Oral self-nanoemulsifying drug delivery systems for enhancing bioavailability and anticancer potential of fosfestrol: In vitro and in vivo characterization.

PURPOSE: The objective of the current research work was to fabricate a fosfestrol (FST)-loaded self-nanoemulsifying drug delivery system (SNEDDS) to escalate the oral solubility and bioavailability and thereby the effectiveness of FST against prostate cancer. METHODS: 32 full factorial design was employed, and the effect of lipid and surfactant mixtures on percentage transmittance, time required for self-emulsification, and drug release were studied. The optimized solid FST-loaded SNEDDS (FSTNE) was characterized for in vitro anticancer activity and Caco-2 cell permeability, and in vivo pharmacokinetic parameters. RESULTS: Using different ratios of surfactant and co-surfactant (Km) a pseudo ternary phase diagram was constructed. Thirteen liquid nano emulsion formulations (LNE-1 to LNE-13) were formulated at Km = 3:1. LNE-9 exhibited a higher % transmittance (99.25 ± 1.82 %) and a lower self-emulsification time (24 ± 0.32 s). No incompatibility was observed in FT-IR analysis. Within 20 min the solidified FST loaded LNE-9 (FSTNE) formulation showed almost complete drug release (98.20 ± 1.30 %) when compared to marketed formulation (40.36 ± 2.8 %), and pure FST (32 ± 3.3 %) in 0.1 N HCl. In pH 6.8 phosphate buffer, the release profiles are found moderately higher than in 0.1 N HCl. FSTNE significantly (P < 0.001) inhibited the PC-3 prostate cell proliferation and also caused apoptosis (P < 0.001) compared to FST. The in vitro Caco-2 cell permeability study results revealed 4.68-fold higher cell permeability of FSTNE than FST. Remarkably, 4.5-fold rise in bioavailability was observed after oral administration of FSTNE than plain FST. CONCLUSIONS: FSTNE remarkably enhanced the in vitro anticancer activity and Caco-2 cell permeability, and in vivo bioavailability of FST. Thus, FST-SNEDDS could be utilized as a potential carrier for effective oral treatment of prostate cancer.

Realizing tight-binding Hamiltonians using site-controlled coupled cavity arrays.

Analog quantum simulators rely on programmable and scalable quantum devices to emulate Hamiltonians describing various physical phenomenon. Photonic coupled cavity arrays are a promising alternative platform for realizing such simulators, due to their potential for scalability, small size, and high-temperature operability. However, programmability and nonlinearity in photonic cavities remain outstanding challenges. Here, using a silicon photonic coupled cavity array made up of [Formula: see text] high quality factor ([Formula: see text] up to[Formula: see text]) resonators and equipped with specially designed thermo-optic island heaters for independent control of cavities, we demonstrate a programmable photonic cavity array in the telecom regime, implementing tight-binding Hamiltonians with access to the full eigenenergy spectrum. We report a [Formula: see text] reduction in the thermal crosstalk between neighboring sites of the cavity array compared to traditional heaters, and then present a control scheme to program the cavity array to a given tight-binding Hamiltonian. The ability to independently program high-Q photonic cavities, along with the compatibility of silicon photonics to high volume manufacturing opens new opportunities for scalable quantum simulation using telecom regime infrared photons.

Three-Photon Excitation of InGaN Quantum Dots.

We demonstrate that semiconductor quantum dots can be excited efficiently in a resonant three-photon process, while resonant two-photon excitation is highly suppressed. Time-dependent Floquet theory is used to quantify the strength of the multiphoton processes and model the experimental results. The efficiency of these transitions can be drawn directly from parity considerations in the electron and hole wave functions in semiconductor quantum dots. Finally, we exploit this technique to probe intrinsic properties of InGaN quantum dots. In contrast to nonresonant excitation, slow relaxation of charge carriers is avoided, which allows us to measure directly the radiative lifetime of the lowest energy exciton states. Since the emission energy is detuned far from the resonant driving laser field, polarization filtering is not required and emission with a greater degree of linear polarization is observed compared to nonresonant excitation.

Morphological Comparison of the Maxillary Arch in Buccal and Palatal Canine Impaction among Asian Population of Gujarati Origin: A Hospital-Based Study.

Aim: To estimate the differences in the maxillary arch morphology in buccal and palatal canine impaction in an Asian population of Gujarati origin. Methodology: An institutional ethics committee's approval was acquired before the commencement of this study. Sixty subjects were enrolled in the study. Thirty subjects (20 females and 10 males) had a maxillary impacted canine either buccal or palatal and thirty control group participants were selected aged 13 to 18 years who sought orthodontic treatment at the tertiary health care center in Ahmedabad, Gujarat, in western India. Routine pre-treatment radiographs and dental plaster models with good anatomic details were recorded. Measurements of the inter-molar width, palatal depth, arch length, sum of the mesio-distal width of the upper incisors, and available arch space were recorded from prepared orthodontic study models using digital vernier calipers with an accuracy of 0.01 mm and brass wire. The ratio of palatal depth to inter-molar width (Ratio 1), arch length to inter-molar width (Ratio 2), and width of the maxillary incisors to available arch space (Ratio 3) were also secondarily calculated. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 21, IBM Inc. The normality of the data was assessed by the Shapiro−Wilk test. As the data was found to be normally distributed, bivariate analyses were also performed (one-way ANOVA test, Bonferroni post hoc correction). The level of statistical significance was set at a p-value less than 0.05. Results: The comparison of the inter-molar width, palatal depth, arch length, sum of the mesio-distal width of the upper incisors, available arch space, Ratio 1, Ratio 2, and Ratio 3 among controls and subjects with buccal and palatal canine impaction showed overall significant differences in the inter-molar width, palatal depth, arch length, sum of the mesio-distal width of the upper incisors, and available arch space when compared using one-way ANOVA as p < 0.05. Ratios 1, 2, and 3 also showed significant differences between the buccal and palatal canine impaction. Conclusion: An inadequate arch length (p < 0.0001) and a higher degree of crowding with reduced available arch space (p < 0.0001) may be considered as early risk factors for buccal maxillary canine impaction. An inadequate inter-molar width (p < 0.0001), and an increased palatal depth (p < 0.0001) with a clinically reduced mesiodistal width of the sum of maxillary incisors may be considered as risk factors for palatal maxillary canine impaction in an Asian population of Gujarati origin.

Transitions in Computational Complexity of Continuous-Time Local Open Quantum Dynamics.

We analyze the complexity of classically simulating continuous-time dynamics of locally interacting quantum spin systems with a constant rate of entanglement breaking noise. We prove that a polynomial time classical algorithm can be used to sample from the state of the spins when the rate of noise is higher than a threshold determined by the strength of the local interactions. Furthermore, by encoding a 1D fault tolerant quantum computation into the dynamics of spin systems arranged on two or higher dimensional grids, we show that for several noise channels, the problem of weakly simulating the output state of both purely Hamiltonian and purely dissipative dynamics is expected to be hard in the low-noise regime.

Convergence Guarantees for Discrete Mode Approximations to Non-Markovian Quantum Baths.

Non-Markovian effects are important in modeling the behavior of open quantum systems arising in solid-state physics, quantum optics as well as in study of biological and chemical systems. The non-Markovian environment is often approximated by discrete bosonic modes, thus mapping it to a Lindbladian or Hamiltonian simulation problem. While systematic constructions of such modes have been previously proposed, the resulting approximation lacks rigorous and general convergence guarantees. In this Letter, we show that under some physically motivated assumptions on the system-environment interaction, the finite-time dynamics of the non-Markovian open quantum system computed with a sufficiently large number of modes is guaranteed to converge to the true result. Furthermore, we show that this approximation error typically falls off polynomially with the number of modes. Our results lend rigor to classical and quantum algorithms for approximating non-Markovian dynamics.

Crux of Using the Cascaded Emission of a Three-Level Quantum Ladder System to Generate Indistinguishable Photons.

We investigate the degree of indistinguishability of cascaded photons emitted from a three-level quantum ladder system; in our case the biexciton-exciton cascade of semiconductor quantum dots. For the three-level quantum ladder system we theoretically demonstrate that the indistinguishability is inherently limited for both emitted photons and determined by the ratio of the lifetimes of the excited and intermediate states. We experimentally confirm this finding by comparing the quantum interference visibility of noncascaded emission and cascaded emission from the same semiconductor quantum dot. Quantum optical simulations produce very good agreement with the measurements and allow us to explore a large parameter space. Based on our model, we propose photonic structures to optimize the lifetime ratio and overcome the limited indistinguishability of cascaded photon emission from a three-level quantum ladder system.

Publisher Correction: Data-driven acceleration of photonic simulations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

On-chip integrated laser-driven particle accelerator.

Particle accelerators represent an indispensable tool in science and industry. However, the size and cost of conventional radio-frequency accelerators limit the utility and reach of this technology. Dielectric laser accelerators (DLAs) provide a compact and cost-effective solution to this problem by driving accelerator nanostructures with visible or near-infrared pulsed lasers, resulting in a 104 reduction of scale. Current implementations of DLAs rely on free-space lasers directly incident on the accelerating structures, limiting the scalability and integrability of this technology. We present an experimental demonstration of a waveguide-integrated DLA that was designed using a photonic inverse-design approach. By comparing the measured electron energy spectra with particle-tracking simulations, we infer a maximum energy gain of 0.915 kilo-electron volts over 30 micrometers, corresponding to an acceleration gradient of 30.5 mega-electron volts per meter. On-chip acceleration provides the possibility for a completely integrated mega-electron volt-scale DLA.

Data-driven acceleration of photonic simulations.

Designing modern photonic devices often involves traversing a large parameter space via an optimization procedure, gradient based or otherwise, and typically results in the designer performing electromagnetic simulations of a large number of correlated devices. In this paper, we investigate the possibility of accelerating electromagnetic simulations using the data collected from such correlated simulations. In particular, we present an approach to accelerate the Generalized Minimal Residual (GMRES) algorithm for the solution of frequency-domain Maxwell's equations using two machine learning models (principal component analysis and a convolutional neural network). These data-driven models are trained to predict a subspace within which the solution of the frequency-domain Maxwell's equations approximately lies. This subspace is then used for augmenting the Krylov subspace generated during the GMRES iterations, thus effectively reducing the size of the Krylov subspace and hence the number of iterations needed for solving Maxwell's equations. By training the proposed models on a dataset of wavelength-splitting gratings, we show an order of magnitude reduction (~10-50) in the number of GMRES iterations required for solving frequency-domain Maxwell's equations.

Photon Blockade in Weakly Driven Cavity Quantum Electrodynamics Systems with Many Emitters.

We use the scattering matrix formalism to analyze photon blockade in coherently driven cavity quantum electrodynamics systems with a weak drive. By approximating the weak coherent drive by an input single- and two-photon Fock state, we reduce the computational complexity of the transmission and the two-photon correlation function from exponential to polynomial in the number of emitters. This enables us to easily analyze cavity-based systems containing ∼50 quantum emitters with modest computational resources. Using this approach we study the coherence statistics of photon blockade while increasing the number of emitters for resonant and detuned multiemitter cavity quantum electrodynamics systems-we find that increasing the number of emitters worsens photon blockade in resonant systems, and improves it in detuned systems. We also analyze the impact of inhomogeneous broadening in the emitter frequencies on the photon blockade through this system.

Analytical level set fabrication constraints for inverse design.

Inverse design methods produce nanophotonic devices with arbitrary geometries that show high efficiencies as well as novel functionalities. Ensuring fabricability during optimization of these unrestricted device geometries is a major challenge for these design methods. In this work, we construct a fabrication constraint penalty function for level set geometry representations of these devices. This analytical penalty function limits both the gap size and boundary curvature of a device. We incorporate this penalty in a fully automated optical design flow using a quasi-Newton optimization method. The performance of our design method is evaluated by designing a series of waveguide demultiplexers (WDM) and mode converters with various footprints and minimum feature sizes. Finally, we design and experimentally characterize three WDMs with a 80 nm, 120 nm and 160 nm feature size.

Fully-automated optimization of grating couplers.

We present a gradient-based algorithm to design general 1D grating couplers without any human input from start to finish, including a choice of initial condition. We show that we can reliably design efficient couplers to have multiple functionalities in different geometries, including conventional couplers for single-polarization and single-wavelength operation, polarization-insensitive couplers, and wavelength-demultiplexing couplers. In particular, we design a fiber-to-chip blazed grating with under 0.2 dB insertion loss that requires a single etch to fabricate and no back-reflector.

Nonsingular defects and self-assembly of colloidal particles in cholesteric liquid crystals.

Cholesteric liquid crystals can potentially provide a means for tunable self-organization of colloidal particles. However, the structures of particle-induced defects and the ensuing elasticity-mediated colloidal interactions in these media remain much less explored and understood as compared to their nematic liquid crystal counterparts. Here we demonstrate how colloidal microspheres of varying diameter relative to the helicoidal pitch can induce dipolelike director field configurations in cholesteric liquid crystals, where these particles are accompanied by point defects and a diverse variety of nonsingular line defects forming closed loops. Using laser tweezers and nonlinear optical microscopy, we characterize the ensuing medium-mediated elastic interactions and three-dimensional colloidal assemblies. Experimental findings show a good agreement with numerical modeling based on minimization of the Landau-de Gennes free energy and promise both practical applications in the realization of colloidal composite materials and a means of controlling nonsingular topological defects that attract a great deal of fundamental interest.

Plane wave scattering from a plasmonic nanowire-film system with the inclusion of non-local effects.

In this paper we present a theoretical analysis of the electromagnetic response of a plasmonic nanowire-film system. The analytical solution accounts for both the dispersive as well as non-local nature of the plasmonic media. The physical structure comprises of a plasmonic nanowire made of a plasmonic metal such as gold or silver placed over a plasmonic film of the same material. Such a nanostructure exhibits a spectrum that is extremely sensitive to various geometric parameters such as spacer thickness and nanowire radius, which makes it favorable for various sensing applications. The non-locality of the plasmonic medium, which can be captured using the hydrodynamic model, significantly affects the resonant wavelength of this system for structures of small dimensions (~ less than 5 nm gap between the nanowire and the film). We present an analytical method that can be used to predict the effect of non-locality on the resonances of the system. To validate the analytical method, we also report a comparison of our analytical solution with a numerical Finite Difference Time Domain analysis (FDTD) of the same structure with the plasmonic medium being treated as local in nature.

Cephalometric study to test the reliability of anteroposterior skeletal discrepancy indicators using the twin block appliance.

BACKGROUND: The objectives of this study were to check the reliability of the five angular and two linear parameters for sagittal maxillo-mandibular discrepancy and to compare and correlate angular parameters with the ANB angle, and the linear parameter with Wits analysis. METHODS: The pre-treatment and post-functional lateral cephalograms of 25 subjects (17 males, 8 females) with class II division 1 malocclusion treated with twin block functional appliance were selected. Five angular (ANB, ß angle, APDI, YEN angle, W angle) and two linear (Wits analysis, App-Bpp) parameters were traced on both sets of cephalograms. Paired Student's t-test, one-way ANOVA, post hoc test, and Karl Pearson correlation statistical analysis were performed. RESULTS: All the parameters considered in our study showed highly significant difference in pre-treatment and post-functional values, suggesting their reliability (p < 0.0001). When ANB angle was compared with the other angular parameters, a highly significant change in the mean value of the difference in pre-treatment (T1) and post-functional (T2) values was noted (p < 0.001). No significant change was seen when comparing the mean value of the difference in T1 and T2 between linear parameters (p = 0.949). CONCLUSIONS: All the parameters used in the study can be reliably used to assess anteroposterior skeletal discrepancy. Whenever limitations of the ANB angle and Wits analysis are foreseen, the W angle and App-Bpp, respectively, can be reliably used. The YEN angle may reliably predict the post-functional change with the use of twin block appliance.

Comparative clinical evaluation of laterally positioned pedicle graft and subepithelial connective tissue graft in the treatment of Miller's Class I and II gingival recession: A 6 months study.

AIM: The purpose of the study was to compare clinical outcomes of laterally positioned pedicle graft (LPPG) and subepithelial connective tissue graft (SCTG) for treatment of Miller's Class I and II gingival recession defects, at the end of 6 months. MATERIALS AND METHODS: Sixty Miller's Class I or II gingival recession defects (≥3 mm) (n = 30 each) on the labial aspect of anterior teeth were treated by either of the above techniques. Clinical parameters including recession depth (RD), width of keratinized gingiva (WKG), percentage of root coverage (%RC), and complete RC were recorded at baseline and 6 months postoperatively. Data were recorded and statistical analysis was done for both intergroup and intragroup. STATISTICAL ANALYSIS USED: Paired t-test intragroup and Student's t-test intergroup. RESULTS: In LPPG, RD decreased from 4.9 ± 0.99 mm to 1.1 ± 0.3 mm and WKG increased from 0.7 ± 0.87 to 4.5 ± 0.86 mm at 6 months, while in SCTG, RD decreased from 4.67 ± 1.12 mm to 0.46 ± 0.68 mm and WKG increased from 1.1 ± 0.99 to 5.33 ± 0.72 mm at 6 months postoperatively. The values of the soft tissue coverage remained stable for 6 months. CONCLUSIONS: Highly significant and effective soft tissue coverage was obtained by both techniques. LPPG resulted in effective soft tissue coverage for isolated deep narrow defects while SCTG in isolated and multiple, deep narrow and wide defects.

Full-wave electromagentic analysis of a plasmonic nanoparticle separated from a plasmonic film by a thin spacer layer.

This paper presents a theoretical analysis of the electromagnetic response of a plasmonic nanoparticle-spacer-plasmonic film system. The physical system consists of a spherical nanoparticle of a plasmonic material such as gold or silver over a plasmonic metal film and separated from the same by a dielectric spacer material. This paper presents a complete analytical solution of the Maxwell's equations, to determine the optical fields near the gold nanoparticle. It was found that the electromagnetic fields in between the plasmonic nanoparticle and the plasmonic film are extremely sensitive to the spacing between the nanoparticle and the film. This could enable the use of such a system for various sensing applications. The non-local nature of the plasmonic medium was also included in our analysis and it's effect on the resonances of the system was studied. The analytical solution was compared with an independent numerical method, the Finite Difference Time Domain (FDTD) method, to demonstrate the accuracy of the solution.

Two-dimensional skyrmions and other solitonic structures in confinement-frustrated chiral nematics.

We explore spatially localized solitonic configurations of a director field, generated using optical realignment and laser-induced heating, in frustrated chiral nematic liquid crystals confined between substrates with perpendicular surface anchoring. We demonstrate that, in addition to recently studied torons and Hopf-fibration solitonic structures (hopfions), one can generate a host of other axially symmetric stable and metastable director field configurations where local twist is matched to the surface boundary conditions through introduction of point defects and loops of singular and nonsingular disclinations. The experimentally demonstrated structures include the so-called "baby-skyrmions" in the form of double twist cylinders oriented perpendicular to the confining substrates where their double twist field configuration is matched to the perpendicular boundary conditions by loops of twist disclinations. We also generate complex textures with arbitrarily large skyrmion numbers. A simple back-of-the-envelope theoretical analysis based on free energy considerations and the nonpolar nature of chiral nematics provides insights into the long-term stability and diversity of these inter-related solitonic field configurations, including different types of torons, cholestric-finger loops, two-dimensional skyrmions, and more complex structures comprised of torons, hopfions, and various disclination loops that are experimentally observed in a confinement-frustrated chiral nematic system.

Evaluation of relationship between cranial base angle and maxillofacial morphology in Indian population: A cephalometric study.

OBJECTIVE: To investigate the role played by the cranial base flexure in influencing the sagittal and vertical position of the jaws in Indian population. MATERIALS AND METHODS: Lateral cephalograms of 108 subjects were divided into three categories (Group A: NSAr > 125°, Group B: NSAr-120°-125°, Group C: NSAr < 120°) according to value of NSAr. Measurement of eight angular (SNA, SNB, NPg-FH, ANB, NAPg, SN-GoGn, Y-Axis, ArGo-SN) and seven linear (N-S, S-Ar, Ar-N, Ar-Pt A, Ar-Gn, Wits appraisal, N- Pt A) variables were taken. RESULTS: Pearson correlation coefficient test was used to individually correlate angular and linear variables with NSAr for the whole sample as well as in individual group. Unpaired t-test was used to analyze the difference in the means of all the variables between the three groups. Significance was determined only when the confidence level was P < 0.05. Several parameters (SNB, NAPg, ANB, Y-Axis, GoGn-SN) showed significant positive correlation while others showed negative correlation (SNA, NPg-FH, N-S) with NSAr. CONCLUSIONS: This study show cranial base angle has a determinant role in influencing the mandibular position and it also affects both the mandibular plane angle and y-axis. Flattening of the cranial base angle caused a clockwise rotation of the mandible. The jaw relation tends to change from class III to class II, with progressive flattening of the cranial base and vice-versa.