Hypotension with neurovascular changes and cognitive dysfunction: An epidemiological, pathobiological, and treatment review.

ABSTRACT: Hypotension is a leading cause of age-related cognitive impairment. The available literature evidences that vascular factors are associated with dementia and that hypotension alters cerebral perfusion flow and can aggravate the neurodegeneration of Alzheimer's disease (AD). Despite the discovery of biomarkers and the recent progress made in neurovascular biology, epidemiology, and brain imaging, some key issues remain largely unresolved: the potential mechanisms underlying the neural deterioration observed in AD, the effect of cerebrovascular alterations on cognitive deficits, and the positive effects of hypotension treatment on cognition. Therefore, further well-designed studies are needed to unravel the potential association between hypotension and cognitive dysfunction and reveal the potential benefits of hypotension treatment for AD patients. Here, we review the current epidemiological, pathobiological, and treatment-related literature on neurovascular changes and hypotension-related cognitive dysfunction and highlight the unsettled but imminent issues that warrant future research endeavors.

Brain white matter changes and their associations with non-motor dysfunction in orthostatic hypotension in α-synucleinopathy: A NODDI study.

BACKGROUND: The specific non-motor symptoms associated with α-synucleinopathies, including orthostatic hypotension (OH), cognitive impairment, and emotional abnormalities, have been a subject of ongoing controversy over the mechanisms underlying the development of a vicious cycle among them. The distinct structural alterations in white matter (WM) in patients with α-synucleinopathies experiencing OH, alongside their association with other non-motor symptoms, remain unexplored. This study employs axial diffusivity and density imaging (NODDI) to investigate WM damage specific to α-synucleinopathies with concurrent OH, delivering fresh evidence to supplement our understanding of the pathogenic mechanisms and pathological rationales behind the occurrence of a spectrum of non-motor functional impairments in α-synucleinopathies. METHODS: This study recruited 49 individuals diagnosed with α-synucleinopathies, stratified into an α-OH group (n = 24) and an α-NOH group (without OH, n = 25). Additionally, 17 healthy controls were included for supine and standing blood pressure data collection, as well as neuropsychological assessments. Magnetic resonance imaging (MRI) was utilized for the calculation of NODDI parameters, and tract-based spatial statistics (TBSS) were employed to explore differential clusters. The fibers covered by these clusters were defined as regions of interest (ROI) for the extraction of NODDI parameter values and the analysis of their correlation with neuropsychological scores. RESULTS: The TBSS analysis unveiled specific cerebral regions exhibiting disparities within the α-OH group as compared to both the α-NOH group and the healthy controls. These differences were evident in clusters that indicated a decrease in the acquisition of the neurite density index (NDI), a reduction in the orientation dispersion index (ODI), and an increase in the isotropic volume fraction (FISO) (p < 0.05). The extracted values from these ROIs demonstrated significant correlations with clinically assessed differences in supine and standing blood pressure, overall cognitive scores, and anxiety-depression ratings (p < 0.05). CONCLUSION: Patients with α-synucleinopathies experiencing OH exhibit distinctive patterns of microstructural damage in the WM as revealed by the NODDI model, and there is a correlation with the onset and progression of non-motor functional impairments.

Aberrant microstructural integrity of white matter in mild and severe orthostatic hypotension: A NODDI study.

OBJECTIVE: Scarce evidence is available to elucidate the association between the abnormal microstructure of white matter (WM) and cognitive performance in patients with orthostatic hypotension (OH). This study investigated the microstructural integrity of WM in patients with mild OH (MOH) and severe OH (SOH) and evaluated the association of abnormal WM microstructure with the broad cognitive domains and cognition-related plasma biomarkers. METHODS: Our study included 72 non-OH (NOH), 17 MOH, and 11 SOH participants. Across the groups, the WM integrity was analyzed by neurite orientation dispersion and density imaging (NODDI), and differences in WM microstructure were evaluated by nonparametric tests and post hoc models. The correlations between WM microstructure and broad cognitive domains and cognition-related plasma biomarkers were assessed by Spearman's correlation analysis. RESULTS: The abnormal WM microstructure was localized to the WM fiber bundles in MOH patients but distributed widely in SOH cohorts (p < 0.05). Further analysis showed that the neurite density index of the left cingulate gyrus was negatively associated with amyloid ß-40, glial fibrillary acidic protein, neurofilament light chain, phospho-tau181 (p < 0.05) but positively with global cognitive function (MOCA, MMSE, AER-III), memory, attention, language, language fluency, visuospatial function and amyloid ß-40 / amyloid ß-42 (p < 0.05). Additionally, other abnormal WM microstructures of OH were associated with broad cognitive domains and cognition-related plasma biomarkers to varying degrees. CONCLUSION: The findings evidence that abnormal WM microstructures may present themselves as early as in the MOH phase and that these structural abnormalities are associated with cognitive functions and cognition-related plasma biomarkers.

Synchronous monitoring of brain-heart electrophysiology using heart rate variability coupled with rapid quantitative electroencephalography in orthostatic hypotension patients with α-synucleinopathies: Rapid prediction of orthostatic hypotension and preliminary exploration of brain stimulation therapy.

BACKGROUND: In α-synucleinopathies, the dysfunction of the autonomic nervous system which typically manifests as orthostatic hypotension (OH) often leads to severe consequences and poses therapeutic challenges. This study aims to discover the brain-cardiac electrophysiological changes in OH patients with α-synucleinopathies using the rapid quantitative electroencephalography (qEEG) coupled with heart rate variability (HRV) technique to identify rapid, noninvasive biomarkers for early warning and diagnosis, as well as shed new light on complementary treatment approaches such as brain stimulation targets. METHODS: In this study, 26 subjects of α-synucleinopathies with OH (α-OH group), 21 subjects of α-synucleinopathies without OH (α-NOH group), and 34 healthy controls (control group) were included from September 2021 to August 2023 (NCT05527067). The heart rate-blood pressure variations in supine and standing positions were monitored, and synchronization parameters of seated resting-state HRV coupled with qEEG were collected. Time-domain and frequency-domain of HRV measures as well as peak frequency and power of the brainwaves were extracted. Differences between these three groups were compared, and correlations between brain-heart parameters were analyzed. RESULTS: The research results showed that the time-domain parameters such as MxDMn, pNN50, RMSSD, and SDSD of seated resting-state HRV exhibited a significant decrease only in the α-OH group compared to the healthy control group (p < 0.05), while there was no significant difference between the α-NOH group and the healthy control group. Several time-domain and frequency-domain parameters of seated resting-state HRV were found to be correlated with the blood pressure changes within the first 5 min of transitioning from supine to standing position (p < 0.05). Differences were observed in the power of beta1 waves (F4 and Fp2) and beta2 waves (Fp2 and F4) in the seated resting-state qEEG between the α-OH and α-NOH groups (p < 0.05). The peak frequency of theta waves in the Cz region also showed a difference (p < 0.05). The power of beta2 waves in the Fp2 and F4 brain regions correlated with frequency-domain parameters of HRV (p < 0.05). Additionally, abnormal electrical activity in the alpha, theta, and beta1 waves was associated with changes in heart rate and blood pressure within the first 5 min of transitioning from supine to standing position (p < 0.05). CONCLUSION: Rapid resting-state HRV with certain time-domain parameters below normal levels may serve as a predictive indicator for the occurrence of orthostatic hypotension (OH) in patients with α-synucleinopathies. Additionally, the deterioration of HRV parameters correlates with synchronous abnormal qEEG patterns, which can provide insights into the brain stimulation target areas for OH in α-synucleinopathy patients.

Efficacy analysis of three brain stimulation techniques for Alzheimer's disease: a meta-analysis of repeated transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation.

INTRODUCTION: This systematic review and meta-analysis study investigates the efficacy of repeated transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS) using neuropsychological assessments as a potential treatment option for Alzheimer's disease (AD). METHODS: PubMed, Embase, and the Cochrane Library were searched for studies on rTMS, tDCS, and DBS for the treatment of patients with AD between April 1970 and October 2022. The mini-Mental State Examination (MMSE) and AD Assessment Scale - Cognitive Subscale (ADAS-Cog) were adopted as the efficacy index. RESULTS: The analysis yielded 17 eligible studies. rTMS greatly improved the cognition of patients with AD (immediate post-treatment WMD of MMSE score: 2.06, p < 0.00001; short-term follow-up WMD of MMSE score: 2.12, p = 0.006; WMD of ADAS-Cog score in single-arm studies: -4.97, p = 0.001). DBS did not reverse the progression of cognitive decline (WMD of ADAS-Cog score in single-arm studies: 7.40, p < 0.00001). Furthermore, tDCS demonstrated no significant efficacy in improving cognition in random clinical trials or single-arm studies. CONCLUSION: rTMS is a promising non-medicinal alternative for cognitive improvement inpatients with AD.

Broadband photonic-assisted microwave receiver with high cross-channel interference suppression and image rejection.

A broadband photonic-assisted microwave receiver with high cross-channel interference suppression and image rejection is proposed and experimentally demonstrated. At the input of the microwave receiver, a microwave signal is injected into an optoelectronic oscillator (OEO), which functions as a local oscillator (LO) to generate a low-phase noise LO signal as well as a photonic-assisted mixer to down-convert the input microwave signal to the intermediate frequency (IF). A microwave photonic filter (MPF), realized by the joint operation of a phase modulator (PM) in the OEO and a Fabry-Perot laser diode (FPLD), is used as a narrowband filter to select the IF signal. Thanks to the wide bandwidth of the photonic-assisted mixer and the wide frequency tunable range of the OEO, the microwave receiver can support broadband operation. The high cross-channel interference suppression and image rejection are enabled by the narrowband MPF. The system is evaluated experimentally. A broadband operation from 11.27 to 20.85 GHz is demonstrated. For a multi-channel microwave signal with a channel spacing of 2 GHz, a cross-channel interference suppression ratio of 21.95 dB and an image rejection ratio of 21.51 dB are realized. The spurious-free dynamic range (SFDR) of the receiver is also measured to be 98.25 dB·Hz2/3. The performance of the microwave receiver for multi-channel communications is also experimentally evaluated.

Intensive blood pressure control for patients aged over 60: A meta-analysis of the SPRINT, STEP, and ACCORD BP randomized controlled trials.

OBJECTIVES: To evaluate the effects of intensive treatment to lower blood pressure (BP) on the risk of cardiovascular disease (CVD) among patients aged over 60 years. STUDY DESIGN: We extracted individual-level data of participants aged over 60 years from the SPRINT study and ACCORD study first, and then conducted a meta-analysis of major adverse cardiovascular events (MACEs) and other adverse events (hypotension and syncope) and renal outcomes across the SPRINT, STEP, ACCORD BP trials, which included 18,806 participants over 60 years of age. Participants were randomized to receive standard BP treatment or intensive BP treatment. MAIN OUTCOME MEASURES: Hazard ratios (HRs) were used to calculate summary statistics. RESULTS: In this meta-analysis, intensive treatment did not decrease either the all-cause mortality rate (HR: 0.98; 95 % confidence interval [CI]: 0.76-1.26; p = 0.87) or the cardiovascular mortality rate (HR: 0.77; 95 % CI: 0.54-1.08; p = 0.13). The incidence of MACEs (HR: 0.83; 95 % CI: 0.74-0.94; p = 0.003) and stroke (HR: 0.70; 95 % CI: 0.56-0.88; p = 0.002) was reduced, however. Intensive treatment had no effect on acute coronary syndrome (HR: 0.87; 95 % CI: 0.69-1.10; p = 0.24) or heart failure (HR: 0.70; 95 % CI: 0.40-1.22; p = 0.21). Intensive treatment increased the risk of hypotension (HR: 1.46; 95 % CI: 1.12-1.91; p = 0.006) and syncope (HR: 1.43; 95 % CI: 1.06-1.93; p = 0.02). Intensive treatment did not increase the risk of impaired kidney function among patients with chronic kidney disease (HR: 0.98; 95 % CI: 0.41-2.34; p = 0.96) or without chronic kidney disease (HR: 1.77; 95 % CI: 0.48-6.56; p = 0.40) at baseline. CONCLUSIONS: Intensive BP goals reduced the incidence of MACEs and increased the risk of other adverse events without significant changes in mortality or renal outcome.

Transcriptome analysis reveals potential marker genes for diagnosis of Alzheimer's disease and vascular dementia.

Alzheimer's disease (AD) and vascular dementia (VD) are the two most common forms of dementia, share similar symptoms, and are sometimes difficult to distinguish. To investigate the potential mechanisms by which they differ, we identified differentially expressed genes in blood and brain samples from patients with these diseases, and performed weighted gene co-expression network analysis and other bioinformatics analyses. Weighted gene co-expression network analysis resulted in mining of different modules based on differences in gene expression between these two diseases. Enrichment analysis and generation of a protein-protein interaction network were used to identify core pathways for each disease. Modules were significantly involved in cAMP and AMPK signaling pathway, which may be regulated cell death in AD and VD. Genes of cAMP and neurotrophin signaling pathways, including ATP1A3, PP2A, NCEH1, ITPR1, CAMKK2, and HDAC1, were identified as key markers. Using the least absolute shrinkage and selection operator method, a diagnostic model for AD and VD was generated and verified through analysis of gene expression in blood of patients. Furthermore, single sample gene set enrichment analysis was used to characterize immune cell infiltration into brain tissue. That results showed that infiltration of DCs and pDCs cells was increased, and infiltration of B cells and TFH cells was decreased in the brain tissues of patients with AD and VD. In summary, classification based on target genes showed good diagnostic efficiency, and filled the gap in the diagnostic field or optimizes the existing diagnostic model, which could be used to distinguish between AD and VD.

Multi-Scale Effects of Meteorological Conditions and Anthropogenic Emissions on PM2.5 Concentrations over Major Cities of the Yellow River Basin.

The mechanism behind PM2.5 pollution is complex, and its performance at multi-scales is still unclear. Based on PM2.5 monitoring data collected from 2015 to 2021, we used the GeoDetector model to assess the multi-scale effects of meteorological conditions and anthropogenic emissions, as well as their interactions with PM2.5 concentrations in major cities in the Yellow River Basin (YRB). Our study confirms that PM2.5 concentrations in the YRB from 2015 to 2021 show an inter-annual and inter-season decreasing trend and that PM2.5 concentrations varied more significantly in winter. The inter-month variation of PM2.5 concentrations shows a sinusoidal pattern from 2015 to 2021, with the highest concentrations in January and December and the lowest from June to August. The PM2.5 concentrations for major cities in the middle and downstream regions of the YRB are higher than in the upper areas, with high spatial distribution in the east and low spatial distribution in the west. Anthropogenic emissions and meteorological conditions have similar inter-annual effects, while air pressure and temperature are the two main drivers across the whole basin. At the sub-basin scale, meteorological conditions have stronger inter-annual effects on PM2.5 concentrations, of which temperature is the dominant impact factor. Wind speed has a significant effect on PM2.5 concentrations across the four seasons in the downstream region and has the strongest effect in winter. Primary PM2.5 and ammonia are the two main emission factors. Interactions between the factors significantly enhanced the PM2.5 concentrations. The interaction between ammonia and other emissions plays a dominant role at the whole and sub-basin scales in summer, while the interaction between meteorological factors plays a dominant role at the whole-basin scale in winter. Our study not only provides cases and references for the development of PM2.5 pollution prevention and control policies in YRB but can also shed light on similar regions in China as well as in other regions of the world.

Single-mode narrow-linewidth fiber ring laser with SBS-assisted parity-time symmetry for mode selection.

A single-longitudinal-mode narrow-linewidth fiber ring laser with stimulated Brillouin scattering (SBS) assisted parity-time (PT) symmetry for mode selection in a single fiber loop is proposed and experimentally demonstrated. When an optical pump is launched into the fiber loop along one direction, an SBS gain for the Stokes light along the opposite direction is produced. For two light waves at the Stokes frequency propagating along the two opposite directions, one will have a net gain and the other will have a net loss. By incorporating a fiber Bragg grating (FBG) with partial reflection in the loop, mutual coupling between the two counterpropagating Stokes light waves is achieved. The SBS gain can be controlled by tuning the angle between the polarization directions of the pump and the Stokes light waves through a polarization controller (PC). Once the gain and loss coefficients between the two counterpropagating light waves are controlled to be identical in magnitude, and that the gain coefficient is greater than the coupling coefficient caused by the FBG, PT symmetry breaking is achieved, making the mainmode to sidemode ratio highly enhanced, single mode lasing is thus achieved. The approach is evaluated experimentally. For a fiber ring laser with a cavity length of 8.02 km, single-mode lasing with a narrow 3-dB linewidth of 368 Hz and a sidemode suppression ratio of around 33 dB is demonstrated. The wavelength tunable range from 1550.02 to 1550.18 nm is also demonstrated.

Effects of anthropogenic precursor emissions and meteorological conditions on PM2.5 concentrations over the "2+26" cities of northern China.

Elucidating the characteristics and influencing mechanisms of PM2.5 concentrations is the premise and key to the precise prevention and control of air pollution. However, the temporal and spatial heterogeneity of PM2.5 concentrations and its driving mechanism are complex and need to be further analyzed. We analyzed the temporal and spatial variations of PM2.5 concentrations in the "2 + 26" cities from 2015 to 2021, and quantified the influence of meteorological factors and anthropogenic emissions and their interactions on PM2.5 concentrations based on geographic detector model. We find the inter-annual and inter-season PM2.5 concentrations show downward trend from 2015 to 2021, and the inter-month PM2.5 concentrations present a U-shaped distribution. The PM2.5 concentrations in the "2 + 26" cities manifest a spatial distribution pattern of high in the south and low in the north, and high in the middle and low in the surroundings. Meteorological conditions have stronger effects on PM2.5 concentrations than anthropogenic emissions, and planetary boundary layer height and temperature are the two main driving factors at the annual scale. On the seasonal scale, sunshine duration is the dominant factor of PM2.5 concentrations in summer and autumn, and planetary boundary layer height is the dominant factor of PM2.5 concentrations in winter. The effect of anthropogenic emissions on PM2.5 concentration is higher in winter and spring than in summer and autumn, and ammonia and ozone have stronger effects on PM2.5 concentrations than other anthropogenic emissions. Interactions between the factors significantly enhance the PM2.5 concentrations. The interactions between planetary boundary layer height and other impacting factors play dominant roles on PM2.5 concentrations at annual scale and in winter. Our results not only provide crucial information for further developing air quality policies of the "2 + 26" cities, but also bear out several important implications for clean air policies in China and other regions of the world.

Microwave frequency measurement using a silicon integrated microring resonator.

Photonics-assisted instantaneous frequency measurement of a microwave signal using a silicon integrated microring resonator (MRR) is proposed and experimentally demonstrated. The frequency of a microwave signal has a unique relationship with the power ratio between the two microwave signals at the outputs of two microwave photonic filters (MPF) with complementary frequency responses. The key device to implement the MPFs is a silicon integrated MMR, which is employed to convert a phase-modulated optical signal to an intensity-modulated optical signal by placing two optical carriers at the complementary slopes of the MRR. For a given frequency measurement range and resolution, an MRR is designed and fabricated, and its use for instantaneous microwave frequency (IMF) measurement is implemented. For the fabricated MRR, an IMF measurement range of 14-25 GHz with a measurement accuracy of ±0.2GHz is achieved.

Optoelectronic oscillator with improved sidemode suppression by joint use of spectral Vernier effect and parity-time symmetry.

An optoelectronic oscillator (OEO) with improved sideband suppression by joint use of the spectral Vernier effect and parity-time (PT) symmetry is proposed and experimentally demonstrated. The spectral Vernier effect is implemented using two mutually coupled loops with different loop lengths, to increase the effective free spectral range (FSR). To further increase the mode selection capability to ensure stable single-frequency oscillation with an increased sidemode suppression ratio (SMSR), PT symmetry is implemented, in which the two mutually coupled loops are controlled with balanced gain and loss. Thanks to the combined effects, stable single-mode oscillation with a significantly increased SMSR is achieved. The proposed OEO is studied theoretically and evaluated experimentally. The results show that for a generated microwave signal at 10 GHz, the SMSR is 67.68 dB, which is increased by 11.20 dB or 26.05 dB, when using only the spectral Vernier effect or only the PT symmetry. Thanks to the long length of the longer loop, good phase noise performance is still maintained. The measurement shows that a phase noise as low as -124.5 dBc/Hz at an offset frequency of 10 kHz is achieved.

Photonic generation of a microwave waveform with an ultra-long temporal duration using a frequency-shifting dispersive loop.

A photonic approach to generate a linearly chirped microwave waveform (LCMW) with an ultra-long temporal duration is proposed and experimentally demonstrated. The microwave waveform generation is achieved based on spectral-shaping and wavelength-to-time (SS-WTT) mapping by using a Mach-Zehnder interferometer (MZI) and a frequency-shifting dispersive loop (FSDL), respectively. To make the generated microwave waveform have an ultra-long temporal duration, the FSDL is operating to allow a spectrally shaped optical pulse to recirculate in a dispersive loop multiple times with a low propagating loss, to generate a microwave waveform with a temporal duration that is more than one order of magnitude longer than that of a microwave waveform generated using a dispersive element without recirculation. To generate a LCMW, the spectral shaper is configured to have a free spectral range (FSR) that is linearly increasing or decreasing with optical wavelength. The proposed approach is experimentally demonstrated. Two LCMWs, by allowing an optical pulse recirculating in the FSDL for three and seven round trips, tripled and septupled temporal durations of 64 and 182 ns are generated. The generation of two LCMWs with ultra-long temporal durations of 370 ns and 450 ns are also demonstrated.

Low jitter microwave pulse train generation based on an optoelectronic oscillator.

We demonstrate an approach to ultra-short pulse train generation with a low time jitter based on pulse compression of a frequency comb generated by a dual-loop optoelectronic oscillator (OEO). The proposed dual-loop OEO consists of two feedback loops, with one having a long loop length and the other a short loop length. In the long loop, a phase modulator (PM) cascaded with a Mach-Zehnder modulator (MZM) are employed, and in the short loop, only the MZM is included. Due to the Vernier effect, the use of the dual-loop structure can facilitate mode selection to generate a single-frequency microwave carrier with multiple optical sidebands corresponding to an optical comb. By adjusting the phase relationship between the optical sidebands using a dispersion compensating fiber (DCF), a stable optical pulse train is generated. Thanks to the low phase noise nature of an OEO, the generated pulse train has a low time jitter. The proposed approach is evaluated experimentally. A pulse train with a repetition frequency of 2.023 GHz and a pulse width of 40 ps is generated. The single-sideband (SSB) phase noise of the carrier frequency generated by the OEO is measured to be -118 dBc/Hz at a 10-kHz offset frequency, corresponding to a time jitter of the pulse train of 391.2 fs. The phase noise can be further reduced if an active cavity stabilization mechanism is adopted, enabling further reduction in the time jitter to the order of tens of femtoseconds.

Polarimetric parity-time symmetry in a photonic system.

Parity-time (PT) symmetry has attracted intensive research interest in recent years. PT symmetry is conventionally implemented between two spatially distributed subspaces with identical localized eigenfrequencies and complementary gain and loss coefficients. The implementation is complicated. In this paper, we propose and demonstrate that PT symmetry can be implemented between two subspaces in a single spatial unit based on optical polarimetric diversity. By controlling the polarization states of light in the single spatial unit, the localized eigenfrequencies, gain, loss, and coupling coefficients of two polarimetric loops can be tuned, leading to PT symmetry breaking. As a demonstration, a fiber ring laser based on this concept supporting stable and single-mode lasing without using an ultranarrow bandpass filter is implemented.

Parity-time symmetry in wavelength space within a single spatial resonator.

We show a parity-time (PT) symmetric microwave photonic system in the optical wavelength space within a single spatial resonator, in which the gain and loss modes can perfectly overlay spatially but are distinguishable in the designated parameter space. To prove the concept, a PT-symmetric optoelectronic oscillator (OEO) in the optical wavelength space is implemented. The OEO has a single-loop architecture, with the microwave gain and loss modes carried by two optical wavelengths to form two mutually coupled wavelength-space resonators. The operation of PT symmetry in the OEO is verified by the generation of a 10-GHz microwave signal with a low phase noise of -129.3 dBc/Hz at 10-kHz offset frequency and small sidemodes of less than -66.22 dBc/Hz. Compared with a conventional spatial PT-symmetric system, a PT-symmetric system in the wavelength space features a much simpler configuration, better stability and greater resilience to environmental interferences.

Optical dynamic memory based on an integrated active ring resonator.

All-optical computing has been considered a solution for future computers to overcome the speed bottleneck encountered by the current electronic computers. High-speed optical memory is one of the key building blocks in realizing all-optical computing. In this Letter, we demonstrate an optical dynamic memory based on an amplified high Q-factor ring resonator that has the capability to achieve an infinite memory time. The optical memory uses an external pulse train to refresh the resonator, an operation in analogy to an electronic dynamic random-access memory widely used in modern computers, but at a speed that can be orders of magnitude faster. In our demonstration, a writing speed of 2.5 GHz is achieved with instant reading capability. The maximum writing speed can be as fast as 27.3 GHz if a shorter pulse is used.

Parity-time-symmetric optoelectronic oscillator.

An optoelectronic oscillator (OEO) is a hybrid microwave and photonic system incorporating an amplified positive feedback loop to enable microwave oscillation to generate a high-frequency and low-phase noise microwave signal. The low phase noise is ensured by the high Q factor of the feedback loop enabled by the use of a long and low-loss optical fiber. However, an OEO with a long fiber loop would have a small free spectral range, leading to a large number of closely spaced oscillation modes. To ensure single-mode oscillation, an ultranarrowband optical filter must be used, but such an optical filter is hard to implement and the stability is poor. Here, we use a novel concept to achieve single-mode oscillation without using an ultranarrowband optical filter. The single-mode operation is achieved based on parity-time (PT) symmetry by using two identical feedback loops, with one having a gain and the other having a loss of the same magnitude. The operation is analyzed theoretically and verified by an experiment. Stable single-mode oscillation at an ultralow phase noise is achieved without the use of an ultranarrowband optical filter. The use of PT symmetry in an OEO overcomes the long-existing mode-selection challenge that would greatly simplify the implementation of OEOs for ultralow-phase noise microwave generation.

Genotype-phenotype correlation and frequency of distribution in a cohort of Chinese Charcot-Marie-Tooth patients associated with GDAP1 mutations.

Mutations in ganglioside-induced differentiation-associated-protein 1 (GDAP1) have been associated with both subtypes of Charcot-Marie-Tooth (CMT) disease, autosomal recessive (CMT4A and AR-CMT2K) and autosomal dominant (AD-CMT2K). Over 80 different mutations have been identified so far. With the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 306 unrelated Chinese CMT patients and identified 8 variants in the GDAP1 gene in 4 families, 5 of which were novel (R41H, N201Kfs*5, Q38X, V215I and Q38R). Application of Bioinformatics tool and classification according to the American College of Medical Genetics (ACMG) predicted them of being likely pathogenic with the exception of one variant of uncertain significance (VUS). In addition, we detected the presence of a single heterozygous variant of uncertain significance H256R in one additional family from the CMT cohorts. We found a GDAP1 prevalence rate of 1.63% (5/306). Three families (families 1, 2 and 3) were found to have an autosomal recessive (AR) pattern of inheritance while family 4 displayed an autosomal dominant (AD) mode of inheritance. Electro-physiologic studies revealed an axonal type of neuropathy (AR-CMT2K and AD-CMT2K) in all affected individuals. Clinical characteristics and findings in our study demonstrated that the recessive form presented earlier in life and exhibited severe symptoms and rapid evolution compared to the dominant form. We observed a marked intra-familial variability within the AD family in terms of age at disease onset, symptom severity and clinical progression. Our study expands the mutational spectrum of GDAP1-related CMT disease with the identification of new and unreported GDAP1 variants and demonstrates the predominance of the axonal form of neuropathy in CMT disease associated with GDAP1. We highlight the clinical characteristics associated with these genotypes and describe the relative frequency of GDAP1 variants amongst the Chinese population.