Impact of waveguide cross section on nonlinear impairments in integrated optical filters for WDM communication systems

Integrated optical chips enabling the realization of low-cost optical network units (ONU) is of great interest both for data centre solutions and for passive optical networks. In particular, in the frame of passive optical networks an interesting possibility is constituted by the presence, in the ONU of a Wavelength Division Multiplexing (WDM) filter [1] One of the most popular solution is based on a micro-ring resonators. The filter doesn’t introduce any relevant impairment in the downstream signal, as the optical power reaching the ONU, at the resonant wavelength, is generally so small that nonlinear effects can be generally neglected. Nevertheless, if the upstream signal, that generally has a much higher power, has to pass through the same resonator can undergo nonlinear effects like two-photon absorption (TPA), free-carriers absorption (FCA), and free-carrier dispersion (FCD) [2]. In this abstract we show the results of an experimental analysis we carried out in order to investigate the impact of optical nonlinear effects in WDM integrated micro-filters exploiting different designs (double- and triple- resonators structures, racetracks, rings, curved coupling regions, etc.) and exhibiting significantly different waveguide cross-sections (from 500 × 220 nm to 825 × 100 nm). The nonlinear behaviour evaluation has been carried out by performing two different sets of experiments. In the first one the amplified spontaneous emission emitted by an Er-doped fiber amplifier was filtered (by using a tunable filter with 5 nm band-width) and then amplified and then input by grating-assisted coupling to the filtering structures. Changes of filter transfer function were observed as a function of the input power. Conversely, in the second setup a narrowband CW-laser was used, and the behaviour of output power as a function of the input power was recorded

Regulation of CD4+NKG2D+ Th1 cells in patients with metastatic melanoma treated with sorafenib : role of IL-15Rα and NKG2D triggering

Beyond cancer-cell intrinsic factors, the immune status of the host has a prognostic impact on patients with cancer and influences the effects of conventional chemotherapies. Metastatic melanoma is intrinsically immunogenic, thereby facilitating the search for immune biomarkers of clinical responses to cytotoxic agents. Here, we show that a multi-tyrosine kinase inhibitor, sorafenib, upregulates interleukin (IL)-15Rα in vitro and in vivo in patients with melanoma, and in conjunction with natural killer (NK) group 2D (NKG2D) ligands, contributes to the Th1 polarization and accumulation of peripheral CD4+NKG2D+ T cells. Hence, the increase of blood CD4+NKG2D+ T cells after two cycles of sorafenib (combined with temozolomide) was associated with prolonged survival in a prospective phase I/II trial enrolling 63 patients with metastatic melanoma who did not receive vemurafenib nor immune checkpoint-blocking antibodies. In contrast, in metastatic melanoma patients treated with classical treatment modalities, this CD4+NKG2D+ subset failed to correlate with prognosis. These findings indicate that sorafenib may be used as an "adjuvant" molecule capable of inducing or restoring IL-15Rα/IL-15 in tumors expressing MHCclass I-related chain A/B (MICA/B) and on circulating monocytes of responding patients, hereby contributing to the bioactivity of NKG2D+ Th1 cells.peer-reviewe

Transmitter made up of a Silicon Photonic IC and its Flip-Chipped CMOS IC DriverTargeting implementation in FDMA-PON

We report on the design, fabrication and characterization of a reflective transmitter targeting implementation in Passive Optical Networks (PON) with Frequency Division Multiplexed Access (FDMA). It is made up of a Silicon Photonic Integrated Circuit (Si-PIC) comprising a Reflective Mach Zehnder Modulator (R-MZM) and its flip chipped CMOS Electronic Integrated Circuit (EIC) driver, the two ICs being interconnected by means of high density and low parasitic copper micro pillars. Several transmissions, in an FDMA PON context, are successfully demonstrated using 500MBaud QPSK and 16-QAM modulated subcarriers, achieving Bit Error Rate (BER) below 2.10-3. For QPSK-modulated subcarriers (respectively 16-QAM), the available access frequency bandwidth is measured to be [1-7GHz] (respectively [2-4GHz]) with an available loss budget of 9dB (respectively 5dB). Improvements of the Si-PIC are further identified to achieve compliancy with 31dB ODN loss

Hybrid III-V on silicon lasers for photonic integrated circuits on silicon

This paper summarizes recent advances of integrated hybrid InP/SOI lasers and transmitters based on wafer bonding. At first the integration process of III-V materials on silicon is described. Then the paper reports on the results of single wavelength distributed Bragg reflector lasers with Bragg gratings etched on silicon waveguides. We then demonstrate that, thanks to the high-quality silicon bend waveguides, hybrid III-V/Si lasers with two integrated intra-cavity ring resonators can achieve a wide thermal tuning range, exceeding the C band, with a side mode suppression ratio higher than 40 dB. Moreover, a compact array waveguide grating on silicon is integrated with a hybrid III-V/Si gain section, creating a wavelength-selectable laser source with 5 wavelength channels spaced by 400 GHz. We further demonstrate an integrated transmitter with combined silicon modulators and tunable hybrid III-V/Si lasers. The integrated transmitter exhibits 9 nm wavelength tunability by heating an intra-cavity ring resonator, high extinction ratio from 6 to 10 dB, and excellent bit-error-rate performance at 10 Gb/s

Shifting the Balance of Activating and Inhibitory Natural Killer Receptor Ligands on BRAF V600E Melanoma Lines with Vemurafenib

International audienceOver 60% of human melanoma tumors bear a mutation in the BRAF gene. The most frequent mutation is a substitution at codon 600 (V600E), leading to a constitutively active BRAF and over-activation of the MAPK pathway. Patients harboring mutated BRAF respond to kinase inhibitors such as vemurafenib. However, these responses are transient, and relapses are frequent. Melanoma cells are efficiently lysed by activated natural killer (NK) cells. Melanoma cells express several stress-induced ligands that are recognized by activating NK-cell receptors. We have investigated the effect of vemurafenib on the immunogenicity of seven BRAF-mutated melanoma cells to NK cells and on their growth and sensitivity to NK-cell–mediated lysis. We showed that vemurafe-nib treatment modulated expression of ligands for two activating NK receptors, increasing expression of B7-H6, a ligand for NKp30, and decreasing expression of MICA and ULBP2, ligands for NKG2D. Vemurafenib also increased expression of HLA class I and HLA-E molecules, likely leading to higher engagement of inhibitory receptors (KIRs and NKG2A, respectively), and decreased lysis of vemurafenib-treated melanoma cell lines by cytokine-activated NK cells. Finally, we showed that whereas batimastat (a broad-spectrum matrix metalloprotease inhibitor) increased cell surface ULBP2 by reducing its shedding, vemurafe-nib lowered soluble ULBP2, indicating that BRAF signal inhibition diminished expression of both cell-surface and soluble forms of NKG2D ligands. Vemurafenib, inhibiting BRAF signaling, shifted the balance of activatory and inhibitory NK ligands on melanoma cells and displayed immunoregulatory effects on NK-cell functional activities

Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer

43siAside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk. Baseline stool Akk was associated with increased objective response rates and overall survival in multivariate analyses, independent of PD-L1 expression, antibiotics, and performance status. Intestinal Akk was accompanied by a richer commensalism, including Eubacterium hallii and Bifidobacterium adolescentis, and a more inflamed tumor microenvironment in a subset of patients. However, antibiotic use (20% of cases) coincided with a relative dominance of Akk above 4.8% accompanied with the genus Clostridium, both associated with resistance to ICI. Our study shows significant differences in relative abundance of Akk that may represent potential biomarkers to refine patient stratification in future studies.reservedopenDerosa, Lisa; Routy, Bertrand; Thomas, Andrew Maltez; Iebba, Valerio; Zalcman, Gerard; Friard, Sylvie; Mazieres, Julien; Audigier-Valette, Clarisse; Moro-Sibilot, Denis; Goldwasser, François; Silva, Carolina Alves Costa; Terrisse, Safae; Bonvalet, Melodie; Scherpereel, Arnaud; Pegliasco, Hervé; Richard, Corentin; Ghiringhelli, François; Elkrief, Arielle; Desilets, Antoine; Blanc-Durand, Felix; Cumbo, Fabio; Blanco, Aitor; Boidot, Romain; Chevrier, Sandy; Daillère, Romain; Kroemer, Guido; Alla, Laurie; Pons, Nicolas; Le Chatelier, Emmanuelle; Galleron, Nathalie; Roume, Hugo; Dubuisson, Agathe; Bouchard, Nicole; Messaoudene, Meriem; Drubay, Damien; Deutsch, Eric; Barlesi, Fabrice; Planchard, David; Segata, Nicola; Martinez, Stéphanie; Zitvogel, Laurence; Soria, Jean-Charles; Besse, BenjaminDerosa, Lisa; Routy, Bertrand; Thomas, Andrew Maltez; Iebba, Valerio; Zalcman, Gerard; Friard, Sylvie; Mazieres, Julien; Audigier-Valette, Clarisse; Moro-Sibilot, Denis; Goldwasser, François; Silva, Carolina Alves Costa; Terrisse, Safae; Bonvalet, Melodie; Scherpereel, Arnaud; Pegliasco, Hervé; Richard, Corentin; Ghiringhelli, François; Elkrief, Arielle; Desilets, Antoine; Blanc-Durand, Felix; Cumbo, Fabio; Blanco, Aitor; Boidot, Romain; Chevrier, Sandy; Daillère, Romain; Kroemer, Guido; Alla, Laurie; Pons, Nicolas; Le Chatelier, Emmanuelle; Galleron, Nathalie; Roume, Hugo; Dubuisson, Agathe; Bouchard, Nicole; Messaoudene, Meriem; Drubay, Damien; Deutsch, Eric; Barlesi, Fabrice; Planchard, David; Segata, Nicola; Martinez, Stéphanie; Zitvogel, Laurence; Soria, Jean-Charles; Besse, Benjami

TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer

Natural Killer (NK) cells control metastatic dissemination of murine tumors and are an important prognostic factor in several human malignancies. However, tumor cells hijack many of the NK cell functional features compromising their tumoricidal activity. Here, we show a deleterious role of the TNFα/TNFR2/BIRC3/TRAF1 signaling cascade in NK cells from the tumor microenvironment (TME). TNFα induces BIRC3/cIAP2 transcripts and reduces NKp46/NCR1 transcription and surface expression on NK cells, promoting metastases dissemination in mice and poor prognosis in GIST patients. NKp30 engagement, by promoting the release of TNFα, also contributes to BIRC3 upregulation, and more so in patients expressing predominantly NKp30C isoforms. These findings reveal that in the absence of IL-12 or a Th1-geared TME, TNFα can be considered as a negative regulatory cytokine for innate effectors

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed