| 1. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 2. |
- Lévy, Romain, et al.
(författare)
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Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
- 2023
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
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Tidskriftsartikel (refereegranskat)abstract
- Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
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| 3. |
- Abolhassani, Hassan, et al.
(författare)
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Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer Nature. - 0271-9142 .- 1573-2592. ; 42:3, s. 471-483
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Tidskriftsartikel (refereegranskat)abstract
- Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1, underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.
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| 4. |
- Carlborg, Carl Fredrik, et al.
(författare)
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A packaged optical slot-waveguide ring resonator sensor array for multiplex label-free assays in labs-on-chips
- 2010
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 10:3, s. 281-290
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Tidskriftsartikel (refereegranskat)abstract
- We present the design, fabrication, and characterisation of an array of optical slot-waveguide ring resonator sensors, integrated with microfluidic sample handling in a compact cartridge, for multiplexed real-time label-free biosensing. Multiplexing not only enables high throughput, but also provides reference channels for drift compensation and control experiments. Our use of alignment tolerant surface gratings to couple light into the optical chip enables quick replacement of cartridges in the read-out instrument. Furthermore, our novel use of a dual surface-energy adhesive film to bond a hard plastic shell directly to the PDMS microfluidic network allows for fast and leak-tight assembly of compact cartridges with tightly spaced fluidic interconnects. The high sensitivity of the slot-waveguide resonators, combined with on-chip referencing and physical modelling, yields a volume refractive index detection limit of 5 x 10(-6) refractive index units (RIUs) and a surface mass density detection limit of 0.9 pg mm(-2), to our knowledge the best reported values for integrated planar ring resonators.
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| 5. |
- Giannone, Domenico, et al.
(författare)
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High Performance Multichannel Photonic Biochip Sensors for Future Point of Care Diagnostics : an Overview on Two EU-Sponsored Projects
- 2010
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Ingår i: SPIE Proc. 7715 BIOPHOTONICS - PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE II. - : SPIE. - 9780819481887 ; , s. 77150U-1-77150U-12
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Konferensbidrag (refereegranskat)abstract
- We present here research work on two optical biosensors which have been developed within two separate European projects (6(th) and 7(th) EU Framework Programmes). The biosensors are based on the idea of a disposable biochip, integrating photonics and microfluidics, optically interrogated by a multichannel interrogation platform. The objective is to develop versatile tools, suitable for performing screening tests at Point of Care or for example, at schools or in the field. The two projects explore different options in terms of optical design and different materials. While SABIO used Si(3)N(4)/SiO(2) ring resonators structures, P3SENS aims at the use of photonic crystal devices based on polymers, potentially a much more economical option. We discuss both approaches to show how they enable high sensitivity and multiple channel detection. The medium term objective is to develop a new detection system that has low cost and is portable but at the same time offering high sensitivity, selectivity and multiparametric detection from a sample containing various components (e. g. blood, serum, saliva, etc.). Most biological sensing devices already present on the market suffer from limitations in multichannel operation capability (either the detection of multiple analytes indicating a given pathology or the simultaneous detection of multiple pathologies). In other words, the number of different analytes that can be detected on a single chip is very limited. This limitation is a main issue addressed by the two projects. The excessive cost per test of conventional bio sensing devices is a second issue that is addressed.
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| 6. |
- Gylfason, Kristinn B., 1978-, et al.
(författare)
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A packaged optical slot-waveguide ring resonator sensor array for multiplex assays in labs-on-chip
- 2009
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Ingår i: Proceedings of Conference, MicroTAS 2009 - The 13th International Conference on Miniaturized Systems for Chemistry and Life Sciences. - : Chemical and Biological Microsystems Society. - 9780979806421 ; , s. 2004-2006
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Konferensbidrag (refereegranskat)abstract
- We present the design, fabrication, and characterization of a packaged array of individually addressable slot-waveguide ring resonator sensors in a compact cartridge for sensitive, label-free, multiplex assays. The novel use of a dual surfaceenergy adhesive film enables simple generic packaging method for multiple sensors in a single cartridge. The use of optical slot-waveguides, and drift compensation by on-chip light splitting to reference sensors, gives the best refractive-index limit of detection reported for planar ring resonator sensors.
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| 7. |
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| 8. |
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| 9. |
- Gylfason, Kristinn, 1978-, et al.
(författare)
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On-chip temperature compensation in an integrated slot-waveguide ring resonator refractive index sensor array
- 2010
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Ingår i: Optics Express. - 1094-4087. ; 18:4, s. 3226-3237
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Tidskriftsartikel (refereegranskat)abstract
- We present an experimental study of an integrated slot-waveguide refractive index sensor array fabricated in silicon nitride on silica. We study the temperature dependence of the slot-waveguide ring resonator sensors and find that they show a low temperature dependence of -16.6 pm/K, while at the same time a large refractive index sensitivity of 240 nm per refractive index unit. Furthermore, by using on-chip temperature referencing, a differential temperature sensitivity of only 0.3 pm/K is obtained, without individual sensor calibration. This low value indicates good sensor-to-sensor repeatability, thus enabling use in highly parallel chemical assays. We demonstrate refractive index measurements during temperature drift and show a detection limit of 8.8 x 10(-6) refractive index units in a 7 K temperature operating window, without external temperature control. Finally, we suggest the possibility of athermal slot-waveguide sensor design.
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| 10. |
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| 11. |
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| 12. |
- Kazmierczak, Andrzej, et al.
(författare)
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High quality optical microring resonators in Si3N 4/SiO2
- 2008
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Ingår i: Proceedings of the 14th European Conference on Integrated Optics - ECIO'08 Eindhoven. - 9789038613178 ; , s. 313-316
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Konferensbidrag (refereegranskat)abstract
- We have experimentally demonstrated high Q-factors strip waveguide resonators using the Si3N4/SiO2 material platform at the wavelength of 1.31μm. The analyzed filters demonstrate high quality factors reaching 133,000. The dependence on resonator radii and coupling gap is also discussed.
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| 13. |
- Kazmierczak, Andrzej, et al.
(författare)
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Light coupling and distribution for Si3N4/SiO2 integrated multichannel single-mode sensing system
- 2009
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Ingår i: Optical Engineering. - : SPIE-Intl Soc Optical Eng. - 0091-3286 .- 1560-2303. ; 48:1
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Tidskriftsartikel (refereegranskat)abstract
- We present an efficient and highly alignment-tolerant light coupling and distribution system for a multichannel Si3N4/SiO2 single-mode photonics sensing chip. The design of the input and output couplers and the distribution splitters is discussed. Examples of multichannel data obtained with the system are given.
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| 14. |
- Maire, Guillaume, et al.
(författare)
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High efficiency silicon nitride surface grating couplers
- 2008
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Ingår i: Optics Express. - 1094-4087. ; 16:1, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- High efficiency surface grating couplers for silicon nitride waveguides have been designed, fabricated, and characterized. Coupling efficiencies exceeding 60 % are reported at a wavelength of 1.31 mu m, as well as angular and wavelength -3 dB tolerances of 4 and 50 nm, respectively. When the wavelength is increased from 1310 nm to 1450 nm the coupling efficiency progressively decreases but remains above 20 % at 1450 nm. The influence of the duty ratio of the grating has also been investigated: maximum coupling efficiency was obtained at 50 % duty ratio.
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| 15. |
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| 16. |
- Sun, Xu, 1987-
(författare)
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Hybrid Plasmonic Devices for Optical Communication and Sensing
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hybrid plasmonic (HP) waveguides, a multi-layer waveguide structure supporting a hybrid mode of surface plasmonics and Si photonics, is a compromise way to integrate plasmonic materials into Si or SOI platforms, which can guide optical waves of sub-wavelength size, and with relative low propagation loss. In this thesis, several HP waveguides and devices are developed for the purposes of optical communications and sensing. The single-slot HP ring resonator sensor with 2.6µm radius can give a quality factor (Q factor) of 1300 at the communication wavelength of 1.5µm with a device sensitivity of 102nm/RIU (refractive index unit). The Mach-Zehnder interferometer (MZI) with a 40µm double-slot HP waveguide has a device sensitivity around 474nm/RIU. The partly open silicon side-coupled double-slot HP ring resonator has a device sensitivity of 687.5nm/RIU, with a Q factor over 1000 after optimization. Further, an all-optical switching HP donut resonator with a photothermal plasmonic absorber is developed, utilizing the thermal expansion effect of silicon to shift the resonant peak of the HP resonator. The active area has a radius of 10µm to match the core size of a single-mode fiber. By applying 10mW power of the driving laser to the absorber, the resonator transmitted power can be changed by 15dB, with an average response time of 16µs. Using the same fabrication flow, and removing the oxide materials using hydrogen fluoride wet etching, a hollow HP waveguide is fabricated for liquid sensing applications. The experimentally demonstrated waveguide sensitivity is about 0.68, which is more than twice that of pure Si waveguide device. Microelectromechanical systems (MEMS) can also be integrated into vertical HP waveguides. By tuning the thickness of the air gap, over 20dB transmitted power change was experimentally demonstrated. This can be used for optical switching applications by either changing the absorption or phase of the HP devices.
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| 17. |
- Trotta, Luca, et al.
(författare)
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Diagnostics of rare disorders : whole-exome sequencing deciphering locus heterogeneity in telomere biology disorders
- 2018
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Ingår i: Orphanet Journal of Rare Diseases. - : BioMed Central (BMC). - 1750-1172. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: The telomere biology disorders (TBDs) include a range of multisystem diseases characterized by mucocutaneous symptoms and bone marrow failure. In dyskeratosis congenita (DKQ, the clinical features of TBDs stem from the depletion of crucial stem cell populations in highly proliferative tissues, resulting from abnormal telomerase function. Due to the wide spectrum of clinical presentations and lack of a conclusive laboratory test it may be challenging to reach a clinical diagnosis, especially if patients lack the pathognomonic clinical features of TBDs.Methods: Clinical sequencing was performed on a cohort of patients presenting with variable immune phenotypes lacking molecular diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the absence of compelling diagnostic hints in patients with variable immunological and haematological conditions.Results: In four patients belonging to three families, we have detected five novel variants in known TBD-causing genes (DKC1, TERT and RTEL1). In addition to the molecular findings, they all presented shortened blood cell telomeres. These findings are consistent with the displayed TBD phenotypes, addressing towards the molecular diagnosis and subsequent clinical follow-up of the patients.Conclusions: Our results strongly support the utility of WES-based approaches for routine genetic diagnostics of TBD patients with heterogeneous or atypical clinical presentation who otherwise might remain undiagnosed.
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| 18. |
- Vivien, Laurent, et al.
(författare)
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A high efficiency silicon nitride grating coupler
- 2007
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Ingår i: 2007 4th IEEE International Conference on Group IV Photonics. - : IEEE. - 9781424409341 ; , s. 157-159
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Konferensbidrag (refereegranskat)abstract
- The experimental demonstration of a high efficiency silicon nitride grating coupler is reported for wavelengths from lambda=1.25 to 1.45 mu m for TE polarization. At the resonant angle, a coupling efficiency higher than 60% has been measured.
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| 19. |
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| 20. |
- Wang, Yuchen, et al.
(författare)
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Enhancing Si3N4 Waveguide Nonlinearity with Heterogeneous Integration of Few-Layer WS2
- 2021
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Ingår i: ACS Photonics. - : American Chemical Society (ACS). - 2330-4022. ; 8:9, s. 2713-2721
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Tidskriftsartikel (refereegranskat)abstract
- The heterogeneous integration of low-dimensional materials with photonic waveguides has spurred wide research interest. Here, we report on the experimental investigation and the numerical modeling of enhanced nonlinear pulse broadening in silicon nitride waveguides with the heterogeneous integration of few-layer WS2. After transferring a few-layer WS2 flake of similar to 14.8 mu m length, the pulse spectral broadening in a dispersion-engineered silicon nitride waveguide has been enhanced by similar to 48.8% in bandwidth. Through numerical modeling, an effective nonlinear coefficient higher than 600 m(-1) W-1 has been retrieved for the heterogeneous waveguide indicating an enhancement factor of larger than 300 with respect to the pristine waveguide at a wavelength of 800 nm. With further advances in two-dimensional material fabrication and integration techniques, on-chip heterostructures will offer another degree of freedom for waveguide engineering, enabling high-performance nonlinear optical devices, such as frequency combs and quantum light sources.
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