IRS-assisted vehicular visible light communications systems: channel modeling and performance analysis.

Visible light communications (VLC) is a promising solution as an alternative for the fully occupied radio frequency bands in the near future. The rear (tail) and front of vehicles have lamps that can be used for vehicular visible light communications (VVLC) systems. However, one of the main challenges of VLC systems is the line-of-sight (LoS) blockage issue. In this paper, we propose the installation of intelligent reflecting surfaces (IRSs) (i.e., smart mirrors) on the back of vehicles to overcome the issue in VVLC systems. We assume three different patterns of angular distribution for the radiation intensity: a commercially available LED with an asymmetrical pattern (Philips Luxeon Rebel), a symmetrical Lambertian pattern, and an asymmetrical Gaussian pattern. In the first section of this paper, we obtain the channel model for the IRS-assisted VVLC systems, then we investigate the path loss results versus link distance under different conditions such as weather type (clear, rainy, moderate fog, and thick fog) and radiation patterns. Moreover, the impact of system parameters such as the aperture size of the photodetector (PD), side-to-side and front-to-front distances, the number of IRS elements, and the IRS area are studied. In the second part, we derive a closed-form expression for the maximum achievable link distance versus the probability of error for the IRS-assisted VVLC systems. In addition, in this section we analyze the impact of the parameters in a single-photon avalanche diode (SPAD), background noise, and the system parameters for the path loss.

Performance of quantum-dash mode-locked lasers (QD-MLLDs) for high-capacity coherent optical communications.

We investigate the capabilities and limitations of quantum-dash mode-locked lasers (QD-MLLDs) as optical frequency comb sources in coherent optical communication systems. We demonstrate that QD-MLLDs are on par with conventional single-wavelength narrow linewidth laser sources and can support high symbol rates and modulation formats. We manage to transmit 64 quadrature amplitude modulation (QAM) signals up to 80 GBd over 80 km of standard single-mode fiber (SSMF), which highlights the distinctive phase noise performance of the QD-MLLD. Using a 38.5 GHz (6 dB bandwidth) silicon photonic (SiP) modulator, we achieve a maximum symbol rate of 104 GBd with 16QAM signaling and a maximum net rate of 416 Gb/s per carrier in a single polarization setup and after 80 km-SSMF transmission. We also compare QD-MLLD performance with commercial narrow-linewidth integrable tunable laser assemblies (ITLAs) and explore their potential for use as local oscillators (LOs) and signal carriers. The QD-MLLD has 45 comb lines usable for transmission at a frequency spacing of 25 GHz, and an RF linewidth of 35 kHz.

Photonic beamforming using a quantum-dash optical frequency comb source.

We demonstrate photonic beamforming using a quantum-dash (QD) optical frequency comb (OFC) source. Thanks to the 25 GHz free spectral range (FSR) and up to 40 comb lines available from the QD OFC, we can implement phased antenna arrays (PAAs) with directional radiation and scanning. We consider two types of PAAs: a uniform linear array (ULA) and a uniform planar array (UPA). By selecting different comb lines with a programmable optical filter, we can tune the FSR of the OFC source and realize a discrete scanning function. We evaluate the beam squint of the ULAs, and the results show that we can achieve broadband operation. Finally, we show that we can achieve both directional radiation and scanning simultaneously using the UPA.

Independent Prediction of Child Psychiatric Symptoms by Maternal Mental Health and Child Polygenic Risk Scores.

OBJECTIVE: Prenatal maternal symptoms of depression and anxiety are associated with an increased risk for child socioemotional and behavioral difficulties, supporting the fetal origins of mental health hypothesis. However, to date, studies have not considered specific genomic risk as a possible confound. METHOD: The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 5,546) was used to test if child polygenic risk score for attention-deficit/hyperactivity disorder (ADHD), schizophrenia, or depression confounds or modifies the impact of prenatal maternal depression and anxiety on child internalizing, externalizing, and total emotional/behavioral symptoms from age 4 to 16 years. Longitudinal child and adolescent symptom data were analyzed in the ALSPAC cohort using generalized estimating equations. Replication analyses were done in an independent cohort (Prevention of Preeclampsia and Intrauterine Growth Restriction [PREDO] cohort; n = 514) from Finland, which provided complementary measures of maternal mental health and child psychiatric symptoms. RESULTS: Maternal depression and anxiety and child polygenic risk scores independently and additively predicted behavioral and emotional symptoms from childhood through mid-adolescence. There was a robust prediction of child and adolescent symptoms from both prenatal maternal depression (generalized estimating equation estimate = 0.093, 95% CI 0.065-0.121, p = 2.66 × 10-10) and anxiety (generalized estimating equation estimate = 0.065, 95% CI 0.037-0.093, p = 1.62 × 10-5) after adjusting for child genomic risk for mental disorders. There was a similar independent effect of maternal depression (B = 0.156, 95% CI 0.066-0.246, p = .001) on child symptoms in the PREDO cohort. Genetically informed sensitivity analyses suggest that shared genetic risk only partially explains the reported association between prenatal maternal depression and offspring mental health. CONCLUSION: These findings highlight the genomic contribution to the fetal origins of mental health hypothesis and further evidence that prenatal maternal depression and anxiety are robust in utero risks for child and adolescent psychiatric symptoms.

Disease-specific selective vulnerability and neuroimmune pathways in dementia revealed by single cell genomics.

The development of successful therapeutics for dementias requires an understanding of their shared and distinct molecular features in the human brain. We performed single-nuclear RNAseq and ATACseq in Alzheimer disease (AD), Frontotemporal degeneration (FTD), and Progressive Supranuclear Palsy (PSP), analyzing 40 participants, yielding over 1.4M cells from three brain regions ranging in vulnerability and pathological burden. We identify 35 shared disease-associated cell types and 14 that are disease-specific, replicating those previously identified in AD. Disease - specific cell states represent molecular features of disease-specific glial-immune mechanisms and neuronal vulnerability in each disorder, layer 4/5 intra-telencephalic neurons in AD, layer 2/3 intra-telencephalic neurons in FTD, and layer 5/6 near-projection neurons in PSP. We infer intrinsic disease-associated gene regulatory networks, which we empirically validate by chromatin footprinting. We find that causal genetic risk acts in specific neuronal and glial cells that differ across disorders, primarily non-neuronal cells in AD and specific neuronal subtypes in FTD and PSP. These data illustrate the heterogeneous spectrum of glial and neuronal composition and gene expression alterations in different dementias and identify new therapeutic targets by revealing shared and disease-specific cell states.

Encryption in phase space for classical coherent optical communications.

Optical layer attacks on optical fiber communication networks are one of the weakest reinforced areas of the network, allowing attackers to overcome security software or firewalls when proper safeguards are not put into place. Encrypting data using a random phase mask is a simple yet effective way to bolster the data security at the physical layer. Since the interactions of the random phases used for such encryption heavily depend on system properties like data rate, modulation format, distance, degree of phase randomness, laser properties, etc., it is important to determine the optimum operating conditions for different scenarios. In this work, assuming that the transmitter and the receiver have a secret pre-shared key, we present a theoretical study of security in such a system through mutual information analysis. Next, we determine operating conditions which ensure security for 4-PSK, 16-PSK, and 128-QAM formats through numerical simulation. Moreover, we provide an experimental demonstration of the system using 16-QAM modulation. We then use numerical simulation to verify the efficacy of the encryption and study two preventative measures for different modulation formats which will prevent an eavesdropper from obtaining any data. The results demonstrate that the system is secure against a tapping attack if an attacker has no information of the phase modulator and pre-shared key.

AL-aided AMC in a multi-user white-light OFDMA VLC system over a light-diffusing fiber loop.

To develop an adaptive modulation scheme for flexible high-speed multi-user visible light communication (VLC), automatic modulation classification (AMC) is adopted for monitoring the modulation formats of different subcarrier groups. An AMC scheme based on a joint convolutional neural network (CNN), active learning (AL), and data augmentation (DA) is demonstrated over an orthogonal frequency division multiplexing access (OFDMA) VLC system. The configuration of the diffuse white-light VLC system is combined with a pair integrated transceiver module, a light-diffusing fiber (LDF), and a wireless channel, which can provide white-light illumination and ubiquitous access. Within the forward error correction (FEC) threshold, the data rates of the white-light VLC links can reach 325.5 Mbps with a bit error rate (BER) of 2.163 × 10-3. An experiment with two-user access via the proposed VLC link with an unequal bandwidth allocation was demonstrated. The performance of the AL-aided CNN AMC scheme also shows a classification accuracy rate of 95.48% for the constellation diagrams of different subcarriers of the OFDMA signal over 240 training samples and faster convergence than a CNN-based AMC.

EZH2 Methyltransferase Regulates Neuroinflammation and Neuropathic Pain.

Recent studies by us and others have shown that enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, in glial cells regulates the genesis of neuropathic pain by modulating the production of proinflammatory cytokines and chemokines. In this review, we summarize recent advances in this research area. EZH2 is a subunit of polycomb repressive complex 2 (PRC2), which primarily serves as a histone methyltransferase to catalyze methylation of histone 3 on lysine 27 (H3K27), ultimately resulting in transcriptional repression. Animals with neuropathic pain exhibit increased EZH2 activity and neuroinflammation of the injured nerve, spinal cord, and anterior cingulate cortex. Inhibition of EZH2 with DZNep or GSK-126 ameliorates neuroinflammation and neuropathic pain. EZH2 protein expression increases upon activation of Toll-like receptor 4 and calcitonin gene-related peptide receptors, downregulation of miR-124-3p and miR-378 microRNAs, or upregulation of Lncenc1 and MALAT1 long noncoding RNAs. Genes suppressed by EZH2 include suppressor of cytokine signaling 3 (SOCS3), nuclear factor (erythroid-derived 2)-like-2 factor (NrF2), miR-29b-3p, miR-146a-5p, and brain-specific angiogenesis inhibitor 1 (BAI1). Pro-inflammatory mediators facilitate neuronal activation along pain-signaling pathways by sensitizing nociceptors in the periphery, as well as enhancing excitatory synaptic activities and suppressing inhibitory synaptic activities in the CNS. These studies collectively reveal that EZH2 is implicated in signaling pathways known to be key players in the process of neuroinflammation and genesis of neuropathic pain. Therefore, targeting the EZH2 signaling pathway may open a new avenue to mitigate neuroinflammation and neuropathic pain.

Genetic predisposition to depression and inflammation impacts symptom burden and survival in patients with head and neck cancer: A longitudinal study.

OBJECTIVE: The primary purpose of this study was to investigate the contribution of genetic predispositions to depression and inflammation, as measured through polygenic risk scores, on symptom burden (physical and psychological) in patients with head and neck cancer in the immediate post-treatment period (i.e., at three months post-diagnosis), as well as on 3-, 6-, 12-, 24- and 36-month survival. METHODS: Prospective longitudinal study of 223 adults (72 % participation) newly diagnosed with a first occurrence of primary head and neck cancer, paired with genetic data (Illumina PsychArray), validated psychometric measures, Structured Clinical Interviews for DSM Disorders (SCID-I), and medical chart reviews. RESULTS: Symptom burden at 3 months was predicted by (R2 adj. = 0.38, p < 0.001): a baseline SCID-I Anxiety Disorder (b = 1.69, B = 0.23, 95%CI = 0.43-2.94; p = 0.009), baseline levels of HADS anxiety (b = 0.20, B = 0.29, 95%CI = 0.07-0.34; p = 0.003), the polygenic risk score (PRS) for depression (b = 0.66, B = 0.18, 95%CI = 0.003-1.32; p = 0.049), and cumulated dose of radiotherapy (b = 0.002, B = 0.46, 95%CI = 0.001-0.003; p < 0.001). When controlling for factors known to be associated with cancer survival, patients with a higher PRS associated with depression and inflammation, respectively, presented higher risk of death within 36 months (b = 1.75, Exp(B) = 5.75, 95%CI = 1.55-21.27, p = 0.009 and b = 0.14, Exp(B) = 1.15, 95%CI = 1.01-1.30, p = 0.03). CONCLUSIONS: Our results outline three potential pathways of symptom burden in patients with head and neck cancer: a genetic predisposition towards depression; an initial anxiety disorder upon being diagnosed with cancer or high levels of anxiety upon diagnosis; and a dose-related response to radiotherapy. One may want to investigate early interventions in these areas to alleviate symptom burden in patients faced with a life-threatening disease, as well as consider targeting genetic predisposition towards depression and inflammation implicated in survival. The high prevalence of distress in patients with head and neck cancer is an opportunity to study genetic predispositions, which could potentially be broadly generalized to other cancers and diseases.

Polarization independent Bragg gratings using tilted subwavelength grating waveguide Bragg gratings.

We propose and experimentally demonstrate a polarization independent subwavelength grating (SWG) waveguide Bragg grating (WBG) by using an SWG waveguide with tilted segments. By optimizing the tilting angle and other geometry parameters, such as the width and the length of the loading segments used to create the BG, we can obtain a zero birefringence tilted SWG waveguide and consequently, a polarization independent SWG WBG. In our simulations, the optimal tilting angle is ∼ 58°, whereas the optimal angle obtained in fabrication is ∼ 46°. This deviation is mainly due to fabrication errors, e.g., on the sidewall angle of the silicon segments. For the optimal tilting angle of 46°, the characterized Bragg wavelengths of the TE and TM modes are both ∼ 1517 nm. We believe that the proposed device can have applications in optical communications and interconnections.

Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain.

Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions. GPR109A, a Gi protein-coupled receptor, has emerged as an important therapeutic target for controlling inflammation in various tissues and organs. In this review, we summarized current data about the role of GPR109A in neuroinflammation. Specifically, we focused on the pharmacological features of GPR109A and signaling pathways used by GPR109A to ameliorate neuroinflammation and symptoms in Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and pathological pain conditions.

Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation.

Pentameric ligand-gated ion channels (pLGICs) mediate synaptic transmission and are sensitive to their lipid environment. The mechanism of phospholipid modulation of any pLGIC is not well understood. We demonstrate that the model pLGIC, ELIC (Erwinia ligand-gated ion channel), is positively modulated by the anionic phospholipid, phosphatidylglycerol, from the outer leaflet of the membrane. To explore the mechanism of phosphatidylglycerol modulation, we determine a structure of ELIC in an open-channel conformation. The structure shows a bound phospholipid in an outer leaflet site, and structural changes in the phospholipid binding site unique to the open-channel. In combination with streamlined alchemical free energy perturbation calculations and functional measurements in asymmetric liposomes, the data support a mechanism by which an anionic phospholipid stabilizes the activated, open-channel state of a pLGIC by specific, state-dependent binding to this site.

Electrically reconfigurable waveguide Bragg grating filters.

We propose and demonstrate an electrically reconfigurable waveguide Bragg grating filters in silicon-on-insulator using a multiple-contact heater element. There are six electrical pads connected to the heater element in an equidistant manner. These electrical pads allow to create different heat, and corresponding refractive index, distributions across the grating so that the local Bragg wavelength corresponding to the heated segments can be controlled. In turn, this control over the heat distribution allows the device to be reconfigured to implement different filter spectral responses. These filters are applicable for both wavelength division multiplexing systems and optical signal processing applications. As a verification, we demonstrate the generation of two (or more) separate filter bands with a spacing up to 35 nm or a Fabry-Pérot cavity with a 1.6 nm free-spectral range. Moreover, we explain a firm and accurate simulation framework of the proposed device based on COMSOL Multiphysics and the transfer matrix method, which is in excellent agreement with our experimental measurements.

Cysteine metabolic engineering and selective disulfide reduction produce superior antibody-drug-conjugates.

Next-generation site-specific cysteine-based antibody-drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation requires complex full reduction and reoxidation processes, impacting product quality. To overcome this technical challenge, we developed a novel antibody manufacturing process through cysteine (Cys) metabolic engineering in Chinese hamster ovary cells implementing a unique cysteine-capping technology. This development enabled a direct conjugation of drugs after chemoselective-reduction with mild reductant tris(3-sulfonatophenyl)phosphine. This innovative platform produces clinical ADC products with superior quality through a simplified manufacturing process. This technology also has the potential to integrate Cys-based site-specific conjugation with other site-specific conjugation methodologies to develop multi-drug ADCs and exploit multi-mechanisms of action for effective cancer treatments.

Reconfigurable microwave photonic filter based on a quantum dash mode-locked laser.

We demonstrate a reconfigurable microwave photonic (MWP) filter using a quantum dash (QDash) mode-locked laser (MLL) that can generate an optical frequency comb (OFC) with ∼50 comb lines and a free spectral range of 25 GHz. Thanks to the large number of comb lines, the MWP filter responses can be easily programmed by tailoring the OFC spectrum. We implement MWP filter responses with Gaussian, sinc, flat-top, and multiple peaks, as well as demonstrate that tuning of the central frequency. We achieve a minimum 3 dB bandwidth of ∼100 MHz for a sinc-shaped MWP filter, while the maximum out-of-band rejection can be up to ∼30 dB with Gaussian apodization. Our results show that the QDash-MLL is a promising OFC source for developing integrated and reconfigurable MWP filters.

Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites.

Polyunsaturated fatty acids (PUFAs) inhibit pentameric ligand-gated ion channels (pLGICs) but the mechanism of inhibition is not well understood. The PUFA, docosahexaenoic acid (DHA), inhibits agonist responses of the pLGIC, ELIC, more effectively than palmitic acid, similar to the effects observed in the GABAA receptor and nicotinic acetylcholine receptor. Using photo-affinity labeling and coarse-grained molecular dynamics simulations, we identified two fatty acid binding sites in the outer transmembrane domain (TMD) of ELIC. Fatty acid binding to the photolabeled sites is selective for DHA over palmitic acid, and specific for an agonist-bound state. Hexadecyl-methanethiosulfonate modification of one of the two fatty acid binding sites in the outer TMD recapitulates the inhibitory effect of PUFAs in ELIC. The results demonstrate that DHA selectively binds to multiple sites in the outer TMD of ELIC, but that state-dependent binding to a single intrasubunit site mediates DHA inhibition of ELIC.

Early Life Adversity and Polygenic Risk for High Fasting Insulin Are Associated With Childhood Impulsivity.

While the co-morbidity between metabolic and psychiatric behaviors is well-established, the mechanisms are poorly understood, and exposure to early life adversity (ELA) is a common developmental risk factor. ELA is associated with altered insulin sensitivity and poor behavioral inhibition throughout life, which seems to contribute to the development of metabolic and psychiatric disturbances in the long term. We hypothesize that a genetic background associated with higher fasting insulin interacts with ELA to influence the development of executive functions (e.g., impulsivity in young children). We calculated the polygenic risk scores (PRSs) from the genome-wide association study (GWAS) of fasting insulin at different thresholds and identified the subset of single nucleotide polymorphisms (SNPs) that best predicted peripheral insulin levels in children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort [N = 467; p t- initial = 0.24 (10,296 SNPs), p t- refined = 0.05 (57 SNPs)]. We then calculated the refined PRS (rPRS) for fasting insulin at this specific threshold in the children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort and investigated its interaction effect with adversity on an impulsivity task applied at 36 months. We found a significant effect of interaction between fasting insulin rPRS and adversity exposure predicting impulsivity measured by the Snack Delay Task at 36 months [ß = -0.329, p = 0.024], such that higher PRS [ß = -0.551, p = 0.009] was linked to more impulsivity in individuals exposed to more adversity. Enrichment analysis (MetaCoreTM) of the SNPs that compose the fasting insulin rPRS at this threshold was significant for certain nervous system development processes including dopamine D2 receptor signaling. Additional enrichment analysis (FUMA) of the genes mapped from the SNPs in the fasting insulin rPRS showed enrichment with the accelerated cognitive decline GWAS. Therefore, the genetic background associated with risk for adult higher fasting insulin moderates the impact of early adversity on childhood impulsivity.

Bacterial Quorum Sensing Signals Promote Large-Scale Remodeling of Lipid Membranes.

We report that N-acyl-l-homoserine lactones (AHLs), a class of nonionic amphiphiles that common bacteria use as signals to coordinate group behaviors, can promote large-scale remodeling in model lipid membranes. Characterization of supported lipid bilayers (SLBs) of the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) by fluorescence microscopy and quartz crystal microbalance with dissipation (QCM-D) reveals the well-studied AHL signal 3-oxo-C12-AHL and its anionic head group hydrolysis product (3-oxo-C12-HS) to promote the formation of long microtubules that can retract into hemispherical caps on the surface of the bilayer. These transformations are dynamic, reversible, and dependent upon the head group structure. Additional experiments demonstrate that 3-oxo-C12-AHL can promote remodeling to form microtubules in lipid vesicles and promote molecular transport across bilayers. Molecular dynamics (MD) simulations predict differences in thermodynamic barriers to translocation of these amphiphiles across a bilayer that are reflected in both the type and extent of reformation and associated dynamics. Our experimental observations can thus be interpreted in terms of accumulation and relief of asymmetric stresses in the inner and outer leaflets of a bilayer upon intercalation and translocation of these amphiphiles. Finally, experiments on Pseudomonas aeruginosa, a pathogen that uses 3-oxo-C12-AHL for cell-to-cell signaling, demonstrate that 3-oxo-C12-AHL and 3-oxo-C12-HS can promote membrane remodeling at biologically relevant concentrations and in the absence of other biosurfactants, such as rhamnolipids, that are produced at high population densities. Overall, these results have implications for the roles that 3-oxo-C12-AHL and its hydrolysis product may play in not only mediating intraspecies bacterial communication but also processes such as interspecies signaling and bacterial control of host-cell response. Our findings also provide guidance that could prove useful for the design of synthetic self-assembled materials that respond to bacteria in ways that are useful in the context of sensing, drug delivery, and in other fundamental and applied areas.

Dual-frequency optoelectronic oscillator incorporating a single cavity and multiband microwave photonic filter.

Dual-frequency optoelectronic oscillators (OEOs) have potential applications in dual-band wireless networking and dual-parameter sensing systems. We propose a dual-frequency OEO incorporating a multiband microwave photonic filter (MPF). In particular, the two microwave signals are generated simultaneously in a single OEO cavity. By simply varying the parameters of optical spectral slicing and sampling (e.g., with a programmable optical filter) used to implement the MPF, we can readily achieve simultaneous tuning of the dual-frequency output, as well as alternate switching between single-frequency and dual-frequency output. The multi-passband nature of the MPF, enabled via optical spectral slicing, opens a path to multi-frequency OEO operation by scaling our scheme in the future. Such a structure provides a flexible way to generate simultaneously tunable and reconfigurable multi-frequency microwave signals.

On-chip optical true time delay lines based on subwavelength grating waveguides.

An optical true time delay line (OTTDL) is a fundamental building block for signal processing applications in microwave photonics and optical communications. Here, we experimentally demonstrate an index-variable OTTDL based on an array of 40 subwavelength grating (SWG) waveguides in silicon-on-insulator. Each SWG waveguide in the array is 34 mm long and arranged in a serpentine manner; the average incremental delay between waveguides is about 4.7 ps, and the total delay between the first and last waveguides is approximately 181.9 ps. The waveguide array occupies a chip area of ∼6.5mm×8.7mm=56.55mm2. The proposed OTTDLs bring potential advantages in terms of compactness as well as operation versatility to a variety of microwave signal processing applications.