Evaluation of Microparticulate Ovarian Cancer Vaccine via Transdermal Route of Delivery

Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response. The vaccine microparticles were administered to C57BL/6 female mice via transdermal alone and in combination with the oral route. The transdermal vaccine was delivered using a metallic microneedle device, AdminPen™. Orally administered microparticles also included an M-cell targeting ligand, Aleuria aurantia lectin, to enhance the targeted uptake from microfold cells (M-cells) in Peyer\u27s patches of small intestine. In case of combination of routes, mice were given 5 transdermal doses and 5 oral doses administered alternatively, beginning with transdermal dose. At the end of vaccination, mice were challenged with live tumor cells. Vaccine alone resulted in around 1.5 times tumor suppression in case of transdermal and combination of routes at the end of 15th week when compared to controls. Inclusion of interleukins resulted in 3 times tumor suppression when administered with transdermal vaccine and around 9 times tumor suppression for the combination route of delivery in comparison to controls. These results were further potentiated by serum IgG, IgG1 and IgG2a titers. Moreover, CD8+ T-cell, CD4+ T-cell and NK (natural killer) cell populations in splenocytes were elevated in case of vaccinated mice. Thus, vaccine microparticles could trigger humoral as well as cellular immune response when administered transdermally and via combination of route of delivery. However overall, vaccine administered with interleukins, via combination of route, was found to be the most efficacious to suppress the tumor growth and lead to a protective immune response

Non-degenerate, three-wave mixing with the Josephson ring modulator

The Josephson ring modulator (JRM) is a device, based on Josephson tunnel junctions, capable of performing non-degenerate mixing in the microwave regime without losses. The generic scattering matrix of the device is calculated by solving coupled quantum Langevin equations. Its form shows that the device can achieve quantum-limited noise performance both as an amplifier and a mixer. Fundamental limitations on simultaneous optimization of performance metrics like gain, bandwidth and dynamic range (including the effect of pump depletion) are discussed. We also present three possible integrations of the JRM as the active medium in a different electromagnetic environment. The resulting circuits, named Josephson parametric converters (JPC), are discussed in detail, and experimental data on their dynamic range are found to be in good agreement with theoretical predictions. We also discuss future prospects and requisite optimization of JPC as a preamplifier for qubit readout applications.Comment: 21 pages, 16 figures, 4 table

Heisenberg-limited qubit readout with two-mode squeezed light

We show how to use two-mode squeezed light to exponentially enhance cavity-based dispersive qubit measurement. Our scheme enables true Heisenberg-limited scaling of the measurement, and crucially, is not restricted to small dispersive couplings or unrealistically long measurement times. It involves coupling a qubit dispersively to two cavities, and making use of a symmetry in the dynamics of joint cavity quadratures (a so-called quantum-mechanics-free subsystem). We discuss the basic scaling of the scheme and its robustness against imperfections, as well as a realistic implementation in circuit quantum electrodynamics.Comment: 5 pages, 4 figures, Supplemental Materia

Electron paramagnetic resonance study of ErSc2NC80

We present an electron paramagnetic resonance (EPR) study of ErSc2N@C80 fullerene in which there are two Er3+ sites corresponding to two different configurations of the ErSc2N cluster inside the C80 cage. For each configuration, the EPR spectrum is characterized by a strong anisotropy of the g factors (gx,y = 2.9, gz = 13.0 and gx,y = 5.3, gz = 10.9). Illumination within the cage absorption range (<600 nm) induces a rearrangement of the ErSc2N cluster inside the cage. We follow the temporal dependence of this rearrangement phenomenologically under various conditions.Comment: 7 pages, 7 figure

Effect of letrozole on masculinization of Siamese fighting fish (Betta splendens)

The aim of this study was to evaluate the effect of letrozole (a non-steroidal aromatase inhibitor) on masculinization of Siamese fighting fish (Betta splendens). Different doses of letrozole 50, 100, 150 and 200 ppm (mg/kg feed) were incorporated into diet and fed for periods of 30, 40 or 50 days. Immersion treatment of letrozole at selected doses (250, 500, 750 and 1,000?g/l) for 3 h each on third, fifth and eighth day-post-hatching (dph) (Trial 1) and fourth, sixth and eighth dph (Trial 2) was given.The oral administration of letrozole for 30, 40 or 50 days did not have any significant effect on the sex ratio of B. splendens. The immersion treatment of letrozole induced 100% masculinization at 500 and 1000?g/l in trial 1, while it yielded only 66.66 and 90% male population at 500 and 1000 ?g/l in Trial 2. The dietary administration of letrozole for 30 and 50 days caused tail deformities and/or rudimentary and absence of dorsal fin. The progeny testing of males from letrozole treated (both oral and immersion) groups indicate that the sex ratio of progenies of each of the males tested did not differ significantly from that of control, indicating that all those males carried XY genotype. Letrozole treatments suppressed ovarian development (atretic oocytes were common). However, the testicular development was unaffected. The study revealed that immersion treatment of letrozole was more effective in inducing masculinization of B. splendens than the oral administration of letrozole

Alignments in quasar polarizations: pseudoscalar-photon mixing in the presence of correlated magnetic fields

We investigate the effects of pseudoscalar-photon mixing on electromagnetic radiation in the presence of correlated extragalactic magnetic fields. We model the Universe as a collection of magnetic domains and study the propagation of radiation through them. This leads to correlations between Stokes parameters over large scales and consistently explains the observed large-scale alignment of quasar polarizations at different redshifts within the framework of the big bang model.Comment: 12 pages, 5 figures, version published in PR

Best chirplet chain: near-optimal detection of gravitational wave chirps

The list of putative sources of gravitational waves possibly detected by the ongoing worldwide network of large scale interferometers has been continuously growing in the last years. For some of them, the detection is made difficult by the lack of a complete information about the expected signal. We concentrate on the case where the expected GW is a quasi-periodic frequency modulated signal i.e., a chirp. In this article, we address the question of detecting an a priori unknown GW chirp. We introduce a general chirp model and claim that it includes all physically realistic GW chirps. We produce a finite grid of template waveforms which samples the resulting set of possible chirps. If we follow the classical approach (used for the detection of inspiralling binary chirps, for instance), we would build a bank of quadrature matched filters comparing the data to each of the templates of this grid. The detection would then be achieved by thresholding the output, the maximum giving the individual which best fits the data. In the present case, this exhaustive search is not tractable because of the very large number of templates in the grid. We show that the exhaustive search can be reformulated (using approximations) as a pattern search in the time-frequency plane. This motivates an approximate but feasible alternative solution which is clearly linked to the optimal one. [abridged version of the abstract]Comment: 23 pages, 9 figures. Accepted for publication in Phys. Rev D Some typos corrected and changes made according to referee's comment

Singular value decomposition in parametrised tests of post-Newtonian theory

Various coefficients of the 3.5 post-Newtonian (PN) phasing formula of non-spinning compact binaries moving in circular orbits is fully characterized by the two component masses. If two of these coefficients are independently measured, the masses can be estimated. Future gravitational wave observations could measure many of the 8 independent PN coefficients calculated to date. These additional measurements can be used to test the PN predictions of the underlying theory of gravity. Since all of these parameters are functions of the two component masses, there is strong correlation between the parameters when treated independently. Using Singular Value Decomposition of the Fisher information matrix, we remove this correlations and obtain a new set of parameters which are linear combinations of the original phasing coefficients. We show that the new set of parameters can be estimated with significantly improved accuracies which has implications for the ongoing efforts to implement parametrised tests of PN theory in the data analysis pipelines.Comment: 17 pages, 6 figures, Accepted for publication in Classical and Quantum Gravity (Matches with the published version