Entanglement by linear SU(2) transformations: generation and evolution of quantum vortex states

We consider the evolution of a two-mode system of bosons under the action of a Hamiltonian that generates linear SU(2) transformations. The Hamiltonian is generic in that it represents a host of entanglement mechanisms, which can thus be treated in a unified way. We start by solving the quantum dynamics analytically when the system is initially in a Fock state. We show how the two modes get entangled by evolution to produce a coherent superposition of vortex states in general, and a single vortex state under certain conditions. The degree of entanglement between the modes is measured by finding the explicit analytical dependence of the Von Neumann entropy on the system parameters. The reduced state of each mode is analyzed by means of its correlation function and spatial coherence function. Remarkably, our analysis is shown to be equally as valid for a variety of initial states that can be prepared from a two-mode Fock state via a unitary transformation and for which the results can be obtained by mere inspection of the corresponding results for an initial Fock state. As an example, we consider a quantum vortex as the initial state and also find conditions for its revival and charge conjugation. While studying the evolution of the initial vortex state, we have encountered and explained an interesting situation in which the entropy of the system does not evolve whereas its wave function does. Although the modal concept has been used throughout the paper, it is important to note that the theory is equally applicable for a two-particle system in which each particle is represented by its bosonic creation and annihilation operators.Comment: 6 figure

Off Resonant Pumping for Transition from Continuous to Discrete Spectrum and Quantum Revivals in Systems in Coherent States

We show that in parametrically driven systems and, more generally, in systems in coherent states, off-resonant pumping can cause a transition from a continuum energy spectrum of the system to a discrete one, and result in quantum revivals of the initial state. The mechanism responsible for quantum revivals in the present case is different from that in the non-linear wavepacket dynamics of systems such as Rydberg atoms. We interpret the reported phenomena as an optical analog of Bloch oscillations realized in Fock space and propose a feasible scheme for inducing Bloch oscillations in trapped ions.Comment: 5 pages, 4 figures, submitted to Jnl. of Optics

General relativistic plasma in higher dimensional space time

The well known (3+1) decomposition of Thorne and Macdonald is invoked to write down the Einstein-Maxwell equations generalised to (d+1) dimensions and also to formulate the plasma equations in a flat FRW like spacetime in higher dimensions (HD). Assuming an equation of state for the background metric we find solutions as also dispersion relations in different regimes of the universe in a unified manner both for magnetised(un) cold plasma. We find that for a free photon in expanding background we get maximum redshift in 4D spacetime, while for a particular dimension it is so in pre recombination era. Further wave propagation in magnetised plasma is possible for a restricted frequency range only, depending on the number of dimensions. Relevant to point out that unlike the special relativistic result this allowed range evolves with time. Interestingly the dielectric constant of the plasma media remains constant, not sharing the expansion of the background, which generalises a similar 4D result of Holcomb-Tajima in radiation background to the case of higher dimensions with cosmic matter obeying an equation of state . Further, analogous to the flat space static case we observe the phenomenon of Faraday rotation in higher dimensional case also.Comment: 17 pages, 3 figure

Constraints on the spectral index of polarized synchrotron emission from WMAP and Faraday-corrected S-PASS data

We constrain the spectral index of polarized synchrotron emission, $\beta_s$, by correlating the recently released 2.3 GHz S-Band Polarization All Sky Survey (S-PASS) data with the 23 GHz 9-year Wilkinson Microwave Anisotropy Probe (WMAP) sky maps. We sub-divide the S-PASS field, which covers the Southern Ecliptic hemisphere, into $15^{\circ}\times 15^{\circ}$ regions, and estimate the spectral index of polarized synchrotron emission within each region using a simple but robust T-T plot technique. Three different versions of the S-PASS data are considered, corresponding to either no correction for Faraday rotation; Faraday correction based on the rotation measure model presented by the S-PASS team; or Faraday correction based on a rotation measure model presented by Hutschenreuter and En{\ss}lin. We find that the correlation between S-PASS and WMAP is strongest when applying the S-PASS model. Adopting this correction model, we find that the mean spectral index of polarized synchrotron emission gradually steepens from $\beta_s\approx-2.8$ at low Galactic latitudes to $\beta_s\approx-3.2$ at high Galactic latitudes, in good agreement with previously published results. Finally, we consider two special cases defined by the BICEP2 and SPIDER fields, and obtain mean estimates of $\beta_{BICEP2}=-3.22\pm0.06$ and $\beta_{SPIDER}=-3.21\pm0.03$, respectively. Adopting the WMAP 23 GHz sky map bandpass filtered to including angular scales only between $2^{\circ}$ and $10^{\circ}$ as a spatial template, we constrain the root-mean-square synchrotron polarization amplitude to be less than $0.03\mu K$ ($0.009\mu K$) at 90 GHz (150 GHz) for the BICEP2 field, corresponding roughly to a tensor-to-scalar ratio of $r\lesssim0.02$ ($r\lesssim0.005$), respectively. Very similar constraints are obtained for the SPIDER field.Comment: 14 pages, 13 Figures, to be submitted to A&

Clinical benefit in Phase-I trials of novel molecularly targeted agents: does dose matter?

Phase-I trials traditionally involve dose-escalation to determine the maximal tolerated dose (MTD). With conventional chemotherapy, efficacy is generally deemed to be dose-dependent, but the same may not be applicable to molecularly targeted agents (MTAs). We analysed consecutive patients included in Phase-I trials at the Royal Marsden Hospital from 5 January 2005 to 6 June 2006. We considered only trials of monotherapy MTAs in which the MTD was defined. Three patient cohorts (A, B, and C) were identified according to the dose received as a percentage of the final trial MTD (0–33%, 34–65%, >66%). Potential efficacy was assessed using the non-progression rate (NPR), that is, complete/partial response or stable disease for at least 3 months by RECIST. A total of 135 patients having progressive disease before enrolment were analysed from 15 eligible trials. Median age was 57 years (20–86); male : female ratio was 1.8 : 1. Cohort A, B, and C included 28 (21%), 22 (16%), and 85 (63%) patients; NPR at 3 and 6 months was 21% and 11% (A), 50% and 27% (B), 31% and 14% (C), respectively, P=0.9. Median duration of non-progression (17 weeks; 95% CI=13–22) was not correlated with the MTD level, P=0.9. Our analysis suggests that the potential for clinical benefit is not confined to patients treated at doses close to the MTD in Phase-I trials of MTAs

Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study

Background: Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour activity in various models. In this first-in-human study, we assessed the safety and activity of trastuzumab duocarmazine in patients with advanced solid tumours. Methods: We did a phase 1 dose-escalation and dose-expansion study. The dose-escalation cohort comprised patients aged 18 years or older enrolled from three academic hospitals in Belgium, the Netherlands, and the UK with locally advanced or metastatic solid tumours with variable HER2 status who were refractory to standard cancer treatment. A separate cohort of patients were enrolled to the dose-expansion phase from 15 hospitals in Belgium, the Netherlands, Spain, and the UK. Dose-expansion cohorts included patients aged 18 years or older with breast, gastric, urothelial, or endometrial cancer with at least HER2 immunohistochemistry 1+ expression and measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST). Trastuzumab duocarmazine was administered intravenously on day 1 of each 3-week cycle. In the dose-escalation phase, trastuzumab duocarmazine was given at doses of 0.3 mg/kg to 2.4 mg/kg (3 + 3 design) until disease progression or unacceptable toxicity. The primary endpoint of the dose-escalation phase was to assess safety and ascertain the recommended phase 2 dose, which would be the dose used in the dose-expansion phase. The primary endpoint of the dose-expansion phase was the proportion of patients achieving an objective response (complete response or partial response), as assessed by the investigator using RECIST version 1.1. This ongoing study is registered with ClinicalTrials.gov, number NCT02277717, and is fully recruited. Findings: Between Oct 30, 2014, and April 2, 2018, 39 patients were enrolled and treated in the dose-escalation phase and 146 patients were enrolled and treated in the dose-expansion phase. One dose-limiting toxic effect (death from pneumonitis) occurred at the highest administered dose (2.4 mg/kg) in the dose-escalation phase. One further death occurred in the dose-escalation phase (1.5 mg/kg cohort) due to disease progression, which was attributed to general physical health decline. Grade 3-4 treatment-related adverse events reported more than once in the dose-escalation phase were keratitis (n=3) and fatigue (n=2). Based on all available data, the recommended phase 2 dose was set at 1.2 mg/kg. In the dose-expansion phase, treatment-related serious adverse events were reported in 16 (11%) of 146 patients, most commonly infusion-related reactions (two [1%]) and dyspnoea (two [1%]). The most common treatment-related adverse events (grades 1-4) were fatigue (48 [33%] of 146 patients), conjunctivitis (45 [31%]), and dry eye (45 [31%]). Most patients (104 [71%] of 146) had at least one ocular adverse event, with grade 3 events reported in ten (7%) of 146 patients. No patients died from treatment-related adverse events and four patients died due to disease progression, which were attributed to hepatic failure (n=1), upper gastrointestinal haemorrhage (n=1), neurological decompensation (n=1), and renal failure (n=1). In the breast cancer dose-expansion cohorts, 16 (33%, 95% CI 20.4-48.4) of 48 assessable patients with HER2-positive breast cancer achieved an objective response (all partial responses) according to RECIST. Nine (28%, 95% CI 13.8-46.8) of 32 patients with HER2-low, hormone receptor-positive breast cancer and six (40%, 16.3-67.6) of 15 patients with HER2-low, hormone receptor-negative breast cancer achieved an objective response (all partial responses). Partial responses were also observed in one (6%, 95% CI 0.2-30.2) of 16 patients with gastric cancer, four (25%, 7.3-52.4) of 16 patients with urothelial cancer, and five (39%, 13.9-68.4) of 13 patients with endometrial cancer. Interpretation: Trastuzumab duocarmazine shows notable clinical activity in heavily pretreated patients with HER2-expressing metastatic cancer, including HER2-positive trastuzumab emtansine-resistant and HER2-low breast cancer, with a manageable safety profile. Further investigation of trastuzumab duocarmazine for HER2-positive breast cancer is ongoing and trials for HER2-low breast cancer and other HER2-expressing cancers are in preparation. Copyright (C) 2019 Elsevier Ltd. All rights reserved

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.

BACKGROUND: This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge. CASE PRESENTATION: A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1. CONCLUSION: This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights

Structural and photophysical templating of a conjugated polyelectrolyte with single-stranded DNA

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