Net Amplification Research Articles

Stimulated intermodal Brillouin scattering in a hybrid photonic-phononic silicon waveguide

On-chip stimulated Brillouin scattering (SBS) has attracted extensive attention by introducing acousto-optic coupling interactions in all-optical signal processing systems. In this article, we demonstrate stimulated intermodal Brillouin scattering (SIMBS) through a hybrid photonic-phononic silicon waveguide on the silicon-on-insulator (SOI) platform. The designed photonic-phononic waveguide can independently control the optical and acoustic fields by introducing the ridge waveguide as a line defect into the honeycomb lattice phononic crystal slab. Small-signal Stokes gain of 0.7 dB is achieved in a 1-cm long straight waveguide device with an on-chip pump power of 42.5 mW. Positive net Brillouin amplification is also expected by effectively reducing the linear loss. Our proposed device offers a potential approach to implementing Brillouin amplifiers, nonreciprocal devices, and signal processing in planar photonic integrated circuits.

Generation of intense dissipation in high Reynolds number turbulence

Intense fluctuations of energy dissipation rate in turbulent flows result from the self-amplification of strain rate via a quadratic nonlinearity, with contributions from vorticity (via the vortex stretching mechanism) and pressure-Hessian—which are analysed here using direct numerical simulations of isotropic turbulence on up to grid points, and Taylor-scale Reynolds numbers in the range 140–1300. We extract the statistics involved in amplification of strain and condition them on the magnitude of strain. We find that strain is self-amplified by the quadratic nonlinearity, and depleted via vortex stretching, whereas pressure-Hessian acts to redistribute strain fluctuations towards the mean-field and hence depletes intense strain. Analysing the intense fluctuations of strain in terms of its eigenvalues reveals that the net amplification is solely produced by the third eigenvalue, resulting in strong compressive action. By contrast, the self-amplification acts to deplete the other two eigenvalues, whereas vortex stretching acts to amplify them, with both effects cancelling each other almost perfectly. The effect of the pressure-Hessian for each eigenvalue is qualitatively similar to that of vortex stretching, but significantly weaker in magnitude. Our results conform with the familiar notion that intense strain is organized in sheet-like structures, which are in the vicinity of, but never overlap with tube-like regions of intense vorticity due to fundamental differences in their amplifying mechanisms.This article is part of the theme issue ‘Scaling the turbulence edifice (part 1)’.

Comprehensive Activation Profiling of the Tabelecleucel Library, an Off-the-Shelf, Allogeneic EBV-Specific T-Cell Therapy

Background: Tabelecleucel (Tab-cel) is an investigational, off-the-shelf, allogenic Epstein-Barr virus (EBV)-specific T-cell immunotherapy. Tab-cel has shown clinical activity in patients with EBV + post-transplant lymphoproliferative disease (PTLD). Previously we have shown that the process for generating tab-cel from healthy donors results in a net amplification of EBV-target responsive T-cell clonality, and that upon activation, tab-cel demonstrates polyfunctionality associated with the secretion of effector and chemoattractive cytokines.Objective: We aim to comprehensively profile tab-cel through immunophenotype, TCR repertoire by analyzing overall repertoire overlap across lots, and TCR sequence homology (GLIPH 2.0 algorithm), cytokine polyfunctionality (PF), and differential gene expression patterns (GEP) between resting and TCR-MHC-driven EBV antigen stimulation states to replicate intrinsic effector responses associated with EBV + disease engagement.Methods: Immunophenotyping was performed using targeted FACS activation profiling (CD25/CD69), and 40-plex CyTOF. PF response and cytokine profiles were evaluated using the IsoLight single-cell PF strength assay. TCR repertoires were assessed using TCRβ immunoSEQ, and the GLIPH 2.0 algorithm was utilized to cluster TCRs that are predicted to bind the same MHC-restricted peptide antigen. GEP were evaluated using a custom Nanostring panel consisting of 333 T-cell lineage gene targets.Results: Baseline control activation levels of 7.9±1.3% increased specifically to 54.3±3.7% post-activation with EBV + targets (Figure 1A). Baseline PF was 0.54±0.14%, and upon EBV-specific activation, product cells demonstrated an average PF of 12.1±1.5%, demonstrating a 22.7-fold average increase (Figure 1B).The cytokine profile for activated tab-cel lots is primarily comprised of effector and chemoattractive cytokines including IFNγ and MIP1β. Baseline TCR repertoires of the initial donor peripheral T-cells are highly diverse; however, the tab-cel manufacturing process effectively amplified and enriched for EBV-specific TCRs that correspond back to a starting frequency of 2.6±0.58% of the initial donor TCR repertoire (Figure 1C). Notably, cross comparison of tab-cel-enriched TCRs against publicly available databases (VDJdb, McPas-TCR) identified previously curated EBV-specific TCRβ sequences as a component of the expanded repertoire. Additionally, using the GLIPH 2.0 clustering algorithm we were able to identify previously unannotated TCR sequences that clustered with known EBV-specific TCRβ sequences. The tab-cel post-activation GEP revealed associations with T-cell activation and polyfunctionality. The CD4/CD8 composition of a subset of tab-cel lots was analyzed: the average CD4:CD8 ratio of 0.25, with an average of CD8+ T-cells comprising 73% of the product. An extended immunophenotyping by CyTOF is currently being completed and will be reported at the time of presentation.Conclusions: In this expanded analysis we again demonstrate that the process for generating tab-cel from healthy donors enriches for known EBV-specific clones and results in a net amplification of EBV-target responsive T-cell clonality. Additionally, utilization of the GLIPH 2.0 clustering algorithm has led to the identification of novel putative EBV-specific TCR sequences that are enriched through the tab-cel manufacturing process. Upon activation, tab-cel exhibits a robust multifactorial activation signaling and demonstrates PF associated with secretion of effector and chemoattractive cytokines. Gene expression profiling of activated tab-cel lots highlights a conserved activation gene signature that is associated with post-activation PF. Lastly, these above analyses are being leveraged to perform correlation studies of immunophenotyped to post-activation PF, TCR repertoire characteristics, and GEP. These data support that the process for generating tab-cel from healthy donor PBMCs leads to the enrichment for EBV-specific T-cell clones that are capable of becoming activated upon stimulation with consistent final product characteristics. [Display omitted] DisclosuresBenoun: Atara Biotherapeutics: Current Employment. Ruiz: Atara Biotherapeutics: Current Employment. Widmann: Atara Biotherapeutics: Current Employment. Jehng: Atara Biotherapeutics: Current Employment. Spindler: Atara Biotherapeutics: Current Employment. Abraham: Atara Biotherapeutics: Current Employment. Minne: Atara Biotherapeutics: Consultancy. Tracy: Atara Biotherapeutics: Current Employment. Munson: Atara Biotherapeutics: Current Employment. Thota: Atara Biotherapeutics: Current Employment. Wang: Atara Biotherapeutics: Current Employment. Chuan: Atara Biotherapeutics: Current Employment. Yedwabnick: Atara Biotherapeutics: Current Employment. Dubovsky: Atara Biotherapeutics: Current Employment.

Scaling of Small-scale Dynamo Properties in the Rayleigh–Taylor Instability

Abstract We derive scaling relations based on freefall and isotropy assumptions for the kinematic small-scale dynamo growth rate and amplification factor over the course of the mixing, saturation, and decay phases of the Rayleigh–Taylor instability (RTI) in a fully ionized plasma. The scaling relations are tested using sets of three-dimensional, visco-resistive MHD simulations of the RTI. They are found to hold in the saturation phase, but exhibit discrepancies during the mixing and decay phases, suggesting a need to relax either the freefall or isotropy assumptions. Application of the scaling relations allows for quantitative prediction of the net amplification of magnetic energy in the kinematic dynamo phase and therefore a determination of whether the magnetic energy either remains sub-equipartition at all velocity scales or reaches equipartition with at least some scales of the turbulent kinetic energy in laboratory and astrophysical scenarios. As an example, we consider the dynamo in RTI-unstable regions of the outer envelope of a binary neutron star merger, and predict that the kinematic regime of the small-scale dynamo ends on the timescale of nanoseconds and then reaches saturation on a timescale of microseconds, which are both fast compared to the millisecond relaxation time of the post-merger.

Meta-Prediction Models for Bullwhip Effect Prediction of a Supply Chain Using Regression Analysis

In this study, the main factors that can cause the bullwhip effect and stock amplification are investigated using a simulation-based optimization approach and regression analysis. A two-echelon supply chain with uncertain customer demand and delivery lead time operating with the periodic-review reorder cycle policy is studied. The parameters of smoothing inventory replenishment and forecasting methods are required. These parameters are optimized in terms of minimizing the Total Stage Variance Ratios (TSVRs) of both echelons. The results show that even though all factors of interest have an impact on the bullwhip effect, using smoothing proportional controllers can reduce TSVRs (the sum of the order varaince ratio and net stock amplification). The meta-prediction models can effectively help predict the amount of the bullwhip effect of a chain under various situations with an average MAPE of less than 11%. The results can assist decision makers in the management of a supply chain to realize, benchmark with the optimal results, and reduce the TSVRs under an uncertain environment.

Demonstration of Forward Brillouin Gain in a Hybrid Photonic–Phononic Silicon Waveguide

Silicon-based stimulated Brillouin scattering (SBS) promotes the on-chip all-optical signal processing network by interfacing silicon photonic and phononic technologies. Controllable and strong Brillouin coupling in silicon is a key requirement for this purpose. Here, we demonstrate traveling-wave forward SBS and Brillouin gain through a class of hybrid photonic-phononic silicon waveguides on the silicon-on-insulator (SOI) platform. This design combines the advantages of a silicon ridge waveguide and phononic crystal slab, allowing the independent control on the confined optical and acoustic modes. The strong and tailorable Brillouin nonlinearity is demonstrated via the heterodyne four-wave mixing spectroscopy. Three-tone gain experiment reveals a small-signal Stokes gain of 0.9 dB in a 1.085 cm length straight waveguide device at moderate pump power. The limiting factors and further improvements of net Brillouin amplification in our system are also discussed. This design can also be applied to the intermodal SBS as well as other silicon-based material platforms, and thus it offers the pathway toward on-chip microwave photonic filters, Brillouin amplifiers, and nonreciprocal devices.

High-gain waveguide amplifiers in Si3N4 technology via double-layer monolithic integration

Silicon nitride ( Si 3 N 4 ) - on - SiO 2 attracts increasing interest in integrated photonics owing to its low propagation loss and wide transparency window, extending from ∼ 400 nm to 2350 nm. Scalable integration of active devices such as amplifiers and lasers on the Si 3 N 4 platform will enable applications requiring optical gain and a much-needed alternative to hybrid integration, which suffers from high cost and lack of high-volume manufacturability. We demonstrate a high-gain optical amplifier in Al 2 O 3 : Er 3 + monolithically integrated on the Si 3 N 4 platform using a double photonic layer approach. The device exhibits a net Si 3 N 4 - to - Si 3 N 4 gain of 18.1 ± 0.9 dB at 1532 nm, and a broadband gain operation over 70 nm covering wavelengths in the S-, C- and L-bands. This work shows that rare-earth-ion-doped materials and in particular, rare-earth-ion-doped Al 2 O 3 , can provide very high net amplification for the Si 3 N 4 platform, paving the way to the development of different active devices monolithically integrated in this passive platform.

Homologous Quorum Sensing Regulatory Circuit: A Dual-Input Genetic Controller for Modulating Quorum Sensing-Mediated Protein Expression in E. coli.

We developed a hybrid synthetic circuit that co-opts the genetic regulation of the native bacterial quorum sensing autoinducer-2 and imposes an extra external controller for maintaining tightly controlled gene expression. This dual-input genetic controller was mathematically modeled and, by design, can be operated in three modes: a constitutive mode that enables consistent and high levels of expression; a tightly repressed mode in which there is very little background expression; and an inducible mode in which concentrations of two signals (arabinose and autoinducer-2) determine the net amplification of the gene(s)-of-interest. We demonstrate the utility of the circuit for the controlled expression of human granulocyte macrophage colony stimulating factor in an engineered probiotic E.coli. This dual-input genetic controller is the first homologous AI-2 quorum sensing circuit that has the ability to be operated in three different modes. We believe it has the potential for wide-ranging biotechnological applications due its versatile features.

Analysis of Variance Amplification and Service Level in a Supply Chain with Correlated Demand

The bullwhip effect reflects the variance amplification of demand as they are moving upstream in a supply chain, and leading to the distortion of demand information that hinders supply chain performance sustainability. Extensive research has been undertaken to model, measure, and analyze the bullwhip effect while assuming stationary independent and identically distributed (i.i.d) demand, employing the classical order-up-to (OUT) policy and allowing return orders. On the contrary, correlated demand where a period’s demand is related to previous periods’ demands is evident in several real-life situations, such as demand patterns that exhibit trends or seasonality. This paper assumes correlated demand and aims to investigate the order variance ratio (OVR), net stock amplification ratio (NSA), and average fill rate/service level (AFR). Moreover, the impact of correlated demand on the supply chain performance under various operational parameters, such as lead-time, forecasting parameter, and ordering policy parameters, is analyzed. A simulation modeling approach is adopted to analyze the response of a single-echelon supply chain model that restricts return orders and faces a first order autoregressive demand process AR(1). A generalized order-up-to policy that allows order smoothing through the proper tuning of its smoothing parameters is applied. The characterization results confirm that the correlated demand affects the three performance measures and interacts with the operating conditions. The results also indicate that the generalized OUT inventory policy should be adopted with the correlated demand, as its smoothing parameters can be adapted to utilize the demand characteristics such that OVR and NSA can be reduced without affecting the service level (AFR), implying sustainable supply chain operations. Furthermore, the results of a factorial design have confirmed that the ordering policy parameters and their interactions have the largest impact on the three performance measures. Based on the above characterization, the paper provides management with means to sustain good performance of a supply chain whenever a correlated demand pattern is realized through selecting the control parameters that decrease the bullwhip effect.

Design of Partially Suspended Silicon Nitride Slot Waveguides for Efficient Forward Stimulated Brillouin Scattering

We design a partially suspended silicon nitride (Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> ) slot waveguide on silica to realize efficient on-chip forward stimulated Brillouin scattering (FSBS). The slot waveguide can intensify radiation pressure close to the slot and simultaneously confine both optical and acoustic modes, resulting in an enhanced FSBS gain on the order of 300 W <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> . The acoustic radiation loss is significantly suppressed due to the strong acoustic coupling in the narrow slot waveguides. We analyze the impacts of structural parameters on the SBS properties, which produces the optimal parameters for maximum SBS gain. Based on the nonlinear coupled-mode equations, we compare the performance of Stokes amplification between the Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> slot waveguides and the silicon nanowires. Simulation results indicate that the Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> slot waveguides with low linear loss can offer a larger net Stokes amplification than silicon waveguides under moderate pump power. Such approach enables efficient on-chip SBS devices in CMOS-compatible Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> platform.

Deconstructing the Impact of Malaria Vector Diversity on Disease Risk.

AbstractRecent years have seen significant progress in understanding the impact of host community assemblage on disease risk, yet diversity in disease vectors has rarely been investigated. Using published malaria and mosquito surveys from Kenya, we analyzed the relationship between malaria prevalence and multiple axes of mosquito diversity: abundance, species richness, and composition. We found a net amplification of malaria prevalence by vector species richness, a result of a strong direct positive association between richness and prevalence alongside a weak indirect negative association between the two, mediated through mosquito community composition. One plausible explanation of these patterns is species niche complementarity, whereby less competent vector species contribute to disease transmission by filling spatial or temporal gaps in transmission left by dominant vectors. A greater understanding of vector community assemblage and function, as well as any interactions between host and vector biodiversity, could offer insights to both fundamental and applied ecology.

Multi-objective optimisation framework of genetic programming for investigation of bullwhip effect and net stock amplification for three-stage supply chain systems

In this work a multi-objective optimisation framework of genetic programming (GP) in the modelling of bullwhip effect and NSA for centralised and decentralised supply chain systems has been proposed. The individual and interactive effect of these four input factors has been investigated on bullwhip effect and NSA by adapting the parametric and sensitivity approach on the formulated models. The appropriate settings of dominant input factors (batch ordering and demand signal processing for a decentralised chain, demand signal processing and rationing shortage gaming for a centralised chain) are suggested to optimise the bullwhip effect and NSA of three-stage supply chain simultaneously. The implications and advantages of proposed optimisation framework will be useful for business practitioners to monitor and supervise the sudden demand amplification that generally faced by them in the supply chains.

Multi-objective optimisation framework of genetic programming for investigation of bullwhip effect and net stock amplification for three-stage supply chain systems

Multi-objective optimisation framework of genetic programming for investigation of bullwhip effect and net stock amplification for three-stage supply chain systems

Large on-chip Brillouin net amplification in silicon-based nano-photonics

Recent developments in on-chip forward Brillouin scattering open up potential applications such as RF photonic signal processing, on-chip Brillouin amplification, and on-chip Brillouin lasers. The stimulated Brillouin scattering gain coefficients become significant with a small optical mode area, and the Brillouin net amplification has been believed to be strong with a small mode area, too. However, here, we present a theoretical study of higher net amplification with a large optical mode area than that with a small mode area and explain this counter-intuitive phenomenon by examining the contribution of various optical forces to Brillouin gain coefficients for various optical waveguide dimensions. The simulation results show that a waveguide with large optical waveguide dimensions can yield significant net amplification by high Brillouin gain coefficients and low optical losses at high pump power even if the Brillouin gain coefficients are lower than that with a small waveguide dimension. Therefore, it is necessary to optimize the optical waveguide dimensions to achieve maximum net amplification for the development of Brillouin lasers and amplifiers in silicon-based nanophotonics.

A self-amplifying dielectric-elastomer-amplified piezoelectric for motion-based energy harvesting

The dielectric elastomer generator is a stretchable generator that converts low-frequency motions into electrical output, with excellent impedance matching capabilities. However, the dielectric elastomer requires an external high-voltage priming source to initialize its operation. We previously proposed a piezoelectric generator as the priming source, and demonstrated a net amplification of specific output energy of 1.8 times by the dielectric elastomer generator, as compared with that of the piezoelectric working in isolation. We termed our prototype the dielectric-elastomer-amplified piezoelectric (DEAmP). In this version, we introduce a self-priming circuit that will progressively charge up the dielectric elastomer generator to a much higher potential, thereby allowing the system to approach its optimized operating voltage. We term this the DEAmPx generator, with the letter “x” denoting progressive voltage/charge amplification by the self-priming circuit. The DEAmPx attained an output voltage of about 2000 V in 18 cycles and generates a dielectric elastomer generator–specific energy output of 3.1 mJ/g per cycle—19 times higher than that of the piezoelectric generator working in isolation. The system-specific energy output of DEAmPx is 0.49 mJ/g, with just a single layer of elastomer film. With this significantly larger output, we demonstrate the capability of a single-layer DEAmPx to power dielectric elastomer actuators.

State factor network analysis of ecosystem response to climate change

Case studies of ecosystem responses to changing climates are necessary in understanding and adapting to these changes. However, more general conceptual frameworks are also needed to contextualize and synthesize case studies, and to provide guidelines for assessment and prediction. This study analyzes a network model of ecological and soil state factor interrelationships to address issues such as sensitivity, resilience, and complexity of climate-driven terrestrial ecosystem changes. A factorial ecosystem model is analyzed using techniques from algebraic graph theory. Results show high values for spectral radius, graph energy, and algebraic connectivity. These indicate complexity, dynamical instability, active reverberating feedbacks, and high synchronization. Implications are that climate effects on ecosystems will be complicated, complex, and difficult to predict. We should be prepared for surprises in the form of unanticipated pathways and outcomes. The inherent nature of ecosystem interconnectivity indicated by the state factor model also suggests that when simulation models and change assessments do turn out to be wrong, it does not necessarily mean the underlying scientific understandings, data, or assumptions are wrong, as sensitivity to relatively minor variations and disturbances is high, and complexity and low predictability are inherent. Ecosystem reactions to climate (and other, often contemporaneous) changes will reverberate through the ecosystem. Both filtering and amplification may occur, but net amplification is indicated by the graph analysis. Ecosystem responses are integrated system responses–state factors will respond as a single integrated unit, not as a collection or sequence of individual responses.

Resonantly enhanced nonreciprocal silicon Brillouin amplifier

The ability to amplify light within silicon waveguides is central to the development of high-performance silicon photonic device technologies. To this end, the large optical nonlinearities made possible through stimulated Brillouin scattering offer a promising avenue for power-efficient all-silicon amplifiers, with recent demonstrations producing several dB of net amplification. However, scaling the degree of amplification to technologically compelling levels (>10 dB), necessary for everything from filtering to small signal detection, remains an important goal. Here, we significantly enhance the Brillouin amplification process by harnessing an inter-modal Brillouin interaction within a multi-spatial-mode silicon racetrack resonator. Using this approach, we demonstrate more than 20 dB of net Brillouin amplification in silicon, advancing state-of-the-art performance by a factor of 30. This degree of amplification is achieved with modest (~15 mW) continuous-wave pump powers and produces low out-of-band noise. Moreover, we show that this same system behaves as a unidirectional amplifier, providing more than 28 dB of optical nonreciprocity without insertion loss in an all-silicon platform. Building on these results, this device concept opens the door to new types of all-silicon injection-locked Brillouin lasers, high-performance photonic filters, and waveguide-compatible distributed optomechanical phenomena.

A high energy dielectric-elastomer-amplified piezoelectric (DEAmP) to harvest low frequency motions

A dielectric elastomer generator (DEG) needs a high voltage priming source and large operating strains to produce a specific energy output in excess of 1 J/kg. For small-scale energy harvesting applications like a heel-strike generator, there is limited space. Providing such a priming source and a large amount of strain in a constrained space is challenging. To address this challenge, we present a dielectric-elastomer-amplified piezoelectric (DEAmP) generator. The piezoelectric generator charges the DEG and the DEG amplifies the voltage of the charges placed on it. Using a piezoelectric as a priming source makes our system much more compact and autonomous than others that use batteries and amplifiers as priming sources. From analysis, we define conditions of operation where there is a net amplification by the DEG and identify optimal conditions where up to 250 times in amplification of output energy could be produced. To produce large deformation on the DE within a constrained space, we propose the ripple mode of deformation. A simple analytical model and a design plot of the ripple mode was presented. Following our analyses, we construct a 3D-printed prototype that would demonstrate gain in energy harvested from a generic source of motion, reminiscent to that of a human footfall. We showed that the piezoelectric generator used in our experiment singly produces a specific energy output of 0.16 mJ/g, whereas the DEAmP generator yields 0.29 mJ/g. We showed the capability of a DEAmP to deliver an amplified output as compared to a standalone piezoelectric, even when harvesting low frequency motions. We discuss several strategies to further enhance the performance of a DEAmP.

Efficient long-term amplification of hepatitis B virus isolates after infection of slow proliferating HepG2-NTCP cells

As hepatitis B virus (HBV) spreads through the infected liver it is simultaneously secreted into the blood. HBV-susceptible in vitro infection models do not efficiently amplify viral progeny or support cell-to-cell spread. We sought to establish a cell culture system for the amplification of infectious HBV from clinical specimens. An HBV-susceptible sodium-taurocholate cotransporting polypeptide-overexpressing HepG2 cell clone (HepG2-NTCPsec+) producing high titers of infectious progeny was selected. Secreted HBV progeny were characterized by native gel electrophoresis and electron microscopy. Comparative RNA-seq transcriptomics was performed to quantify the expression of host proviral and restriction factors. Viral spread routes were evaluated using HBV entry- or replication inhibitors, visualization of viral cell-to-cell spread in reporter cells, and nearest neighbor infection determination. Amplification kinetics of HBV genotypes B-D were analyzed. Infected HepG2-NTCPsec+ secreted high levels of large HBV surface protein-enveloped infectious HBV progeny with typical appearance under electron microscopy. RNA-seq transcriptomics revealed that HBV does not induce significant gene expression changes in HepG2-NTCPsec+, however, transcription factors favoring HBV amplification were more strongly expressed than in less permissive HepG2-NTCPsec-. Upon inoculation with HBV-containing patient sera, rates of infected cells increased from 10% initially to 70% by viral spread to adjacent cells, and viral progeny and antigens were efficiently secreted. HepG2-NTCPsec+ supported up to 1,300-fold net amplification of HBV genomes depending on the source of virus. Viral spread and amplification were abolished by entry and replication inhibitors; viral rebound was observed after inhibitor discontinuation. The novel HepG2-NTCPsec+ cells efficiently support the complete HBV life cycle, long-term viral spread and amplification of HBV derived from patients or cell culture, resembling relevant features of HBV-infected patients. Currently available laboratory systems are unable to reproduce the dynamics of hepatitis B virus (HBV) spread through the infected liver and release into the blood. We developed a slowly dividing liver-derived cell line which multiplies infectious viral particles upon inoculation with patient- or cell culture-derived HBV. This new infection model can improve therapy by measuring, in advance, the sensitivity of a patient's HBV strain to specific antiviral drugs.

Femtosecond Thin-Film Laser Amplifiers Using Chirped Gratings.

Ultrafast injection-locked amplification is achieved by sending femtosecond supercontinuum pulses into a polymeric thin film coated on a distributed feedback (DFB) microcavity consisting of chirped gratings. The spatial variation of the grating period led to the resonance of the DFB microcavity at different wavelengths for injection at different locations. This enables convenient and continuous tuning of the amplification spectrum by displacing the grating structures. The large area of the grating structures enabled large tuning range. The amplified spectrum can be continuously tuned from 545 to 580 nm through sliding the grating structures by about 3.5 mm. Sub-1 ps lifetime has been measured for the amplification process with a net amplification factor as large as 33. Injection locking enabled high-quality control of the divergence and transverse mode of the output laser beam.