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The success of laser-foil-printing (LFP) additive manufacturing depends critically on the laser welding of sheet metals onto the substrate or the previous layer during the part fabrication process. The welding can be generally categorized into two modes: conduction mode and keyhole mode. In this study, 304L stainless steel parts fabricated by the LFP process using the two laser welding modes are compared. The porosity, microstructure, and tensile properties of the fabricated parts in these two modes are measured and compared in the laser scanning direction (X) and part building direction (Z). The parts fabricated in the conduction mode have a higher density than those fabricated in the keyhole mode. On the tensile properties, both yield strength (YS) and ultimate tensile strength (UTS) have insignificant differences statistically based on the ANOVA analysis between the tensile specimens fabricated with the two welding modes by the LFP process. However, the conduction-mode parts have higher elongation than the keyhole-mode parts in both the X and Z directions, and the difference is especially significant in the Z direction. By using the electron backscattered diffraction (EBSD), it was found that the much higher ductility for the conduction-mode parts in the Z-axis direction is mainly due to the distinct grain boundary interface density in the Z-axis direction between the two welding modes.

We present a novel photonic integrated circuit (PIC) that monolithically integrates a racetrack colliding-pulse mode-locked laser with a pulse-picking electro-absorption modulator and a semiconductor optical amplifier on Indium Phosphide. We present detailed characterization of this PIC that includes optical pulse characterization, phase noise and long term stability under passive and hybrid mode-locking conditions. Allan deviation measurements made on the optical pulse train from the PIC show a fractional frequency instability of $8\times 10 ^{-11}$ at 1 second and follow a 1/ $\tau $ trend. We also demonstrate repetition rate reduction from ~10 GHz to ~500 MHz with an extinction ratio of ~14.65 dB using an on-chip pulse-picking electro-absorption modulator.

Silicon photonics is a rapidly maturing platform for optical communication and sensing. As systems leveraging silicon photonics have grown in size and complexity, so too has the demand for high performance silicon photonics components. In order to meet these demands, we propose a hierarchical approach to design and optimization of silicon photonics components. Our approach applies simple physical analysis to choose an effective starting geometry for a two-step gradient-based shape optimization. This optimization employs carefully chosen geometrical constraints in order to consistently produce robust, high performance devices which satisfy practical fabrication constraints of deep UV lithography. In order to demonstrate the versatility of method, we optimize a 3 dB coupler which achieves better than 0.04 dB excess loss over the O-band, a four port 3-dB coupler which achieves better than 0.41 dB excess loss and near 50:50 splitting over the O-band, and a fabrication-tolerant waveguide crossing which achieves better than 0.075 dB insertion loss over the O-band even when subject to $\pm \text{10}$ % silicon thickness variations. These results pave the way for high efficiency silicon photonic component libraries.

We report on a co-planar light-actuated digital microfluidics device that features a metal mesh grid integrated on the device surface to allow droplets to be exposed from above. We discuss a theoretical circuit model for our co-planar optoelectrowetting (OEW) design that allows for the optimization of droplet actuation while maintaining reliable droplet movement. Basic droplet manipulations such as merging and parallel actuation of droplets are achieved at speeds of up to 4.5 cm / s. The co-planar OEW device design benefits from having an open top design that allows for a wider range of system integration configurations than previous generations of OEW devices. A droplet-on-demand dispensing system from above is integrated with the co-planar OEW device to demonstrate the versatility of this optofluidic platform. The ability to inject, collect, and position individual droplets to form large-scale droplet arrays of up to 20 × 20 is achieved.

Synthetic biology has potential spaceflight applications yet few if any studies have attempted to translate Earth-based synthetic biology tools into spaceflight. An exogenously inducible biological circuit for protein production in Arabidopsis thaliana, pX7-AtPDSi (Guo et al. 2003), was flown to ISS and functionally investigated. Seedlings were grown in a custom built 1.25 U plant greenhouse. Images recorded during the experiment show that leaves of pX7-AtPDSi seedlings photobleached as designed while wild type Col-0 leaves did not, which reveals that the synthetic circuit led to protein production during spaceflight. Polymerase chain reaction analysis post-flight also confirms that the Cre/LoxP (recombination system) portions of the circuit were functional in spaceflight. The subcomponents of the biological circuit, estrogen-responsive transcription factor XVE, Cre/LoxP DNA recombination system, and RNAi post-transcriptional gene silencing system now have flight heritage and can be incorporated in future designs for space applications. To facilitate future plant studies in space, the full payload design and manufacturing files are made available.

Obesity is a major risk factor for hypertension. Although the renin-angiotensin system (RAS) contributes to the sex difference of blood pressure (BP) control, whether the prorenin receptor (PRR) and its soluble form (sPRR) play a role in the sexual dimorphism of BP is not clear. We previously demonstrated that, in high fat (HF)-fed male C57BL/6 mice, the infusion of mouse recombinant sPRR increased systolic blood pressure (SBP) by the sympatho-excitatory effects of leptin on BP. Therefore, in the present study, we aim to address whether mouse recombinant sPRR influences the BP in HF-fed female mice. To test this hypothesis, C57BL/6 female mice were fed a HF diet for 32 weeks and were implanted with radiotelemetry transmitter. After 24 weeks of high fat feeding, female mice (5-6/group) were implanted with osmotic pumps and infused with either saline (veh) or sPRR for 3 to 4 weeks. In contrast to male mice, the infusion of sPRR (30 μg/kg/day) did not change significantly the SBP (24hSBP; veh: 135 ± 7; sPRR: 134 ± 4 mmHg; P>0.05) and the baroreflex sensitivity. The decrease in BP mediated by chlorisondamine treatment was not significantly different between female mice infused with vehicle or sPRR (ΔSBP; veh: -11 ± 9; sPRR: -16 ± 7 mmHg; P>0.05). In addition, sPRR infusion did not affect the bradycardic or tachycardic responses after propranolol or atropine treatment respectively. Moreover, the decrease of SBP induced by losartan was similar in mice infused with vehicle or sPRR (ΔSBP; veh: -9 ± 4; sPRR: -10 ± 3 mmHg; P>0.05). Similar results were obtained using higher dose of sPRR (60 μg/kg/day). In female mice, sPRR infusion did not increase significantly the body weight (veh: 32.7 ± 2.5 g; sPRR: 35.8 ± 4.2 g; P>0.05), the white adipose tissue weight (WAT; veh: 3.0 ± 0.7g; sPRR: 3.7 ± 1.6 g; P>0.05) or circulating leptin levels (veh: 12.0 ± 7.6 ng/ml; sPRR: 15.5 ± 9.5 ng/ml; P>0.05). In conclusion, in contrast to male, female mice are protected from sPRR-induced increase in BP. sPRR did not increase circulating leptin suggesting that sPRR-induced leptin increase is regulated in a sex-dependent manner. Other pathways could participate to the protection against sPRR-induced increase in BP in female mice such as the vasodilator arm of the RAS and/or the hormonal status of the female mice.

PURPOSE Nonadherence to aromatase inhibitors (AIs) for breast cancer is common and increases the risk of recurrence. Text messaging increases adherence to medications for chronic conditions. METHODS We conducted a randomized clinical trial of text messaging (TM) versus no text messaging (No-TM) at 40 sites in the United States. Eligible patients were postmenopausal women with early-stage breast cancer taking an AI for > 30 days with a planned duration of ≥ 36 months. Test messages were sent twice a week over 36 months. Content themes focused on overcoming barriers to medication adherence and included cues to action, statements related to medication efficacy, and reinforcements of the recommendation to take AIs. Both groups were assessed every 3 months. The primary outcome was time to adherence failure (AF), where AF was defined as urine AI metabolite assay results satisfying one of the following: < 10 ng/mL, undetectable, or no submitted specimen. A stratified log-rank test was conducted. Multiple sensitivity analyses were performed. RESULTS In total, 724 patients were registered between May 2012 and September 2013, among whom,702 patients (348 in the text-messaging arm and 354 in the no–text-messaging arm) were eligible at baseline. Observed adherence at 36 months was 55.5% for TM and 55.4% for No-TM. The primary analysis showed no difference in time to AF by arm (3-year AF: 81.9% TM v 85.6% No-TM; HR, 0.89 [95% CI, 0.76 to 1.05]; P = .18). Multiple time to AF sensitivity analyses showed similar nonsignificant results. Three-year self-reported time to AF (10.4% v 10.3%; HR, 1.16 [95% CI, 0.69 to 1.98]; P = .57) and site-reported time to AF (21.9% v 18.9%; HR, 1.31 [95% CI, 0.86 to 2.01]; P = .21) also did not differ by arm. CONCLUSION To our knowledge, this was the first large, long-term, randomized trial of an intervention directed at improving AI adherence. We found high rates of AI AF. Twice-weekly text reminders did not improve adherence to AIs. Improving long-term adherence will likely require personalized and sustained behavioral interventions.

Transition metal dichalcogenide (TMDC) monolayers are promising materials for nanoscale light emitters. By coupling TMDCs to optical antennas, the spontaneous emission rate can be greatly enhanced, yielding faster device modulation. However, achieving high rate enhancement is difficult with electrically-injected light emitters compared to optical injection. We demonstrate two device designs to overcome these challenges: 1) a light-emitting capacitor (LEC) coupled to a slot antenna array, and 2) a light-emitting diode (LED) coupled to a nanosquare antenna array. The LEC shows high polarization ratios >30x, while the LED shows >10x enhanced electroluminescence for the antenna coupled device relative to control devices.

Biologic-device combination products using prefilled syringes (PFSs) and autoinjectors (AIs) are popular for biological products administered subcutaneously. Pharmacokinetic (PK) comparability studies commonly provide the scientific data to support introduction of AI presentations via bridging with PFS. A survey of biological products approved by FDA's Center for Drug Evaluation and Research identified 17 biologics license applications (BLAs) with both PFS and AI presentations for subcutaneous (SC) administration, including 16 approved on February 1, 2018, and one with AI presentation under review. A systematic review on the device parameters and the PK comparability studies bridging the two presentations was conducted. Subsequently, whether device parameters or the PK study design may have influenced the PK comparability study results was evaluated. The reported device parameters for AI and PFS are generally consistent across BLAs, whereas the approach to assess PK comparability varied, including the study design. Most PK comparability studies met bioequivalence (BE) criteria. Upon inspection of the studies that did not meet BE criteria, injection depth of AI and the injection site for either AI or PFS were identified as potential influencing factors to the outcome of PK comparability study. This study represents an initial attempt to identify the potential influencing factors on device bridging, including the characteristics of the device and the clinical pharmacology study. These findings may inform the combination product development strategy, specifically design considerations for device and PK comparability studies.

A novel injection locking architecture is demonstrated to simultaneously improve the axial mode linewidth and stabilize the repetition rate of a monolithically integrated mode-locked laser. First, linewidth reduction is demonstrated via multitone injection locking. Then, the passive mode-locked laser is used as a source to make a coupled optoelectronic oscillator, and its RF spectral characteristics are investigated for different optical delays. A novel combination of these two techniques is established by creating a coupled optoelectronic oscillator via multitone injection locking, using an intracavity element as photodetector to generate the feedback signal to a Mach-Zehnder modulator. Using this combination of methods, the axial mode linewidth is reduced by over 6000× to $\sim$ 100 kHz and the RF linewidth is reduced by a factor of 70 at $-$ 30 dBc, resulting in a 3 dB RF linewidth of 400 Hz. The improvement in RF phase noise at 200 kHz offset is $>$ 40 dB. Finally, the system is referenced to a RF synthesizer using a variable voltage phase-shifter and a PID controller. Allan deviation measurements show a resolution limited stability in the repetition rate of $10^{-10}$ at 1 second following a $1/\tau$ trend.

Transition-metal dichalcogenide monolayers have naturally terminated surfaces and can exhibit a near-unity photoluminescence quantum yield in the presence of suitable defect passivation. To date, steady-state monolayer light-emitting devices suffer from Schottky contacts or require complex heterostructures. We demonstrate a transient-mode electroluminescent device based on transition-metal dichalcogenide monolayers (MoS2, WS2, MoSe2, and WSe2) to overcome these problems. Electroluminescence from this dopant-free two-terminal device is obtained by applying an AC voltage between the gate and the semiconductor. Notably, the electroluminescence intensity is weakly dependent on the Schottky barrier height or polarity of the contact. We fabricate a monolayer seven-segment display and achieve the first transparent and bright millimeter-scale light-emitting monolayer semiconductor device., Atomically thin monolayers with high photoluminescence quantum yield are promising for optoelectronic and lighting applications. Here, the authors fabricate a transient-mode electroluminescent device to bypass the requirement of ohmic contacts for electrons and holes, and observe millimetre-scale light emission from a transparent 2D display.

Development and approval of biosimilars is critical for enhancing the availability of affordable, safe, and effective treatment options for patients. Utilization of PD biomarkers can help streamline clinical programs for biosimilar development as the current process can be costly and time consuming. While PD biomarkers have not been prominently used across biosimilar approvals to date, there is ample opportunity to utilize such information alongside or in place of comparative clinical studies with efficacy end point(s) moving forward. PD biomarkers have been successfully utilized as primary end points in PD similarity studies when the PD biomarker was a surrogate end point or a direct measure of clinical outcome. Extending such application beyond surrogate end point PD biomarkers will require some or all the following aspects to be explored: (i) investment in evaluating and synthesizing available information in the literature, (ii) conducting pilot studies, (iii) completing model‐based assessments using available data, and (iv) adopting other novel or emerging technologies, among others. Biosimilar development presents an opportunity for the clinical pharmacology discipline to advance the science around identification and application of PD biomarkers as primary end points in PD similarity studies. The impact on public health is such that the use of PD similarity data in biosimilar programs is a clear means for bringing more affordable, safe, and effective treatments to patients faster.

In laser-foil-printing additive manufacturing, 3D metallic glass structures can be built by laser welding of amorphous foils, layer by layer, upon a crystalline metal substrate. In this paper, weldability studies for laser welding of Zr52.5Ti5Al10Ni14.6Cu17.9 amorphous foils onto a Ti-6Al-4V (Ti 6-4) or Zr 702 substrate are conducted. After laser welding, the weldments are analyzed using X-ray diffractometer, optical microscope, scanning electron microscope equipped with energy dispersive spectroscopy and micro-hardness tester. The results show that Zr 702 is a suitable substrate for Zr-based metallic glass structure since crack-free weld joints can be obtained owing to the formation of ductile α-Zr, while Ti 6-4 is not an appropriate substrate since it has high cracking susceptibility due to the formation of a large amount of hard and brittle intermetallics near the foil-substrate interface. It was found that the mixing between melted substrate and foil is not uniform but exhibits a distinct “swirl” pattern. The swirl structure is more pronounced in Ti 6-4 than in Zr 702 substrate which may contribute to its high cracking susceptibility. The aforementioned mixing leads to partial crystallization of the first amorphous layer; however, fully amorphous is achieved in the additional welding layers.

Summary Various reduced basis element methods are compared for performing transient thermal simulations of integrated circuits. The reduced basis element method is a type of reduced order modeling that takes advantage of repeated geometrical features. It uses a reduced set of basis functions to approximate the solution of a PDE on subdomains (blocks); then these blocks are coupled together to perform a simulation on an entire domain. As the simulations are transient, a proper orthogonal decomposition basis is used, and the proper orthogonal decomposition eigenvalues from each block are used to derive error bounds for the entire simulation. These bounds are used to examine choices of block decompositions for a simplified integrated circuit structure. A decomposition that uses a single block for each transistor device is compared with a decomposition that uses one block for multiple devices. It was found that larger blocks are more computationally efficient; however, the advantage decreases if the devices within a block receive independent signals. Continuous and discontinuous methods of coupling the blocks were also compared. The coupling methods lend themselves to different solution approaches such as static condensation (continuous coupling) and block-based inversion (discontinuous). Static condensation yielded the best convergence rate, accuracy, and operation count. Copyright © 2017 John Wiley & Sons, Ltd.

We report on the flip chip packaging of Micro-Electro-Mechanical System (MEMS)-based digital silicon photonic switching device and the characterization results of 12 × 12 switching ports. The challenges in packaging N 2 electrical and 2N optical interconnections are addressed with single-layer electrical redistribution lines of 25 μm line width and space on aluminum nitride interposer and 13° polished 64-channel lidless fiber array (FA) with a pitch of 127 μm. 50 μm diameter solder spheres are laser-jetted onto the electrical bond pads surrounded by suspended MEMS actuators on the device before fluxless flip-chip bonding. A lidless FA is finally coupled near-vertically onto the device gratings using a 6-degree-of-freedom (6-DOF) alignment system. Fiber-to-grating coupler loss of 4.25 dB/facet, 10-11 bit error rate (BER) through the longest optical path, and 0.4 μs switch reconfiguration time have been demonstrated using 10 Gb/s Ethernet data stream.

An integrated electronic-photonic phase-locked loop (PLL) modulates the frequency of a tunable laser for use in frequency-modulated continuous-wave (FMCW) lidar 3D imaging. The proposed lidar can perform 180k range measurements per second. The rms depth precision is 8 $\mu \text{m}$ at distances of ±5 cm from the range baseline. The range window is 1.4 m, with a precision of 4.2 mm at the edges of the window. Optical circuitry, including input light couplers, waveguides, and photodiodes, is realized on a 3 mm $\times $ 3 mm silicon-photonic chip. The 0.18- $\mu \text{m}$ CMOS ASIC of the same area comprises the front-end transimpedance amplifier, analog electro-optical PLL, and digital control circuitry consuming 1.7 mA from a 1.8 V supply and 14.1 mA from a 5-V supply. The latter includes 12.5-mA bias current for the distributed Bragg reflector section of the tunable laser. The two chips are integrated using through-silicon-vias implemented in the silicon-photonic chip.

A monolithic interferometric tunable laser with a tuning range of 44 nm and linewidth below 700 kHz across all channels is reported. The laser features an intra-cavity coupler consisting of three electro-optically tunable arms with distinct lengths for supermode selection.

Miniaturization of frequency-comb sources could open a host of potential applications in spectroscopy, biomedical monitoring, astronomy, microwave signal generation, and distribution of precise time or frequency across networks. This review article places emphasis on an architecture with a semiconductor mode-locked laser at the heart of the system and subsequent supercontinuum generation and carrier-envelope offset detection and stabilization in nonlinear integrated optics.

Bioactive glasses have recently gained attention in tissue engineering and three-dimensional (3D) bioprinting because of their ability to enhance angiogenesis. Some challenges for developing biological tissues with bioactive glasses include incorporation of glass particles and achieving a 3D architecture mimicking natural tissues. In this study, we investigate the fabrication of scaffolds with a polymer/bioactive glass composite using near-field electrospinning (NFES). An overall controlled 3D scaffold with pores, containing random fibers, is created and aimed to provide superior cell proliferation. Highly angiogenic borate bioactive glass (13-93B3) in 20 wt.% is added to polycaprolactone (PCL) to fabricate scaffolds using the NFES technique. Scaffolds measuring 5 mm × 5 mm × 0.2 mm3 in overall dimensions were seeded with human adipose-derived mesenchymal stem cells to investigate the cell viability. The cell viability on PCL and PCL+glass scaffolds fabricated using NFES technique and 3D printing is compared and discussed. The results indicated higher cell proliferation on 3D biomimetic scaffolds fabricated by NFES technique

Consumers' thirst for data has led to the development of various silicon photonic switching devices that are highly scalable while maintaining their relatively compact form factor at the same time. This demands a paradigm shift in the way these devices are being packaged, as optical and electrical ports are involved. In this article, we proposed a pluggable silicon photonic MEMS switch package with passive optical coupling assembly. This approach shifts fibre coupling away from the package, keeping it “purely electrical.” The pluggable concept is separately demonstrated through spring contacted hybrid assembly and pairs of vertically stack surface gratings. Insertion losses are comparable to planar fibre-to-grating coupling, with relatively broadband transmission and assembly tolerance.

A methodology for fast and accurate thermal simulation of integrated circuits (ICs) is presented based on a multiblock reduced order modeling approach. The model projects the heat equation from a physical domain onto a functional space to represent the thermal solution using a small number of degrees of freedom (DOFs). The approach requires no assumptions about the physical geometry, dimensions, boundary conditions or heat flow pathways, as is usually needed for compact or lumped thermal models. The developed multiblock thermal model is applied to FinFET device/circuit structures including a three-block circuit structure consisting of several NAND gates. The model is verified on multiblock structures against a detailed numerical simulation (DNS). It is shown that the developed multiblock model gives accurate thermal solutions for a multiblock IC structure subjected to power pulse excitations whose pulse frequency, width, shape, and shift in time substantially deviate from those used in model construction. In general, the approach offers accurate thermal solutions as detailed as a DNS with a reduction in the numerical DOF by 5 to 6 orders of magnitude.

Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA's clinical pharmacology review of 121 approved biological products for evaluating and reporting of immunogenicity data. Of the 121 products, 89% (n = 108) reported the incidence of immunogenicity and 49% (n = 59) reported immunogenicity impact on efficacy. However, only 26% (n = 31) reported whether the immunogenicity affected pharmacokinetics. A subset of 16 products reported effects of anti-drug antibodies (ADA) on both systemic clearance and efficacy; 8 of 16 products had increased systemic clearance coinciding with reduced efficacy, and 6 of 16 products had no changes in either clearance or efficacy. Factors contributing to infrequent reporting of the ADA effect on exposure and methods for determining the effect of ADA on exposure are summarized. Measuring ADA and drug concentrations concurrently over time enables the evaluation of ADA impact on pharmacokinetics. Within-subject comparison of concentration data (before vs. after ADA formation) is a useful alternative to between-subject (ADA+ vs. ADA-) comparison when sample size is limited or when the majority of subjects developed ADA. The biological complexity of immune responses presents challenges to quantifying the ADA impact on pharmacokinetics using model-based methods. Our findings support that pharmacokinetic exposure is more sensitive than efficacy endpoints for evaluating ADA effects. A decrease in drug concentration due to formation of ADA during treatment can serve as an early indicator for potential reduced efficacy occurring at a later time.

We report the time-resolved light emission measurement of a nanoscale electrically-injected III-V light emitting diode coupled to a metal antenna. Spontaneous emission lifetime decreases from 1.6 ns to 250 ps with an antenna.

We present a design for an on-chip MEMS-actuated Variable Optical Attenuator (VOA) based on Silicon Photonic MEMS technology. The VOA consists of 30 individual mechanically movable MEMS cantilevers, suspended over an integrated, 1 mu m wide bus waveguide, each terminating with two optical attenuation bars. By exploiting the pull-in instability, electrostatic actuation allows to move the individual cantilevers into proximity of the waveguide, leading to scattering of the evanescent field and thus attenuation of the remaining optical power in the waveguide. Electrodes are placed below the cantilevers for electrostatic actuation. Mechanical stoppers are used to avoid contact between the cantilevers and the electrodes and to keep the bars at a precisely defined distance of 60 nm away from the bus waveguide. The attenuator provides nearly zero insertion loss in OFF state, while in ON state, the attenuation range is defined by the number of actuated digital attenuation cantilevers and can be adjusted in discrete increments of only 1.2 dB. Owing to the small size, fast microsecond scale response time can be achieved, and electrostatic MEMS actuation allows for broadband and low-power operation. Our design exhibits a compact footprint of 30 mu m x 45 mu m, attenuation from 0 dB to 36 dB, while keeping return loss below 27 dB. To the best of our knowledge, this is the first presentation of a design of a VOA in Silicon Photonic MEMS technology.

We report on a novel two-dimensional (2-D) optical phased arrays with 25,600 addressable phase shifters made of diffraction gratings with in-plane movement. The phase shift is independent of wavelength, and only depends on the displacement of the grating. The large optical aperture 3.2×3.1mm2 produces a narrow beam (0.028°×0.029°) steerable over a field-of-view of 4.4°×4.6° at 1550nm wavelength, with a maximum response time of 4.2μs.

We demonstrate bright electroluminescence in WSe 2 monolayers using pulsed injection, without the use of split gates, chemical doping, or heterostructures. Electroluminescence quantum efficiency approaches that of photoluminescence, indicating efficient exciton formation with injected carriers.

The rate of spontaneous emission can be enhanced using either a metallic antenna or a dielectric cavity. Here we adapt elements of both types for a novel metallo-dielectric structure that exhibits ultra-low mode volume, V eff = 4.53×10−6λ3.

Repetition rate stabilization of an injection locked chip-scale mode-locked laser and progress towards carrier envelope offset frequency stabilization using chalcogenide waveguides for supercontinuum generation and a bulk PPLN for second harmonic generation are presented.

We design and fabricate the packaging of 128 × 128 silicon photonic MEMS switch device using through glass via (TGV) interposer and pitch reducing fibre array. The switch device contains 16384 MEMS switch cells and 272 grating couplers spaced at 63.5 μm in a compact footprint of 17.4 mm × 16 mm. The apodised grating couplers designed for 1300 nm have an insertion loss of 2.5 dB/facet at 10° coupling angle. The 0.5 mm thick glass interposer contains 512 electrical vias while the pitch reducing optical coupling array is polished to 40° for planar coupling.

Purpose – The purpose of this paper is to utilize the selective laser sintering (SLS) process to fabricate scaffolds with complex pore shapes and investigate the effects of pore geometry in vitro. The pore geometry of scaffolds intended for use in bone repair is one of the most important parameters used to determine the rate of bone regeneration. Design/methodology/approach – Scaffolds with five different architectures, having approximately 50 per cent porosity, were fabricated with silicate (13–93) and borate (13–93B3)-based bioactive glasses using the SLS process. An established late-osteoblasts/early-osteocytes cell line was used to perform cell proliferation tests on the scaffolds. The cell-seeded scaffolds were incubated for two, four and six days followed by MTT assay to quantify the metabolically active cells. Findings – The results indicated that the cells proliferate significantly more on the scaffolds which mimic the trabecular bone architecture compared to traditional lattice structures. The surface roughness of the SLS-fabricated scaffolds drives the initial cell proliferation which is followed by curvature-driven cell proliferation. Originality/value – There have been very few studies on the effects of pore geometry on tissue growth and the existing reports do not provide clear indications. Instead of using bio-polymer or titanium-based scaffolds, we use bioactive glass scaffolds. The results obtained from this study add to the understanding of the effect of pore geometry on cell proliferation, which is based on the experimental data and analysis of the scaffolds’ surface curvature.

An accurate thermal circuit model for 2-D silicon-on-insulator (SOI) MOSFETs is presented to account for nonisothermal effects. The circuit model is modified from an approach developed earlier for the temperature distribution in 2-D SOI MOSFETs. A generalized approach to establishing a nonisothermal circuit and its circuit elements is presented for different SOI structures, such as multidevices on a single island and multifinger structure. The developed circuit model is verified with the finite-element method (FEM) in different SOI structures, including a structure coupled with interconnects. Heat flow to the contacts, poly gate, and buried oxide (BOX)/field oxide (FOX) is examined. Heat exchange via FOX between neighboring islands is carefully investigated, as compared to the FEM. It is shown from the developed model and FEM simulations that heat exchange via FOX between two thin islands is negligible if the distance between the islands is near or greater than the island thickness plus the BOX thickness.

Large 200-fold increase in the spontaneous emission rate is experimentally observed in an electrically-injected nanoscale LED coupled to a cavity-backed slot antenna; an important achievement toward a LED that is faster than the laser.

We report the stabilization of a 10 GHz monolithic passively mode-locked laser using a novel combination of multitone injection locking and regenerative mode-locking via optoelectronic loop. Comb-teeth linewidths are narrowed by 4000x and repetition rate is stabilized to better than 10−10/τ at 1 second.

We demonstrate low surface recombination velocity (∼8700 cm/s) and reduction of non-radiative lifetime in an InP/InGaAs nanoscale light emitting diode using a sacrificial Al2O3 layer. We predict high efficiency operation after modest enhancement of spontaneous emission rate with an optical antenna.

We review the state of the art of silicon photonic switches with MEMS actuation, which have high scalability, low power consumption, and digital switching characteristic. We also present the potential of polarization insensitive switching by MEMS-actuated silicon photonic switches.

With optical antennas, spontaneous light emission becomes faster than stimulated emission, but the enhancement is limited by optical losses through the “anomalous skin effect”. Maintaining 50% efficiency, a 10x speedup beyond stimulated emission should be possible. The antenna-LED will replace the laser for on-chip optical communication.

Using the Vernier effect and the interference between its three branches, the proposed self-imaging multi-mode-interferometer (MMI)-based tunable laser can access all ITU channels across C-band with high side-mode suppression ratios (SMSR).

Silicon nitride spot-size converters were fabricated in a damascene process to improve the performance of supercontinuum generation in arsenic-free chalcogenide waveguides. Supercontinuum generation covering 950–1750 nm with 200 pJ pulses is demonstrated.

A novel method of regenerative mode-locking using multi-tone optical injection locking of a chip-scale CPM laser is demonstrated. This technique achieves simultaneous reduction in RF phase noise (8x) and narrows the longitudinal mode by 4,000x.

We present a novel racetrack colliding-pulse mode-locked laser with external pulse-picking and optical amplification monolithically integrated on InP. Optical pulses with FWHM of 2.36 ps are observed under hybrid mode-locking at 10 GHz repetition rate.

Optical phased array (OPA) is a key enabling element for solid state LIDAR (light detection and ranging). In this paper, we demonstrate a novel MEMS micromirror array OPA. Vertical combdrive actuators are integrated underneath the mirrors to achieve a small pitch (2.4μm) and a large field of view (22° at 905nm wavelength and 40° at 1550nm). The OPA has 2μs response time, and 10V actuation voltage.

Three-dimensional (3D) bioprinting technologies have shown great potential in the fabrication of 3D models for different human tissues. Stem cells are an attractive cell source in tissue engineering as they can be directed by material and environmental cues to differentiate into multiple cell types for tissue repair and regeneration. In this study, we investigate the viability of human adipose-derived mesenchymal stem cells (ASCs) in alginate-gelatin (Alg-Gel) hydrogel bioprinted with or without bioactive glass. Highly angiogenic borate bioactive glass (13-93B3) in 50 wt% is added to polycaprolactone (PCL) to fabricate scaffolds using a solvent-based extrusion 3D bioprinting technique. The fabricated scaffolds with 12 × 12 × 1 mm3 in overall dimensions are physically characterized, and the glass dissolution from PCL/glass composite over a period of 28 days is studied. Alg-Gel composite hydrogel is used as a bioink to suspend ASCs, and scaffolds are then bioprinted in different configurations: Bioink only, PCL+bioink, and PCL/glass+bioink, to investigate ASC viability. The results indicate the feasibility of the solvent-based bioprinting process to fabricate 3D cellularized scaffolds with more than 80% viability on day 0. The decrease in viability after 7 days due to glass concentration and static culture conditions is discussed. The feasibility of modifying Alg-Gel with 13-93B3 glass for bioprinting is also investigated, and the results are discussed.

Transition metal dichalcogenide (TMDC) monolayers are promising materials for next-generation nanoscale optoelectronics, including high-speed light sources and detectors. However, most past reports on TMDC light-emitting diodes are limited to operation in high vacuum, while most applications require operation under ambient conditions. In this work, we study the time-resolved electroluminescence of monolayer WSe2 p-n junctions under ambient conditions and identify the decay in current over time as the main issue preventing stable device operation. We show that pulsed voltage bias overcomes this issue and results in bright electroluminescence under ambient conditions. This is achieved in a simple single-gate structure, without the use of dual gates, heterostructures, or doping methods. Internal quantum efficiency of electroluminescence reaches ∼1%, close to the photoluminescence quantum efficiency, indicating efficient exciton formation with injected carriers. Emission intensity is stable over hours of device operation. Finally, our device exhibits ∼15 ns rise and fall times, the fastest direct modulation speed reported for TMDC light-emitting diodes.Transition metal dichalcogenide (TMDC) monolayers are promising materials for next-generation nanoscale optoelectronics, including high-speed light sources and detectors. However, most past reports on TMDC light-emitting diodes are limited to operation in high vacuum, while most applications require operation under ambient conditions. In this work, we study the time-resolved electroluminescence of monolayer WSe2 p-n junctions under ambient conditions and identify the decay in current over time as the main issue preventing stable device operation. We show that pulsed voltage bias overcomes this issue and results in bright electroluminescence under ambient conditions. This is achieved in a simple single-gate structure, without the use of dual gates, heterostructures, or doping methods. Internal quantum efficiency of electroluminescence reaches ∼1%, close to the photoluminescence quantum efficiency, indicating efficient exciton formation with injected carriers. Emission intensity is stable over hours of devi...

We present a design for an analog phase shifter based on Silicon Photonic MEMS technology. The operation principle is based on a two-step parallel plate electrostatic actuation mechanism to bring a vertically movable suspended tapered waveguide in a first step into proximity of the bus waveguide and to tune the phase of the propagating coupled mode in a second step by actuation of the suspended waveguide to tune the vertical gap. In the coupled state, the effective index of the optical supermode and the total accumulated phase delay can be varied by changing the vertical separation between the adiabatically tapered suspended and the fixed bus waveguides. Simulations predict that pi phase shift can be achieved with an actuation voltage of 19 V, corresponding to a displacement of 19 nm. With an adiabatic coupler geometry, the optical signal can be coupled between the moving waveguide and the bus waveguide with low loss in a wide wavelength range from 1.5 mu m to 1.6 mu m keeping the average insertion loss below 0.3 dB. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

6516 Background: Non-adherence to AI’s for breast cancer is common and increases risk of recurrence. Text messaging (TM) has been shown to increase adherence to medications for chronic conditions. We conducted a multicenter randomized trial to evaluate if TM reminders improve AI adherence. Methods: Patients taking an AI for ≥30 days and having ≥36 mos of planned therapy were eligible. Patients were randomly assigned 1:1 to receive either TM or NO-TM twice a week for 36 mos. Randomization was stratified by length of time on prior AI therapy ( < 12 (64%) vs. 12-24 mos (36%)) and AI class (anastrozole, letrozole, exemestane). Content themes of the 36 TMs focused on overcoming barriers to adherence. Patients were assessed for discontinuation of AIs every 3 mos for 36 mos. The primary outcome was time to non-adherence, where non-adherence was defined as urine AI metabolite assay results satisfying the following: < 10 [units], undetectable, or no submitted specimen. A stratified Log-rank test was conducted. Multiple sensitivity analyses were performed using Cox regression. Results: In total, 724 patients were registered between May, 2012 and September, 2013, among whom 696 (338/360 (93.9%) on TM and 338/364 (92.9%) on NO-TM) were eligible and adherent at baseline. Observed (time-independent) adherence at 36 mos was 55.4% for TM and 55.4% for NO-TM. The primary analysis showed no difference in time-to-adherence failure between patients on the TM and NO-TM arms (HR = 0.89, 95% CI:0.76,1.05 p = .18). An analysis of negative urine tests alone resulted in similar non-significant results. With missed appointments not counted as failures, time to self-reported discontinuation (89.6% vs. 89.7%; HR = 1.17, 95% CI:0.69-1.98, p = .57) and site reported discontinuation (78.1% vs. 81.1%; HR = 1.31, 95% CI:0.86-2.01, p = .21) were also similar between the 2 groups. Conclusions: As the first large long-term randomized trial of an intervention directed at improving AI adherence, we found high rates of AI discontinuation. Bi-weekly text reminders did not improve adherence to AIs compared to usual care. Improving long—term adherence will likely require sustained behavioral interventions and support. Clinical trial information: NCT01515800.

Fast optical switches have been proposed as a promising alternative to enable continual scaling of data centers with increasing size and data rates. Silicon photonics is a compelling platform for large-scale integrated photonic switches, leveraging advanced manufacturing foundries for electronic integrated circuits. In the past decade, the port counts of silicon photonic switches have increased steadily to 128×128. Further scaling of the switch is constrained by the maximum reticle size (2–3 cm) of lithography tools. Here, we propose to use wafer-scale integration to overcome the die size limit. As a proof of concept demonstration, we fabricated a 240×240 switch by lithographically stitching a 3×3 array of identical 80×80 switch blocks across reticle boundaries. Stitching loss is substantially reduced (0.004 dB) by tapering the waveguide width to 10 μm. The fabricated switch on a 4 cm×4 cm chip exhibits a maximum on-chip loss of 9.8 dB, an ON/OFF ratio of 70 dB, and switching times of less than 400 ns. To our knowledge, this is the largest integrated photonic switch ever reported. The loss-to-port count ratio (0.04 dB/port) is also the lowest.

We report on a laser frequency sweep linearization method by iterative learning pre-distortion for frequency-modulated continuous-wave (FMCW) light detection and ranging (LiDAR) systems. A pre-distorted laser drive voltage waveform that results in a linear frequency sweep is obtained by an iterative learning controller, and then applied to the FMCW LiDAR system. We have also derived a fundamental figure of merit for the maximum residual nonlinearity needed to achieve the transform-limited range resolution. This method is experimentally tested using a commercial vertical cavity surface-emitting laser (VCSEL) and a distributed feedback (DFB) laser, achieving less than 0.005% relative residual nonlinearity of frequency sweep. With the proposed method, high-performance FMCW LiDAR systems can be realized without expensive linear lasers, complex linearization setups, or heavy post-processing.

We report on the packaging of the 50 × 50 MEMS-actuated silicon photonics switching device through flip-chip assembly and a lidless 64-channel fibre array polished at 13° angle. The device, measuring 10 mm × 10 mm, contains more than 2500 bond pads with a dimension of 65 μm × 65 μm, with the actuating MEMS structures locating 15 μm away at 4 sides of each bond pads. An average switching voltage of 35 V recorded at package level complies with data recorded during device probing while fibre-to-grating coupler loss was measured to be 4.25dB / facet at around 1550nm.

We report on wafer-scale processing of GeSbS-based chalcogenide waveguides on silicon substrates. High Q-factor (106), low propagation loss (0.2 dB/cm), and supercontinuum generation in a 2-cm-long waveguide with 120 pJ pulses are demonstrated.