503 research outputs found
Synthesis, in vitro, and in vivo evaluation of novel N-phenylindazolyl diarylureas as potential anti-cancer agents.
Novel N-phenylindazole based diarylureas have been designed, synthesized and evaluated as potential anticancer agents. In vitro cell viability studies of these derivatives illustrate good potency with IC50 values in the range of 0.4â50 ÎŒM in several cancer cell lines including murine metastatic breast cancer 4T1, murine glioblastoma GL261, human triple negative breast cancer MDA-MB-231, human pancreatic cancer MIAPaCa-2, and human colorectal cancer cell line WiDr. The ester group in the lead compound 8i was modified to incorporate amino-amides to increase solubility and stability while retaining biological activity. Further in vitro studies reveal that lead candidates inhibit tube length in HUVEC cells. In vivo systemic toxicity studies indicate that these candidate compounds are well tolerated in mice without any significant side effects. Anticancer efficacy studies in WiDr tumor xenograft and 4T1 tumor syngraft models demonstrate that the lead candidate 11 exhibits significant antitumor properties as a single agent in these tumor models
Cryoballoon pulmonary vein isolation as first-line treatment of typical atrial flutter: long-term outcomes of the CRAFT trial
\ua9 The Author(s) 2024.Background: CRAFT was an international, multicentre, randomised controlled trial across 11 sites in the United UK and Switzerland. Given the evidence that pulmonary vein triggers may be responsible for atrial flutter (AFL) as well as atrial fibrillation (AF), we hypothesised that cryoballoon pulmonary vein isolation (PVI) would provide greater symptomatic arrhythmia reduction than cavotricuspid isthmus (CTI) ablation, whilst also reducing the subsequent burden of AF. Twelve-month outcomes were previously reported. In this study, we report the extended outcomes of the CRAFT study to 36 months. Methods: Patients with typical AFL and no evidence of AF were randomised 1:1 to cryoballoon PVI or radiofrequency CTI. All patients received an implantable loop recorder (ILR) for continuous cardiac rhythm monitoring. The primary outcome was time-to-symptomatic arrhythmia recurrence > 30 s. Secondary outcomes included time-to-first-AF episode â„ 2 min. The composite safety outcome included death, stroke and procedural complications. Results: A total of 113 patients were randomised to cryoballoon PVI (n = 54) or radiofrequency CTI ablation (n = 59). Ninety-one patients reconsented for extended follow-up beyond 12 months. There was no difference in the primary outcome between arms, with the primary outcome occurring in 12 PVI vs 11 CTI patients (HR 0.97; 95% CI 0.43â2.20; p = 0.994). AF â„ 2 min was significantly less frequent in the PVI arm, affecting 26 PVI vs 36 CTI patients (HR 0.48; 95% CI 0.29â0.79; p = 0.004). The composite safety outcome occurred in 5 PVI and 6 CTI patients (p = 0.755). Conclusion: Cryoballoon PVI shows similar efficacy to radiofrequency CTI ablation in reducing symptomatic arrhythmia recurrence in patients presenting with isolated typical AFL but significantly reduces the occurrence of subsequent AF. Graphical Abstract: (Figure presented.)
No Humanitarian Intervention in Asian Genocides: How Possible and Legitimate?
This paper addresses an important empirical puzzle: why has the United States, without exception, chosen not to intervene in the six humanitarian catastrophes in post-war Asia, namely in Indonesia, East Pakistan/Bangladesh, Cambodia, East Timor, Sri Lanka and Myanmar? We use an eclectic approach that blends arguments about the international normative structure and geostrategic interests to examine what has made the absence of humanitarian intervention in Asia by the US possible and legitimate. Specifically, we focus on the paradox between calls for humanitarian intervention and the historically and geographically contingent social construction of the norms of humanity, national sovereignty and UN-backed multilateralism in conjunction with US and Chinese concerns over their regional geostrategic interests. The normative narratives about race, âcommunistsâ, âterroristsâ, international order and inclusive multilateral process, and geostrategic interests of the US and China combine to make non-intervention possible and legitimate
Measurement of the lifetime
Using a data set corresponding to an integrated luminosity of ,
collected by the LHCb experiment in collisions at centre-of-mass energies
of 7 and 8 TeV, the effective lifetime in the
decay mode, , is measured to be ps. Assuming
conservation, corresponds to the lifetime of the light
mass eigenstate. This is the first measurement of the effective
lifetime in this decay mode.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-017.htm
Measurement of the mass and lifetime of the baryon
A proton-proton collision data sample, corresponding to an integrated
luminosity of 3 fb collected by LHCb at and 8 TeV, is used
to reconstruct , decays. Using the , decay mode for calibration, the lifetime ratio and absolute
lifetime of the baryon are measured to be \begin{align*}
\frac{\tau_{\Omega_b^-}}{\tau_{\Xi_b^-}} &= 1.11\pm0.16\pm0.03, \\
\tau_{\Omega_b^-} &= 1.78\pm0.26\pm0.05\pm0.06~{\rm ps}, \end{align*} where the
uncertainties are statistical, systematic and from the calibration mode (for
only). A measurement is also made of the mass difference,
, and the corresponding mass, which
yields \begin{align*} m_{\Omega_b^-}-m_{\Xi_b^-} &= 247.4\pm3.2\pm0.5~{\rm
MeV}/c^2, \\ m_{\Omega_b^-} &= 6045.1\pm3.2\pm 0.5\pm0.6~{\rm MeV}/c^2.
\end{align*} These results are consistent with previous measurements.Comment: 11 pages, 5 figures, All figures and tables, along with any
supplementary material and additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-008.htm
Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at âs=7 TeV
Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected
by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the
form of an enhancement of pairs of like-sign charged pions with small four-momentum
difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source
is investigated, determining both the correlation radius and the chaoticity parameter. The
measured correlation radius is found to increase as a function of increasing charged-particle
multiplicity, while the chaoticity parameter is seen to decreas
Constraints on the unitarity triangle angle from Dalitz plot analysis of decays
The first study is presented of CP violation with an amplitude analysis of
the Dalitz plot of decays, with , and . The analysis is based on a data sample corresponding to
of collisions collected with the LHCb detector. No
significant CP violation effect is seen, and constraints are placed on the
angle of the unitarity triangle formed from elements of the
Cabibbo-Kobayashi-Maskawa quark mixing matrix. Hadronic parameters associated
with the decay are determined for the first time. These
measurements can be used to improve the sensitivity to of existing and
future studies of the decay.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-059.html;
updated to correct figure 9 (numerical results unchanged
Observation of the decay
The decay is observed in collision
data corresponding to an integrated luminosity of 3 fb recorded by the
LHCb detector at centre-of-mass energies of 7 TeV and 8 TeV. This is the first
observation of this decay channel, with a statistical significance of 15
standard deviations. The mass of the meson is measured to be
MeV/c. The branching fraction ratio
is measured to be 0.0115\,\pm\, 0.0012\, ^{+0.0005}_{-0.0009}.
In both cases, the first uncertainty is statistical and the second is
systematic. No evidence for non-resonant or decays is found.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2015-033.htm
Study of J /Ï production in Jets
The production of J/Ï mesons in jets is studied in the forward region of proton-proton collisions using data collected with the LHCb detector at a center-of-mass energy of 13 TeV. The fraction of the jet transverse momentum carried by the J/Ï meson, z(J/Ï)âĄpT(J/Ï)/pT(jet), is measured using jets with pT(jet)>20 GeV in the pseudorapidity range 2.5<η(jet)<4.0. The observed z(J/Ï)distribution for J/Ï mesons produced in b-hadron decays is consistent with expectations. However, the results for prompt J/Ï production do not agree with predictions based on fixed-order nonrelativistic QCD. This is the first measurement of the pT fraction carried by prompt J/Ï mesons in jets at any experiment
Model-independent evidence for contributions to decays
The data sample of decays acquired with the
LHCb detector from 7 and 8~TeV collisions, corresponding to an integrated
luminosity of 3 fb, is inspected for the presence of or
contributions with minimal assumptions about
contributions. It is demonstrated at more than 9 standard deviations that
decays cannot be described with
contributions alone, and that contributions play a dominant role in
this incompatibility. These model-independent results support the previously
obtained model-dependent evidence for charmonium-pentaquark
states in the same data sample.Comment: 21 pages, 12 figures (including the supplemental section added at the
end
- âŠ