Multi-subcarrier (MSC) modulation is recently standing out as a notable new feature in the latest generations of high-speed coherent optical transceivers, providing distinctive advantages over legacy ...single-carrier systems. However, the transition from single-carrier to MSC modulation still requires significant optimization of digital signal processing subsystems, in order to maximize the inherent potential of subcarrier multiplexing. In this article, the penalty associated with the usage of carrier phase estimation (CPE) methods inherited from single-carrier systems is quantitatively studied and the need for enhanced MSC-tailored solutions is evidenced. A novel pilot-based joint-subcarrier CPE method based on a dual-reference subcarrier (DRS) approach is described and numerically assessed. The proposed DRS-CPE exploits the frequency-dependent walk-off effect imposed by chromatic dispersion (CD) to enable the separation of phase noise processes incurred by the transmitter and local oscillator lasers, thereby allowing to effectively apply joint-subcarrier CPE independently of the symbol-rate per subcarrier. Our numerical results demonstrate that the proposed DRS-CPE enables to operate with near-optimum performance at symbol-rates per subcarrier as low as 1 Gbaud over ultra-long-haul distances.
The tight channel filtering imposed by long cascades of reconfigurable optical add-drop multiplexers (ROADMs) represents, nowadays, one of the major performance-limiting aspects for optically-routed ...coherent optical fiber systems. This makes it vital to perform a ROADM-aware optimization of the network performance at the physical layer. In particular, the use of different modulation options is known to have a strong impact on the extent of the filtering-induced penalties. In that regard, a long debate between single- and multi-carrier modulation has been taking place during the last few years, sometimes leading to apparently contradictory results. Following the open scientific discussion on this topic, in this work, we investigate by simulation and experimentally the wavelength selective switch (WSS) filtering tolerance of single-carrier (SC) and digital subcarrier multiplexing (DSCM) signals. In order to promote a fair comparison, both modulation options are carefully designed to minimize the ROADM-filtering penalties, namely resorting to the use of entropy loading together with baud rate optimization. After some preliminary numerical assessment, a comprehensive set of experiments are carried out for the transmission of 21-WDM 95-105 Gbaud SC and DSCM signals over a 2040 km straight line of fiber with regularly spaced WSSs. In general, our results allow to conclude that the two modulation options yield similar performance if the overall baud rate is optimized for each filtering scenario, keeping the baud rate at <inline-formula><tex-math notation="LaTeX">\pm</tex-math></inline-formula>5% of the optimized value.
Digital subcarrier multiplexing (SCM) has recently emerged as a promising solution for next-generation ultra-high-baudrate coherent optical communication systems. Among its distinctive advantages ...over traditional single-carrier modulation, SCM enables the exploitation of symbol-rate optimization (SRO), which has been shown to enable the passive mitigation of the nonlinear interference noise (NLIN) that is generated during propagation over dispersion-unmanaged optical fiber systems. However, the full exploitation of SRO-based NLIN mitigation is severely hindered by the uncompensated distortion caused by laser phase noise (LPN) and non-linear phase noise (NLPN), whose impact is magnified by the use of low-baudrate subcarriers. Resorting to low-complexity carrier phase estimation (CPE) algorithms, in this paper we experimentally demonstrate that it is possible to overcome the hurdles posed by LPN and NLPN in SCM systems, provided that adequate joint-subcarrier CPE processing is employed. A dual-stage joint-processing approach composed of a pilot-based CPE optionally followed by a blind phase search (BPS)-based estimator is implemented and experimentally assessed, enabling to effectively optimize the symbol-rate per subcarrier down to 3 GBaud, in accordance with the theoretical SRO predictions for the system under test. In addition, we demonstrate that signal-to-noise ratio (SNR) gains of more than 1 dB can be achieved through joint-subcarrier CPE processing in shorter-reach links, while this gain tends to progressively reduce with increasing propagation distance, down to about 0.5 dB gain after 3000 km propagation.
Carrier phase recovery (CPR) is a key digital signal processing (DSP) subsystem in optical fiber communications. In this paper, we review recent advances in CPR algorithms and analyze their ...performance under the impact of different system impairments in a long-haul 256 GBaud setting. We study both single- and dual-stage CPR configurations, in the linear and nonlinear regimes, and at different system baud rates. By exploiting CPR algorithms tailored for digital subcarrier multiplexing (DSCM) systems, we are able to reap the benefits of their intrinsic resilience to the two main performance-limiting effects of optical fiber systems: equalization enhanced phase noise (EEPN) and nonlinear interference (NLI). Overall, the paper sheds light on the potential benefits of DSCM and highlights the need for further research into CPR algorithms that specifically target the effect of nonlinear phase noise (NLPN).
In a subcarrier multiplexing 125 Gbaud DP-PCS-64QAM system with a net bitrate of 800 Gbit/s, we numerically and experimentally study the performance of transmission-aware carrier phase estimation ...(CPE) for long-haul systems. The recently proposed transmission-aware dual-reference subcarrier CPE (DRS-CPE) is assessed against a more conventional per-subcarrier CPE approach and a transmission-agnostic joint CPE in 8- and 16-subcarrier transmission. At laser linewidths of <inline-formula><tex-math notation="LaTeX">\sim</tex-math></inline-formula>150 kHz, we achieve an experimental signal-to-noise ratio gain over a single-carrier of up to 0.5 dB after 1800 km transmission, enabled by the DRS-CPE.
Abstract Background Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive ...alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual “omics” signature that distinguishes subjects with varying cognitive profiles. Results We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. Conclusions These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.
Localized stress and cell death in chronic inflammatory diseases may release tissue-specific lipids into the circulation causing the blood plasma lipidome to reflect the type of inflammation. ...However, deep lipid profiles of major chronic inflammatory diseases have not been compared.
Plasma lipidomes of patients suffering from two etiologically distinct chronic inflammatory diseases, atherosclerosis-related vascular disease, including cardiovascular (CVD) and ischemic stroke (IS), and systemic lupus erythematosus (SLE), were screened by a top-down shotgun mass spectrometry-based analysis without liquid chromatographic separation and compared to each other and to age-matched controls. Lipid profiling of 596 lipids was performed on a cohort of 427 individuals. Machine learning classifiers based on the plasma lipidomes were used to distinguish the two chronic inflammatory diseases from each other and from the controls.
Analysis of the lipidomes enabled separation of the studied chronic inflammatory diseases from controls based on independent validation test set classification performance (CVD vs control - Sensitivity: 0.94, Specificity: 0.88; IS vs control - Sensitivity: 1.0, Specificity: 1.0; SLE vs control – Sensitivity: 1, Specificity: 0.93) and from each other (SLE vs CVD ‒ Sensitivity: 0.91, Specificity: 1; IS vs SLE - Sensitivity: 1, Specificity: 0.82). Preliminary linear discriminant analysis plots using all data clearly separated the clinical groups from each other and from the controls, and partially separated CVD severities, as classified into five clinical groups. Dysregulated lipids are partially but not fully counterbalanced by statin treatment.
Dysregulation of the plasma lipidome is characteristic of chronic inflammatory diseases. Lipid profiling accurately identifies the diseases and in the case of CVD also identifies sub-classes.
Full list of funding sources at the end of the manuscript.
Purpose. To report the long-term clinical outcomes after switching from intravitreal bevacizumab or ranibizumab to aflibercept therapy in eyes with AMD. Methods. Retrospective analysis of changes in ...BCVA, SD-OCT image, and frequency of injections after 1, 2, and 3 years of follow-up. Results. 164 eyes were analyzed, 101 eyes switched from bevacizumab (group 1) and 63 from ranibizumab (group 2). One year after the switch, there was an overall nonsignificant mean decrease of 2 ETDRS letters in BCVA. Three years after, there was an overall mean decrease of 7 ETDRS letters, which was statistically significant. A significant improvement in the mean CRT was found at 1, 2, and 3 years. There was a significant decrease in the mean number of injections per year (7.8 to 6.5, p<0.005) between the first and third year. Conclusion. Aflibercept can be useful in the management of refractory neovascular AMD, with a good morphological response. However, in the long-term, BCVA stabilization was not achieved.
Theoretical gains of digital multi-carrier systems are hindered by the use of sub-optimal conventional phase recovery, especially after fiber transmission. We experimentally validate an advanced, ...dispersion-aware algorithm that addresses this issue, achieving SNR gains up to ∼0.5 dB with 800G 125 Gbaud 16-carrier PCS-64QAM, transmitted over 1800 km.
We propose a novel Dual-Reference Subcarrier (DRS) algorithm for improved carrier-phase estimation in long-haul Multi-Subcarrier (MSC) systems. For a 64 Gbaud 64QAM MSC signal, the DRS algorithm is ...shown to enable penalty-free operation with symbol-rates per subcarrier as low as 2 Gbaud.
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