We present a comprehensive design, fabrication, and characterization analysis of compact silicon-on-insulator bandpass filters with widely tunable bandwidth. The filter architecture is based on an ...unbalanced Mach-Zehnder interferometer loaded with a pair of ring resonators. A wide bandwidth tunability (from 10% to 90% FSR) can be achieved by controlling the resonant frequency of the rings while preserving a good filter off-band rejection. Design rules are provided that take into account fabrication tolerances as well as losses. Furthermore, the use of tunable couplers allows a more flexible shaping of the spectral response of the filter. The sensitivity with respect to nonlinear effects is carefully investigated. Operation over a wavelength spectrum of 20 nm is demonstrated, making the device suitable for channel subset selection in WDM systems, reconfigurable filters for gridless networking and adaptive filtering of signals.
Automatic reconfiguration and feedback controlled routing is demonstrated in an 8 × 8 silicon photonic switch fabric based on Mach-Zehnder interferometers. The use of noninvasive contactless ...integrated photonic probes (CLIPPs) enables real-time monitoring of the state of each switching element individually. Local monitoring provides direct information on the routing path, allowing an easy sequential tuning and feedback controlled stabilization of the individual switching elements, thus making the switch fabric robust against thermal crosstalk, even in the absence of a cooling system for the silicon chip. Up to 24 CLIPPs are interrogated by a multichannel integrated ASIC wire bonded to the photonic chip. Optical routing is demonstrated on simultaneous WDM input signals that are labeled directly on-chip by suitable pilot tones without affecting the quality of the signals. Neither preliminary circuit calibration nor lookup tables are required, being the proposed control scheme inherently insensible to channels power fluctuations.
Abstract
Aims
Cardiac amyloidosis typically manifests as heart failure with preserved left ventricular function due to extracellular plaques comprising aggregated TTR. Despite recent success in ...halting disease progression with a TTR stabilizer and encouraging preliminary findings with TTR silencers, these agents are not targeting preexisting plaques. Herein, we report the development of a novel monoclonal antibody capable of attenuating experimental cardiac amyloidosis.
Methods and results
We generated an IgG1 monoclonal antibody against aggregated TTR that immunoprecipitated the protein in the sera of patients with wild-type ATTR (wtATTR) and robustly stained cardiac plaques from patients. The antibody was shown to facilitate aggregated-TTR uptake by various myeloid cells and to protect cardiomyocytes from TTR-inducible toxicity. In a novel in vivo model of wtATTR amyloidosis, the antibody enhanced the disappearance of the pyrophosphate signals attesting for a rapid amyloid deposit removal and degradation and also exhibited improved echocardiographic measures of cardiac performance. Importantly, a capture ELISA developed based on the antibody exhibited higher levels of aggregated TTR in the sera of wtATTR amyloidosis patients as compared to control patients with heart failure suggesting a potential applicability in diagnosis and pharmacodynamic guidance of dosing.
Conclusion
We developed a proprietary antibody targeting aggregated TTR that exhibits beneficial effects in a novel experimental wtATTR model and also possesses a potential diagnostic utility. The antibody could potentially be tested as a disease modifying agent in ATTR amyloidosis.
The highly sensitive nature of slot waveguide micro-resonator power couplers is discussed with respect to the resonator geometry and evanescent coupler design. A modified, tri-bar, evanescent field ...coupler is demonstrated that shows reduced sensitivity to ring radius as compared with conventional couplers, while maintaining a compact beat-length of only a few micrometers. With the measurement of bending losses of curved slot waveguides, critically coupled ring resonators were designed and fabricated, exhibiting a resonance extinction exceeding 22 dB.
Sustained undetectable molecular residual disease (UMRD) is obtained in a minority of patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. It remains unclear whether these ...patients are definitively cured of their leukemia or whether leukemic stem cells (LSCs) persist in their BM. We have evaluated the presence of BCR-ABL–expressing marrow LSCs in 6 patients with chronic myeloid leukemia with sustained UMRD induced by IFN-α (n = 3), imatinib mesylate after IFN-α failure (n = 2), and dasatinib after imatinib intolerance (n = 1). Purified CD34+ cells were used for clonogenic and long-term culture-initiating cell assays performed on classic or HOXB4-expressing MS-5 feeders. Using this strategy, we identified BCR-ABL–expressing LSCs in all patients. Interestingly, long-term culture-initiating cell assays with MS-5/HOXB4 stromal feeders increased detected numbers of LSCs in 3 patients. The relation between LSC persistency and a potential risk of disease relapse for patients with durable UMRD (on or off tyrosine kinase inhibitor therapy) warrants further investigation.
Glioblastoma (GBM) is a devastating cancer with basically no curative treatment. Even with aggressive treatment, the median survival is disappointing 14 months. Surgery remains the key treatment and ...the postoperative survival is determined by the extent of resection. Unfortunately, the invasive growth with irregular infiltrating margins complicates an optimal surgical resection. Precise intraoperative tumor visualization is therefore highly needed and molecular targeted near-infrared (NIR) fluorescence imaging potentially constitutes such a tool. The urokinase-type Plasminogen Activator Receptor (uPAR) is expressed in most solid cancers primarily at the invading front and the adjacent activated peritumoral stroma making it an attractive target for targeted fluorescence imaging. The purpose of this study was to develop and evaluate a new uPAR-targeted optical probe, IRDye800CW-AE344, for fluorescence guided surgery (FGS). Methods: In the present study we characterized the fluorescent probe with regard to binding affinity, optical properties, and plasma stability. Further, in vivo imaging characterization was performed in nude mice with orthotopic human patient derived glioblastoma xenografts, and we performed head-to-head comparison within FGS between our probe and the traditional procedure using 5-ALA. Finally, the blood-brain barrier (BBB) penetration was characterized in a 3D BBB spheroid model. Results: The probe effectively visualized GBM in vivo with a tumor-to-background ratio (TBR) above 4.5 between 1 to 12 h post injection and could be used for FGS of orthotopic human glioblastoma xenografts in mice where it was superior to 5-ALA. The probe showed a favorable safety profile with no evidence of any acute toxicity. Finally, the 3D BBB model showed uptake of the probe into the spheroids indicating that the probe crosses the BBB. Conclusion: IRDye800CW-AE344 is a promising uPAR-targeted optical probe for FGS and a candidate for translation into human use.
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