Surface acoustic waves for acousto-optic modulation in buried silicon nitride waveguides

We theoretically investigate the use of Rayleigh surface acoustic waves (SAWs) for refractive index modulation in optical waveguides consisting of amorphous dielectrics. Considering low-loss Si 3 N 4 waveguides with a standard core cross section of 4.4× 0.03 μ m 2 size, buried 8 μ m deep in a SiO 2 cladding we compare surface acoustic wave generation in various different geometries via a piezo-active, lead zirconate titanate film placed on top of the surface and driven via an interdigitized transducer (IDT). Using numerical solutions of the acoustic and optical wave equations, we determine the strain distribution of the SAW under resonant excitation. From the overlap of the acoustic strain field with the optical mode field we calculate and maximize the attainable amplitude of index modulation in the waveguide. For the example of a near-infrared wavelength of 840 nm, a maximum shift in relative effective refractive index of 0.7x10 −3 was obtained for TE polarized light, using an IDT period of 30 - 35 μ m, a film thickness of 2.5 - 3.5 μ m, and an IDT voltage of 10 V. For these parameters, the resonant frequency is in the range 70 - 85 MHz. The maximum shift increases to 1.2x10 −3 , with a corresponding resonant frequency of 87 MHz, when the height of the cladding above the core is reduced to 3 μ m. The relative index change is about 300-times higher than in previous work based on non-resonant proximity piezo-actuation, and the modulation frequency is about 200-times higher. Exploiting the maximum relative index change of 1.2× 10 −3 in a low-loss balanced Mach-Zehnder modulator should allow full-contrast modulation in devices as short as 120 μ m (half-wave voltage length product = 0.24 Vcm)

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

On-chip optical isolator using surface acoustic wave

A major issue in integrated optics is the protection of on-chip lasers against undesired external feedback. In non-integrated systems, undesired reflections can be easily blocked using Faraday isolators. However, Faraday isolators require magneto-optic materials, which are difficult to integrate into compact devices. Yu and Fan [1] have proposed a non-magnetic integrated isolator, in which a transverse mode of an optical waveguide is converted to another transverse mode only for a single propagation direction. However, the best implementation so far [2], based on a transversely non-uniform index modulation in a semiconductor, showed high losses. We present a novel design to achieve such a modulation in lowloss dielectric waveguides, using surface acoustic waves. We theoretically describe how to realize the two most essential features, which are a short interaction length and a wide isolation bandwidth.