Chemotherapy plus concurrent irreversible electroporation improved local tumor control in unresectable hilar cholangiocarcinoma compared with chemotherapy alone.

INTRODUCTION: Unresectable hilar cholangiocarcinoma (UHC) is a malignant tumor and has a poor prognosis. IRE is a novel non-thermal ablative therapy that causes cellular apoptosis via electrical impulses. To compare the curative effect for UHC, chemotherapy plus concurrent IRE and chemotherapy alone were set up. MATERIALS AND METHODS: From July 2015 to May 2019, 47 patients with UHC were analyzed to chemotherapy + IRE group (n = 23) or chemotherapy alone group (n = 24) in this study. Treatment response was assessed with computed tomography (CT) or magnetic resonance imaging (MRI) 1 month after treatment and every 3 months thereafter. Local tumor progression (LTP), time to LTP, overall survival (OS) and procedure-related complications were compared between the two groups. RESULTS: Chemotherapy plus concurrent IRE group showed a tendency toward a decreased rate of LTP (16.7% vs. 39.5%; p = 0.039) and an increased complete response rate (52.2% vs. 12.5%; p = 0.011) compared with chemotherapy alone group. Time to LTP was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (11.2 months vs. 4.2 months; p = 0.001). Median OS was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (19.6 months vs. 10.2 months; p = 0.001). CONCLUSIONS: Chemotherapy plus concurrent IRE improved local control and prolonged time to LTP and OS in patients with UHC.

Bio-inspired Photonic Masquerade with Perturbative Metasurfaces.

Camouflage is critical for many living organisms to survive in the natural world and has stimulated applications, such as optical cloaking and military affairs. However, most applications adopt crypsis-type camouflage that prevents the organisms from being detected by matching the environment, which is challenging to realize the large angle-of-view and broadband operation at optical frequencies. Here, as inspired by nature's system of masquerade, we demonstrate an optical masquerade, being detected but not recognized, with perturbative metasurfaces that could camouflage an object into another unrelated one under the oblique (±69°) illumination of visible light with an ∼160 nm bandwidth. Predicted by the perturbation theory, the dielectric metastructures encircling a pistol-shaped object have a thin layer of nanodisk array, which can suppress the electromagnetic resonances of nanomodes for mimicking the transmitted intensity and phase of the camouflaged object. We also exhibit that optical masquerade is an invasive, environment-independent, object-unlimited, and material-extendable camouflage, which might benefit optical security, anticounterfeiting, and encoding.

Design of mechanically-tunable photonic crystal split-beam nanocavity.

Photonic crystal split-beam nanocavities allow for ultra-sensitive optomechanical transductions but are degraded due to their relatively low optical quality factors. We have proposed and experimentally demonstrated a new type of one-dimensional photonic crystal split-beam nanocavity optimized for an ultra-high optical-quality factor. The design is based on the combination of the deterministic method and hill-climbing algorithm. The latter is the simplest and most straightforward method of the local search algorithm that provides the local maximum of the chosen quality factors. This split-beam nanocavity is made up of two mechanical uncoupled cantilever beams with Bragg mirrors patterned onto it and separated by a 75-nm air gap. Experimental results emphasize that the quality factor of the second-order TE mode can be as high as 1.99×10(4). Additionally, one beam of the device is actuated in the lateral direction with the aid of a NEMS actuator, and the quality factor maintains quite well even if there is a lateral offset up to 64 nm. Potentially promising applications, such as sensitive optomechanical torque sensor, local tuning of Fano resonance, all-optical-reconfigurable filters, etc., are foreseen.

Energy-efficient utilization of bipolar optical forces in nano-optomechanical cavities.

Nanoscale all-optical circuits driven by optical forces have broad applications in future communication, computation, and sensing systems. Because human society faces huge challenges of energy saving and emission reduction, it is very important to develop energy-efficient nano-optomechanical devices. Due to their high quality (Q) factors, resonance modes of cavities are capable of generating much larger forces than waveguide modes. Here we experimentally demonstrate the use of resonance modes of double-coupled one-dimensional photonic crystal cavities to generate bipolar optical forces. Attractive and repulsive forces of -6.2 nN and 1.9 nN were obtained with respective launching powers of 0.81 mW and 0.87 mW in the waveguide just before cavities. Supported by flexible nanosprings (spring constant 0.166 N/m), one cavity is pulled to (pushed away from) the other cavity by 37.1 nm (11.4 nm). The shifts of the selected resonance modes of the device are mechanically and thermally calibrated with an integrated nanoelectromechanical system actuator and a temperature-controlled testing platform respectively. Based on these experimentally-obtained relations, probe mode shifts due to the optomechanical effect are decoupled from those due to the thermo-optic effect. Actuated by the third-order even pump mode, the optomechanical shift of the second-order even probe mode is found to be about 2.5 times its thermal shift, indicating a highly efficient conversion of light energy to mechanical energy.

Tuning of split-ladder cavity by its intrinsic nano-deformation.

A wide-range split-ladder photonic crystal cavity which is tuned by changing its intrinsic gap width is designed and experimentally verified. Different from the coupled cavities that feature resonance splitting into symmetric and anti-symmetric modes, the single split-ladder cavity has only the symmetric modes of fundamental resonance and second-order resonance in its band gap. Finite-difference time-domain simulations demonstrate that bipolar resonance tuning (red shift and blue shift respectively) can be achieved by shrinking and expanding the cavity's gap, and that there is a linear relationship between the resonance shifts and changes in gap width. Simulations also show that the split-ladder cavity can possess a high Q-factor when the total number of air holes in the cavity is increased. Experimentally, comb drive actuator is used to control the extent of the cavity's gap and the variation of its displacements with applied voltage is calibrated with a scanning electron microscope. The measured wavelength of the second-order resonance shifts linearly towards blue with increase in gap width. The maximum blue shift is 17 nm, corresponding to a cavity gap increase of 26 nm with no obvious degradation of Q-factor.

An in-plane nano-mechanics approach to achieve reversible resonance control of photonic crystal nanocavities.

Control of photonic crystal resonances in conjunction with large spectral shifting is critical in achieving reconfigurable photonic crystal devices. We propose a simple approach to achieve nano-mechanical control of photonic crystal resonances within a compact integrated on-chip approach. Three different tip designs utilizing an in-plane nano-mechanical tuning approach are shown to achieve reversible and low-loss resonance control on a one-dimensional photonic crystal nanocavity. The proposed nano-mechanical approach driven by a sub-micron micro-electromechanical system integrated on low loss suspended feeding nanowire waveguide, achieved relatively large resonance spectral shifts of up to 18 nm at a driving voltage of 25 V. Such designs may potentially be used as tunable optical filters or switches.

Dynamic tuning of an optical resonator through MEMS-driven coupled photonic crystal nanocavities.

We present dynamic tuning of optical resonance using microelectromechanical systems (MEMS)-driven coupled photonic crystal (PhC) nanocavities. The device consists of an air-suspended one-dimensional PhC nanocavity coupled to input and output waveguides and a perturbing nanocavity attached to a submicrometer MEMS comb drive. Resonance tuning is achieved through varying the gap between the two coupled cavities. We demonstrate experimentally that resonance can be tuned up to 8nm with no significant deterioration in the Q factor. The proposed mechanism potentially enables a new platform of on-chip photonic devices that can achieve a large tuning range with low power and small footprint and may find useful applications in tunable optical/photonic devices.

Dynamic interactions between microbubbles in water.

The interaction between moving bubbles, vapor voids in liquid, can arguably represent the simplest dynamical system in continuum mechanics as only a liquid and its vapor phase are involved. Surprisingly, and perhaps because of the ephemeral nature of bubbles, there has been no direct measurement of the time-dependent force between colliding bubbles which probes the effects of surface deformations and hydrodynamic flow on length scales down to nanometers. Using ultrasonically generated microbubbles (approximately 100 microm size) that have been accurately positioned in an atomic force microscope, we have made direct measurements of the force between two bubbles in water under controlled collision conditions that are similar to Brownian particles in solution. The experimental results together with detailed modeling reveal the nature of hydrodynamic boundary conditions at the air/water interface, the importance of the coupling of hydrodynamic flow, attractive van der Waals-Lifshitz forces, and bubble deformation in determining the conditions and mechanisms that lead to bubble coalescence. The observed behavior differs from intuitions gained from previous studies conducted using rigid particles. These direct force measurements reveal no specific ion effects at high ionic strengths or any special role of thermal fluctuations in film thickness in triggering the onset of bubble coalescence.

Particulate templates and ordered liquid bridge networks in evaporative lithography.

We investigate the properties of latex particle templates required to optimize the development of ordered liquid bridge networks in evaporative lithography. These networks are key precursors in the assembly of solutions of conducting nanoparticles into large, optically transparent, and conducting microwire networks on substrates (Vakarelski, I. U.; Chan, D. Y. C.; Nonoguchi, T.; Shinto, H.; Higashitani, K. Phys. Rev. Lett., 2009, 102, 058303). An appropriate combination of heat treatment and oxygen plasma etching of a close-packed latex particle monolayer is shown to create open-spaced particle templates which facilitates the formation of ordered fully connected liquid bridge networks that are critical to the formation of ordered microwire networks. Similar results can also be achieved if non-close-packed latex particle templates with square or honeycomb geometries are used. The present results have important implications for the development of the particulate templates to control the morphology of functional microwire networks by evaporative lithography.

Hydrodynamic boundary conditions and dynamic forces between bubbles and surfaces.

Dynamic forces between a 50 microm radius bubble driven towards and from a mica plate using an atomic force microscope in electrolyte and in surfactant exhibit different hydrodynamic boundary conditions at the bubble surface. In added surfactant, the forces are consistent with the no-slip boundary condition at the mica and bubble surfaces. With no surfactant, a new boundary condition that accounts for the transport of trace surface impurities explains variations of dynamic forces at different speeds and provides a direct connection between dynamic forces and surface transport effects at the air-water interface.

Revealing biases inherent in recombination protocols.

BACKGROUND: The recombination of homologous genes is an effective protein engineering tool to evolve proteins. DNA shuffling by gene fragmentation and reassembly has dominated the literature since its first publication, but this fragmentation-based method is labor intensive. Recently, a fragmentation-free PCR based protocol has been published, termed recombination-dependent PCR, which is easy to perform. However, a detailed comparison of both methods is still missing. RESULTS: We developed different test systems to compare and reveal biases from DNA shuffling and recombination-dependent PCR (RD-PCR), a StEP-like recombination protocol. An assay based on the reactivation of beta-lactamase was developed to simulate the recombination of point mutations. Both protocols performed similarly here, with slight advantages for RD-PCR. However, clear differences in the performance of the recombination protocols were observed when applied to homologous genes of varying DNA identities. Most importantly, the recombination-dependent PCR showed a less pronounced bias of the crossovers in regions with high sequence identity. We discovered that template variations, including engineered terminal truncations, have significant influence on the position of the crossovers in the recombination-dependent PCR. In comparison, DNA shuffling can produce higher crossover numbers, while the recombination-dependent PCR frequently results in one crossover. Lastly, DNA shuffling and recombination-dependent PCR both produce counter-productive variants such as parental sequences and have chimeras that are over-represented in a library, respectively. Lastly, only RD-PCR yielded chimeras in the low homology situation of GFP/mRFP (45% DNA identity level). CONCLUSION: By comparing different recombination scenarios, this study expands on existing recombination knowledge and sheds new light on known biases, which should improve library-creation efforts. It could be shown that the recombination-dependent PCR is an easy to perform alternative to DNA shuffling.

Improvement of a CrtO-type of beta-carotene ketolase for canthaxanthin production in Methylomonas sp.

Two types of non-homologous beta-carotene ketolases (CrtW and CrtO) were previously described. We report improvement of a CrtO-type of beta-carotene ketolase for canthaxanthin production in a methylotrophic bacterium, Methylomonas sp. 16a, which could use the C1 substrate (methane or methanol) as sole carbon and energy source. The crtO gene from Rhodococcus erythropolis was improved for canthaxanthin production in an E. coli strain engineered to produce high titer carotenoids by error-prone PCR mutagenesis followed by in vitro recombination. The best mutants from protein engineering could produce approximately 90% of total carotenoids as canthaxanthin in the high titer E. coli strain compared to approximately 20% canthaxanthin produced by the starting gene. Canthaxanthin production in Methylomonas was also significantly improved to approximately 50% of total carotenoids by the mutant genes. Further improvement of canthaxanthin production to approximately 93% in Methylomonas was achieved by increased expression of the best mutant gene. Some mutations were found in many of the improved genes, suggesting that these sites, and possibly the regions around these sites, were important for improving the crtO's activity for canthaxanthin production.