Comparison of Monolithic Optical Frequency Comb Generators Based on Passively Mode-Locked Lasers for Continuous Wave mm-Wave and Sub-THz Generation

In this paper, two different Passive Mode-Locked Laser Diodes (PMLLD) structures, a Fabry-Perot cavity and a ring cavity laser are characterized and evaluated as monolithic Optical Frequency Comb Generators (OFCG) for CW sub-THz generation. An extensive characterization of the devices under study is carried out based on an automated measurement system that systematically evaluates the dynamic characteristics of the devices, focusing on the figures of merit that define the optimum performance of a pulsed laser source when considered as an OFCG. Sub-THz signals generated with both devices at 60 GHz and 90 GHz are presented and analyzed in terms of electrical linewidth to compare such components for mm-Wave and sub-THz photonic generation. This work offers a systematic comparison of PMLLD devices for OFCG operation and provides reference information of the performance of two different device topologies that can be used for the implementation of photonic integrated sub-THz CW generation.We acknowledge COBRA Research Institute, Eindhoven University of Technology, the Netherlands for the fabrication of the ring lasers within the joint European platform for InP-based components and circuits, JePPIX.Publicad

Effective electro-optical modulation with high extinction ratio by a graphene-silicon microring resonator

Graphene opens up for novel optoelectronic applications thanks to its high carrier mobility, ultra-large absorption bandwidth, and extremely fast material response. In particular, the opportunity to control optoelectronic properties through tuning of Fermi level enables electro-optical modulation, optical-optical switching, and other optoelectronics applications. However, achieving a high modulation depth remains a challenge because of the modest graphene-light interaction in the graphene-silicon devices, typically, utilizing only a monolayer or few layers of graphene. Here, we comprehensively study the interaction between graphene and a microring resonator, and its influence on the optical modulation depth. We demonstrate graphene-silicon microring devices showing a high modulation depth of 12.5 dB with a relatively low bias voltage of 8.8 V. On-off electro-optical switching with an extinction ratio of 3.8 dB is successfully demonstrated by applying a square-waveform with a 4 V peak-to-peak voltage.Comment: 12 pages, including 7 figure

Demonstration of a self-pulsing photonic crystal Fano laser

Semiconductor lasers in use today rely on mirrors based on the reflection at a cleaved facet or Bragg reflection from a periodic stack of layers. Here, we demonstrate an ultra-small laser with a mirror based on the Fano resonance between a continuum of waveguide modes and the discrete resonance of a nanocavity. The Fano resonance leads to unique laser characteristics. Since the Fano mirror is very narrow-band compared to conventional lasers, the laser is single-mode and in particular, it can be modulated via the mirror. We show, experimentally and theoretically, that nonlinearities in the mirror may even promote the generation of a self-sustained train of pulses at gigahertz frequencies, an effect that was previously only observed in macroscopic lasers. Such a source is of interest for a number of applications within integrated photonics

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases

IL-21 induces in vivo immune activation of NK cells and CD8+ T cells in patients with metastatic melanoma and renal cell carcinoma

PURPOSE: Human interleukin-21 (IL-21) is a class I cytokine previously reported in clinical studies on immune responsive cancers. Here we report the effects of systemic IL-21 therapy on the immune system in two phase 1 trials with this novel cytokine. EXPERIMENTAL DESIGN: Recombinant IL-21 was administered by intravenous bolus injection at dose levels from 1 to 100 microg/kg using two planned treatment regimens: thrice weekly for 6 weeks (3/week); or once daily for five consecutive days followed by nine dose-free days (5 + 9). The following biomarkers were studied in peripheral blood mononuclear cells (PBMC) during treatment: phosphorylation of STAT3, alterations in the composition of leukocyte subsets, ex vivo cytotoxicity, expression of effector molecules in enriched CD8(+) T cells and CD56(+) NK cells by quantitative RT-PCR, and gene array profiling of CD8(+) T cells. RESULTS: Effects of IL-21 were observed at all dose levels. In the 5 + 9 regimen IL-21 induced a dose dependent decrease in circulating NK cells and T cells followed by a return to baseline in resting periods. In both CD8(+) T cells and CD56(+) NK cells we found up-regulation of perforin and granzyme B mRNA. In addition, full transcriptome analysis of CD8(+) T cells displayed changes in several transcripts associated with increased cell cycle progression, cellular motility, and immune activation. Finally, cytotoxicity assays showed that IL-21 enhanced the ability of NK cells to kill sensitive targets ex vivo. CONCLUSIONS: IL-21 was biologically active at all dose levels administered with evidence of in vivo NK cell and CD8(+) T cell activation