the fourth harmonic (v_4) in the azimuthal distribution of particles at RHIC. The measurement was done taking advantage of the large elliptic flow generated at RHIC. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 4 pages, 6 figures, contribution to the Quark Matter 2004 proceeding

All-optical switching and strong coupling using tunable whispering-gallery-mode microresonators

We review our recent work on tunable, ultrahigh quality factor whispering-gallery-mode bottle microresonators and highlight their applications in nonlinear optics and in quantum optics experiments. Our resonators combine ultra-high quality factors of up to Q = 3.6 \times 10^8, a small mode volume, and near-lossless fiber coupling, with a simple and customizable mode structure enabling full tunability. We study, theoretically and experimentally, nonlinear all-optical switching via the Kerr effect when the resonator is operated in an add-drop configuration. This allows us to optically route a single-wavelength cw optical signal between two fiber ports with high efficiency. Finally, we report on progress towards strong coupling of single rubidium atoms to an ultra-high Q mode of an actively stabilized bottle microresonator.Comment: 20 pages, 24 figures. Accepted for publication in Applied Physics B. Changes according to referee suggestions: minor corrections to some figures and captions, clarification of some points in the text, added references, added new paragraph with results on atom-resonator interactio

Strange Resonance Production in p+p and Au+Au Collisions at RHIC Energies

Resonance yields and spectra from elementary p+p and Au+Au collisions at $\sqrt{s_{\rm NN}} =$ 200 GeV from the STAR experiment at RHIC are presented and discussed in terms of chemical and thermal freeze-out conditions. Thermal models do not adequately describe the yields of the resonance production in central Au+Au collisions. The approach to include elastic hadronic interactions between chemical freeze-out and thermal freeze-out suggests a time of $\Delta \tau>$5 fm/c.Comment: 4 pages, 7 figures, proceedings of the Quark Matter 2004, in Oakland, California, to be published in Journal of Physics G: Nuclear and Particle Physic

Identified particles at large transverse momenta in STAR in Au+Au collisions @ sqrt(s_NN) = 200 GeV

We report measurements of the ratios of identified hadrons (pi,K,p,Lambda) in Au+Au collisions at sqrt(s_NN) = 200 GeV as a function of both collision centrality and transverse momentum (p_T). Ratios of anti-baryon to baryon yields are independent of p_T within 2<p_T <6 GeV/c indicating that, for such a range, our measurements are inconsistent with theoretical pQCD calculations predicting a decrease due to a stronger contribution from valence quark scattering. For both strange and non-strange species, a strong baryon enhancement relative to meson yields is observed as a function of collision centrality in this intermediate p_T region, leading to p/pi and Lambda/K ratios greater than unity. The nuclear modification factor, R_cp (central relative to peripheral collisions), is used to illustrate the interplay between jet quenching and hadron production. The physics implications of these measurements are discussed with reference to different theoretical models.Comment: 5 pages, 4 figures. Proceedings of Quark Matter 2004 Conference, Jan 2004, Oakland, USA. Submitted to Journal of Physics

High-pTp_{T} electron distributions in d+Au and p+p collisions at RHIC

We present preliminary measurements of electron and positron spectra in d+Au and p+p collisions at $\sqrt{s_{NN}}=200$ GeV for $1.5 < p_{T} < 7.0$ GeV/c. These measurements were carried out using the STAR Time Projection Chamber (TPC) and the Barrel Electromagnetic calorimeter (EMC). Overall hadron rejection factors in the range of $10^{5}$ have been achieved. In this work we describe the measurement technique used to discriminate electrons from hadrons and compare the results for single electron spectra with Pythia based pQCD calculations for electrons from heavy-quark semi-leptonic decays.Comment: Quark Matter 2004 conference proceeding

Correlations and Fluctuations in STAR

We report measurements for the balance function, transverse momentum fluctuations, and net charge fluctuations from Au+Au collisions at 20, 130, and 200 GeV as well as p+p and d+Au collisions at 200 GeV using STAR at RHIC. For Au+Au collisions at 200 GeV, we observe a narrowing of the balance function in central collisions. We observe dynamic transverse momentum fluctuations at all incident energies. Observables related to transverse momentum fluctuations and net charge fluctuations are similar for peripheral Au+Au collisions and inclusive p+p collisions while central Au+Au collisions deviate significantly from HIJING predictions.Comment: 4 pages, 3 figures, Contribution to Quark Matter 2004 Proceeding