185 research outputs found

    The importance of the urologist in male oncology fertility preservation.

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    To demonstrate that surgical sperm retrieval (SSR) and spermatogonial stem cell retrieval (SSCR) in an oncological context are safe and successful. This a retrospective study in a tertiary hospital in the UK. Patients requiring fertility preservation from December 2017 to January 2020 were included. Data were analysed with Microsoft Excel 2016 and the Statistical Package for the Social Sciences (version 20). Among 1264 patients referred to the Reproductive Medical Unit at the University College of London Hospitals for cryopreservation prior to gonadotoxic treatment, 39 chose to go forward with SSR/SSCR because they presented as azoo-/cryptozoospermic or an inability to masturbate/ejaculate. Interventions were testicular sperm extraction (23 patients) or aspiration (one), electroejaculation (one), and testicular wedge biopsy for SSCR (14). The median (range) age was 15.0 (10-65) years and the median testosterone level was 4.4 nmoL/L. Primary diagnoses were sarcoma in 11 patients, leukaemia in nine, lymphoma in eight, testicular tumour in five, other oncological haematological entities in two, other solid cancers in two, while two patients had non-oncological haematological diseases. SSR/SSCR could be offered within 7.5 days on average. Chemotherapy could follow within 2 days from SSR/SSCR, and bone marrow transplant occurred within 19.5 days (all expressed as medians). The success rate for SSR was 68.0% (at least one vial/straw collected). The mean (SD) Johnsen score of testicular biopsies was 5.23 (2.25) with a trend towards positive correlation with SSR success (P = 0.07). However, age, hormonal profile and type of cancer did not predict SSR outcome. We show that SSR and SSCR in an oncological context are valid treatment options with a high success rate for patients in which sperm cryopreservation from semen is impossible. By providing an effective pathway, fertility preservation is possible with minimal delay to oncological treatment

    Interception of the Bycroft-Gowland Intermediate in the Enzymatic Macrocyclization of Thiopeptides

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    Thiopeptides are a broad class of macrocyclic, heavily modified peptide natural products that are unified by the presence of a substituted, nitrogen-containing heterocycle core. Early work indicated that this core might be fashioned from two dehydroalanines by an enzyme-catalyzed aza-[4 + 2] cycloaddition to give a cyclic-hemiaminal intermediate. This common intermediate could then follow a reductive path toward a dehydropiperidine, as in the thiopeptide thiostrepton, or an aromatization path to yield the pyridine groups observed in many other thiopeptides. Although several of the enzymes proposed to perform this cycloaddition have been reconstituted, only pyridine products have been isolated and any hemiaminal intermediates have yet to be observed. Here, we identify the conditions and substrates that decouple the cycloaddition from subsequent steps and allow interception and characterization of this long hypothesized intermediate. Transition state modeling indicates that the key amide-iminol tautomerization is the major hurdle in an otherwise energetically favorable cycloaddition. An anionic model suggests that deprotonation and polarization of this amide bond by TbtD removes this barrier and provides a sufficient driving force for facile (stepwise) cycloaddition. This work provides evidence for a mechanistic link between disparate cyclases in thiopeptide biosynthesis

    Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

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    Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

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    The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

    Search for neutral resonances decaying into a Z boson and a pair of b jets or τ leptons

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    A search is performed for a new resonance decaying into a lighter resonance and a Z boson. Two channels are studied, targeting the decay of the lighter resonance into either a pair of oppositely charged τ leptons or a bb‾ pair. The Z boson is identified via its decays to electrons or muons. The search exploits data collected by the CMS experiment at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.8 fb −1 . No significant deviations are observed from the standard model expectation and limits are set on production cross sections and parameters of two-Higgs-doublet models

    Phenomenological MSSM interpretation of CMS searches in pp collisions at √s=7 and 8 TeV

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    Searches for new physics by the CMS collaboration are interpreted in the framework of the phenomenological minimal supersymmetric standard model (pMSSM). The data samples used in this study were collected at root s = 7 and 8 TeV and have integrated luminosities of 5.0 fb(-1) and 19.5 fb(-1), respectively. A global Bayesian analysis is performed, incorporating results from a broad range of CMS supersymmetry searches, as well as constraints from other experiments. Because the pMSSM incorporates several well-motivated assumptions that reduce the 120 parameters of the MSSM to just 19 parameters defined at the electroweak scale, it is possible to assess the results of the study in a relatively straightforward way. Approximately half of the model points in a potentially accessible subspace of the pMSSM are excluded, including all pMSSM model points with a gluino mass below 500 GeV, as well as models with a squark mass less than 300 GeV. Models with chargino and neutralino masses below 200 GeV are disfavored, but no mass range of model points can be ruled out based on the analyses considered. The nonexcluded regions in the pMSSM parameter space are characterized in terms of physical processes and key observables, and implications for future searches are discussed

    Measurements of t(t)over-bar charge asymmetry using dilepton final states in pp collisions at root s=8 TeV

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    Search for lepton flavour violating decays of heavy resonances and quantum black holes to an eμ pair in proton–proton collisions at √s = 8 TeV

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    A search for narrow resonances decaying to an electron and a muon is presented. The eμ mass spectrum is also investigated for non-resonant contributions from the production of quantum black holes (QBHs). The analysis is performed using data corresponding to an integrated luminosity of 19.7 fb-1 collected in proton-proton collisions at a centre-of-mass energy of 8 TeV with the CMS detector at the LHC. With no evidence for physics beyond the standard model in the invariant mass spectrum of selected eμ pairs, upper limits are set at 95&nbsp;% confidence level on the product of cross section and branching fraction for signals arising in theories with charged lepton flavour violation. In the search for narrow resonances, the resonant production of τ sneutrino in R-parity violating supersymmetry is considered. The τ sneutrino is excluded for masses below 1.28 TeV for couplings λ132= λ231= λ311′= 0.01 , and below 2.30 TeV for λ132= λ231= 0.07 and λ311′= 0.11. These are the most stringent limits to date from direct searches at high-energy colliders. In addition, the resonance searches are interpreted in terms of a model with heavy partners of the Z boson and the photon. In a framework of TeV-scale quantum gravity based on a renormalization of Newton’s constant, the search for non-resonant contributions to the eμ mass spectrum excludes QBH production below a threshold mass Mth of 1.99 TeV. In models that invoke extra dimensions, the bounds range from 2.36 TeV for one extra dimension to 3.63 TeV for six extra dimensions. This is the first search for QBHs decaying into the eμ final state

    Measurement of the integrated and differential t(t)over-bar production cross sections for high-p(T) top quarks in pp collisions at root s=8 TeV

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