Fast path and polarisation manipulation of telecom wavelength single photons in lithium niobate waveguide devices

We demonstrate fast polarisation and path control of photons at 1550 nm in lithium niobate waveguide devices using the electro-optic effect. We show heralded single photon state engineering, quantum interference, fast state preparation of two entangled photons and feedback control of quantum interference. These results point the way to a single platform that will enable the integration of nonlinear single photon sources and fast reconfigurable circuits for future photonic quantum information science and technology.Comment: 6 page

GABA and glycine immunoreactivity in the guinea pig superior olivary complex

Immunoperoxidase immunocytochemistry was employed to examine the distribution of [gamma]-aminobutyric acid (GABA)- and glycine (GLY)-immunoreactive cells, fibers, and terminals in the guinea pig superior olivary complex. The nuclei studied were the lateral superior olive (LSO), medial superior olive (MSO), superior paraolivary nucleus (SPN), and the medial, ventral, and lateral nuclei of the trapezoid body (MNTB, VNTB, and LNTB, respectively). The majority of LSO neurons exhibited GABA-immunoreactive (+) labeling. These same neurons were also lightly GLY+. Extensive perisomatic punctate GLY+ labeling was ovserved on most LSO neurons; these puncta most likely correspond to synaptic terminals. A very small number of MSO fusiform neurons were GABA+, and none were GLY+. The GLY positive perisomatic punctate labeling around most MSO neurons, although abundant, was not as profuse as that observed in the LSO. The MNTB neurons corresponding to the principal and elongate types were intensely GLY+ and were contacted by small numbers of GLY+ puncta. There was extensive GLY+ punctate labeling in the SPN that surrounded the cell bodies of most of its large, radiate neurons and many of the smaller, fusiform neurons. The few large, radiate neurons that were lightly GLY+ possessed far fewer GLY+ puncta on their perikarya. The distribution of GABA+ puncta was generally diffuse and scattered throughout the nuclei described above. In the VNTB and LNTB, several large neurons of various shapes were GLY+ as were the small, oval neurons. The extent of GLY+ punctate labeling was quite variable in both nuclei. The majority of perikarya in the VNTB and LNTB were GABA+. A light distribution of GABA+ puncta was observed on most cell bodies in both nuclei. Peridendritic GABA+ punctate labeling was dense in the VNTB neuropil. Two small populations of GLY+ neurons were observed outside of the named nuclei of the SOC; one was located dorsal to the LSO, near its dorsal hilus, and the other was identified near the medial pole of the LSO. The somata of both populations possessed extremely sparse GLY+ punctate labeling. In general, these results agree with and expand on findings in rodents from previous studies. There appears, however, to be differences between the guinea pig and cat with regard to the proportions of GABA+ neurons in the LSO and GLY+ punctate labeling in the MSO.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27689/1/0000073.pd

Gallium Arsenide (GaAs) Quantum Photonic Waveguide Circuits

Integrated quantum photonics is a promising approach for future practical and large-scale quantum information processing technologies, with the prospect of on-chip generation, manipulation and measurement of complex quantum states of light. The gallium arsenide (GaAs) material system is a promising technology platform, and has already successfully demonstrated key components including waveguide integrated single-photon sources and integrated single-photon detectors. However, quantum circuits capable of manipulating quantum states of light have so far not been investigated in this material system. Here, we report GaAs photonic circuits for the manipulation of single-photon and two-photon states. Two-photon quantum interference with a visibility of 94.9 +/- 1.3% was observed in GaAs directional couplers. Classical and quantum interference fringes with visibilities of 98.6 +/- 1.3% and 84.4 +/- 1.5% respectively were demonstrated in Mach-Zehnder interferometers exploiting the electro-optic Pockels effect. This work paves the way for a fully integrated quantum technology platform based on the GaAs material system.Comment: 10 pages, 4 figure

High-extinction ratio integrated photonic filters for silicon quantum photonics

We present the generation of quantum-correlated photon pairs and subsequent pump rejection across two silicon-on-insulator photonic integrated circuits. Incoherently cascaded lattice filters are used to provide over 100 dB pass-band to stop-band contrast with no additional external filtering. Photon pairs generated in a microring resonator are successfully separated from the input pump, confirmed by a temporal correlations measurements

Multi-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut-brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD

Different Effect of Proteasome Inhibition on Vesicular Stomatitis Virus and Poliovirus Replication

Proteasome activity is an important part of viral replication. In this study, we examined the effect of proteasome inhibitors on the replication of vesicular stomatitis virus (VSV) and poliovirus. We found that the proteasome inhibitors significantly suppressed VSV protein synthesis, virus accumulation, and protected infected cells from toxic effect of VSV replication. In contrast, poliovirus replication was delayed, but not diminished in the presence of the proteasome inhibitors MG132 and Bortezomib. We also found that inhibition of proteasomes stimulated stress-related processes, such as accumulation of chaperone hsp70, phosphorylation of eIF2α, and overall inhibition of translation. VSV replication was sensitive to this stress with significant decline in replication process. Poliovirus growth was less sensitive with only delay in replication. Inhibition of proteasome activity suppressed cellular and VSV protein synthesis, but did not reduce poliovirus protein synthesis. Protein kinase GCN2 supported the ability of proteasome inhibitors to attenuate general translation and to suppress VSV replication. We propose that different mechanisms of translational initiation by VSV and poliovirus determine their sensitivity to stress induced by the inhibition of proteasomes. To our knowledge, this is the first study that connects the effect of stress induced by proteasome inhibition with the efficiency of viral infection

CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum

Purpose: Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD). Methods: Through international collaboration we collected data from 39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function. Results: The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits. Conclusion: We significantly broaden the mutational and clinical spectrum of CTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.Peer reviewe

Divergent Immune Responses in Behaviorally-Inhibited vs. Non-Inhibited Male Rats

Stable behavioral traits (temperament, personality) often predict health outcomes. Temperament-specific differences in immune function could explain temperament-specific health outcomes, however, we have limited information on whether immune function varies by personality. In the present study, we examined the relationship between a basic behavioral trait (behavioral-inhibition vs. non-inhibition) and two immune responses (innate inflammation and delayed-type hypersensitivity, DTH) in a rodent model. In humans, behavioral inhibition (fearful temperament) is associated with altered stress physiology and allergies. In laboratory rats, the trait is associated with elevated glucocorticoid production. We hypothesized that behavioral inhibition is associated with glucocorticoid resistance and dampened T-helper 1 cell responses often associated with chronic stress and allergies. Further, this immune profile would predict poorly-regulated innate inflammation and dampened DTH. In male Sprague-Dawley rats, we quantified consistent behavioral phenotypes by measuring latency to contact two kinds of novelty (object vs. social), then measured lipopolysaccharide(LPS)-induced innate inflammation or keyhole limpet hemocyanin(KLH)-induced DTH. Behaviorally-inhibited rats had heightened glucocorticoid and interleukin-6 responses to a low/moderate dose of LPS and reduced DTH swelling to KLH re-exposure compared to non-inhibited rats. These results suggest that behavioral inhibition is associated with a glucocorticoid resistant state with poorly regulated innate inflammation and dampened cell-mediated immune responses. This immune profile may be associated with exaggerated T-helper 2 responses, which could set the stage for an allergic/asthmatic/atopic predisposition in inhibited individuals. Human and animal models of temperament-specific immune responses represent an area for further exploration of mechanisms involved in individual differences in health

Rare pathogenic variants in WNK3 cause X-linked intellectual disability

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordData availability: All data are available upon request. The sequence variants in WNK3 (NM_004656.3) reported in the paper have been deposited in ClinVar database. Their respective accession numbers (SCV002107163 to SCV002107168) are indicated in Tables 1 and S1.Purpose WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. Method We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). Results We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had identifier with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. Conclusion Pathogenic WNK3 variants cause a rare form of human X-linked identifier with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism.Estonian Research CouncilNational Natural Science Foundation of ChinaRoyal SocietySouth Carolina Department of Disabilities and Special Needs (SCDDSN)National Institute of Neurological Disorders and Stroke (NINDS