Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation.

We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from ∼7.1 to ∼1.7 nm, corresponding to a pulse-width-tuning range from ∼350 fs to ∼1.56 ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of ∼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.

GHz-rate 57-fs acousto-optic mode-locking fiber laser based on cascaded all-fiber pulse compression.

We demonstrate a compact ultrafast fiber laser system that can deliver 1.87 GHz pulse train at 1550 nm with a pulse energy of 52 pJ and an ultrashort pulse duration of 57 fs. While an acousto-optic mode-locking fiber laser was used as the seed light source at GHz rate, a stage of Er-doped fiber amplifier boosted the laser power to ∼320 mW, giving a pulse energy of ∼170 pJ. Then, a pulse compression setup was constructed, providing a high compression ratio of ∼10 with a total efficiency of ∼32%. In the cascaded compression configuration, multiple fiber samples with alternately normal and anomalous dispersion were fused together, providing efficient nonlinear spectral broadening while suppressing excessive pulse broadening over propagation. This GHz-rate ultrafast fiber laser, with compact configuration, broad optical spectrum, and high time-resolving ability could be used as the seed light source for constructing high-rate, high-power ultrafast laser systems and may find a few applications in optical measurements and microwave photonics.

The Osmolality and Hemolysis of High-Concentration Monoclonal Antibody Formulations.

PURPOSES: Highly concentrated monoclonal antibody (mAb) formulations for subcutaneous administration are becoming increasingly preferred within the biopharmaceutical industry for ease of use and improved patient compliance. A common phenomenon observed in the industry is that osmolality detected via freezing-point depression (FPD) in high-concentration mAb formulations is much higher than the theoretical concentrations, yet the occurrence of this phenomenon and its possible safety issues have been rarely reported. METHODS: The current study summarized theoretical osmolality of U.S. Food and Drug Administration approved high-concentration mAb formulations and evaluated effects of high osmolality on safety using hemolysis experiments for the first time. Two mAbs formulated at 150 mg/mL were used as models and configured into two isotonic solutions: a, a theoretically calculated molarity in the isotonic range (H) and b, an osmolality value measured via the FPD in the isotonic range (I). The H and I formulations of each mAb were individually subjected to hemolysis experiments, and the hemolysis rates of the two formulations of the same mAb were compared. Besides, the effect of mAb concentration on osmolality detected by FPD was explored as well. RESULTS: The results indicated that the hemolysis rates were similar between the H and I formulations of mAbs at the same sample addition volume, and the osmolality values increased approximately linearly with the increase in mAb concentration. CONCLUSIONS: High osmolality for high-concentration mAb formulations would not affect product safety and the excipients could be added at relatively high levels to maintain product stability, especially for labile products.

Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho-1/Gpx4 pathway to prevent α-synuclein-induced ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α-synuclein (α-syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α-syn and ferroptosis in PD. Here, we used α-syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α-syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α-syn PFF-induced intracellular α-syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α-syn-induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.

Risk Factors and Clinical Characteristics of First-ever Ischemic Stroke Caused by ICAS with Leukoaraiosis.

Background: Previous studies have mostly investigated the risk factors affecting the occurrence of leukoaraiosis and the risk factors affecting the severity of leukoaraiosis in patients with ischemic stroke, but there are relatively few studies on the risk factors and clinical characteristics affecting the severity of leukoaraiosis in the population with the most common type of first-episode ischemic stroke caused by intracranial atherosclerotic stenosis in China. Methods: We retrospectively studied patients with first-ever ischemic stroke due to intracranial atherosclerotic stenosis. All patients underwent diffusion weight magnetic resonance imaging and adjunctive examinations such as magnetic resonance angiography and/or computed tomography angiography and/or digital subtraction angiography. The characteristics and clinical data were also statistically analyzed. Results: Of the 504 patients enrolled, 176 (34.92%), 202 (40.08%), and 126 (25.00%) patients were in the mild, moderate, and severe groups, respectively, and the patients were older in the severe group compared with the moderate and mild groups (p < 0.05). Hypertension was more severe in the severe group compared with the severe and mild groups (p < 0.05). The time to hospital admission was shorter in the severe group compared with the moderate and mild groups (p < 0.05). The admission National Institutes of Health stroke scale was higher in the severe group than in the moderate and mild groups (p < 0.05). homocysteine, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio, and ultrasensitive C-reactive protein to albumin ratio levels were significantly different between the three groups (p < 0.05). There was no significant correlation between the distribution of infarct foci in the anterior and posterior circulation in the three groups (p > 0.05). Conclusion: Age and homocysteine were independent risk factors for leukoaraiosis severity in patients with acute ischemic stroke, and all were positively associated with leukoaraiosis severity. Hypertension, glucose, glycohemoglobin A1c, neutrophil-lymphocyte ratio and ultrasensitive C-reactive protein to albumin ratio levels were highly significant in evaluating the prognosis of patients.

Experimental studies on the core-structure dependence of backward Brillouin gain in solid-core photonic crystal fibers.

Stimulated Brillouin scattering (SBS) in solid-core photonic crystal fibers (PCFs) differs significantly from that in standard optical fibers due to the tight confinement of both optical and acoustic fields in their µm-sized fiber cores, as resultantly evident in their Brillouin gain spectra. Despite many theoretical studies based on either simplified models or numerical simulations, the structural dependency of Brillouin gain spectra in small-core PCFs has not been characterized comprehensively using PCFs with elaborated parameter controls. In this work we report a comprehensive characterization on the core-structure dependences of backward SBS effects in solid-core PCFs that are drawn with systematically varied core-diameter, revealing several key trends of the fiber Brillouin spectrum in terms of its gain magnitude, Brillouin shift and multi-peak structure, which have not been reported in detail previously. Our work provides some practical guidance on PCF design for potential applications like Brillouin fiber lasers and Brillouin fiber sensing.

Highly stable, flexible delivery of microjoule-level ultrafast pulses in vacuumized anti-resonant hollow-core fibers for active synchronization.

We demonstrate the stable and flexible light delivery of multi-microjoule, sub-200-fs pulses over a ∼10-m-long vacuumized anti-resonant hollow-core fiber (AR-HCF), which was successfully used for high-performance pulse synchronization. Compared with the pulse train launched into the AR-HCF, the transmitted pulse train out of the fiber exhibits excellent stabilities in pulse power and spectrum, with pointing stability largely improved. The walk-off between the fiber-delivery and the other free-space-propagation pulse trains, in an open loop, was measured to be <6 fs root mean square (rms) over 90 minutes, corresponding to a relative optical-path variation of <2 × 10-7. This walk-off can be further suppressed to ∼2 fs rms simply by using an active control loop, highlighting the great application potentials of this AR-HCF setup in large-scale laser and accelerator facilities.

Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of α-synuclein (α-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. α-Syn is a crucial marker of PD, and its accumulation leads to microglia M1-like phenotype polarization, activation of NLRP3 inflammasomes, and impaired autophagy and phagocytosis in microglia. Autophagy of microglia is related to degradation of α-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released α-syn or fragments from apoptotic neurons maintain homeostasis in the brain. A variety of PD-related genes such as LRRK2, GBA and DJ-1 also contribute to this stability process. OBJECTIVES: Further studies are needed to determine how α-syn works in microglia. METHODS: A keyword-based search was performed using the PubMed database for published articles. CONCLUSION: In this review, we discuss the interaction between microglia and α-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in α-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.

Measurements of microjoule-level, few-femtosecond ultraviolet dispersive-wave pulses generated in gas-filled hollow capillary fibers.

To the best of our knowledge, we demonstrate the first time-domain measurement of µJ-level, few-fs ultraviolet dispersive-wave (DW) pulses generated in gas-filled hollow capillary fibers (HCFs) in an atmosphere environment using several chirped mirrors. The pulse temporal profiles, measured using a self-diffraction frequency-resolved optical gating setup, exhibit full width at half maximum pulse widths of 9.6 fs at 384 nm and 9.4 fs at 430 nm, close to the Fourier-transform limits. Moreover, theoretical and experimental studies reveal the strong influences of driving pulse energy and HCF length on temporal width and shape of the measured DW pulses. The ultraviolet pulses obtained in an atmosphere environment with µJ-level pulse energy, few-fs pulse width, and broadband wavelength tunability are ready to be used in many applications.

Freeze-Dried Biopharmaceutical Formulations are Surprisingly Less Stable than Liquid Formulations during Dropping.

PURPOSES: This article describes an interesting phenomenon in which optimized freeze-dried (FD) biopharmaceutical formulations are generally more prone to degradation than their liquid counterparts during dropping and proposes an underlying cause for this surprising phenomenon. METHODS: Two monoclonal antibodies (mAbs) and a fusion protein (FP) were used as model biopharmaceuticals. The stability after dropping stress was determined by ultraviolet-visible (UV-Vis), size exclusion high-performance liquid chromatography (SE-HPLC), micro-flow imaging (MFI), and dynamic light scattering (DLS). RESULTS: Contrary to what we would normally assume, the FD formulations of the three biopharmaceuticals studied here generally showed much higher amounts of protein sub-visible particles (SbVPs) than liquid formulations after applying the same dropping stress as determined by MFI and DLS. Traditional techniques, such as UV-Vis and SE-HPLC, could hardly detect such degradation. CONCLUSIONS: We propose that the higher temperature caused by dropping for the FD powders than the liquid formulations was probably one of the root causes for the higher amount of particles formed for the FD powders. We also recommend that dropping stress should be included for early-stage screening and choosing liquid versus FD biopharmaceutical formulations.

Feature selection may improve deep neural networks for the bioinformatics problems.

MOTIVATION: Deep neural network (DNN) algorithms were utilized in predicting various biomedical phenotypes recently, and demonstrated very good prediction performances without selecting features. This study proposed a hypothesis that the DNN models may be further improved by feature selection algorithms. RESULTS: A comprehensive comparative study was carried out by evaluating 11 feature selection algorithms on three conventional DNN algorithms, i.e. convolution neural network (CNN), deep belief network (DBN) and recurrent neural network (RNN), and three recent DNNs, i.e. MobilenetV2, ShufflenetV2 and Squeezenet. Five binary classification methylomic datasets were chosen to calculate the prediction performances of CNN/DBN/RNN models using feature selected by the 11 feature selection algorithms. Seventeen binary classification transcriptome and two multi-class transcriptome datasets were also utilized to evaluate how the hypothesis may generalize to different data types. The experimental data supported our hypothesis that feature selection algorithms may improve DNN models, and the DBN models using features selected by SVM-RFE usually achieved the best prediction accuracies on the five methylomic datasets. AVAILABILITY AND IMPLEMENTATION: All the algorithms were implemented and tested under the programming environment Python version 3.6.6. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Photoionization-assisted, high-efficiency emission of a dispersive wave in gas-filled hollow-core photonic crystal fibers.

We demonstrate that the phase-matched dispersive wave (DW) emission within the resonance band of a 25-cm-long gas-filled hollow-core photonic crystal fiber (HC-PCF) can be strongly enhanced by the photoionization effect of the pump pulse. In the experiments, we observe that as the pulse energy increases, the pump pulse gradually shifts to shorter wavelengths due to soliton-plasma interactions. When the central wavelength of the blueshifting soliton is close to the resonance band of the HC-PCF, high-efficiency energy transfer from the pump light to the DW in the visible region can be obtained. During this DW emission process, we observe that the spectral center of the DW gradually shifts to longer wavelengths leading to a slightly increased DW bandwidth, which can be well explained as the consequence of phase-matched coupling between the pump pulse and the DW. In particular, at an input pulse energy of 6 µJ, the spectral ratio of the DW at the fiber output is measured to be as high as ∼53%, corresponding to an overall conversion efficiency of ∼19%. These experimental results, well accompanied by theoretical simulations and analysis, offer a practical and effective method of generating high-efficiency tunable visible light sources and provide a few useful insights into the fields of soliton-plasma interaction and resonance-induced DW emission.

Pulse-repetition-rate tuning of a harmonically mode-locked fiber laser using a tapered photonic crystal fiber.

Strong enhancement of optoacoustic interactions in the micrometer-sized core of a photonic crystal fiber (PCF) enables stable, harmonic mode locking of a soliton fiber laser at GHz frequencies. Here we report that by tapering the PCF during the draw, the optoacoustic gain bandwidth can be broadened to ∼47 MHz, more than 3 times wider than in the untapered fiber. This made possible broad pulse-repetition-rate tuning over 66 MHz (from 2.042 to 2.108 GHz) of an optoacoustically mode-locked soliton fiber laser. Within this tuning range, the harmonically mode-locked pulse trains at the laser output were observed to be quite robust, with better than 40 dB supermode suppression ratio, sub-ps pulse timing jitter, and <0.2%relative intensity noise. This gigahertz-rate, near-infrared soliton fiber laser has remarkable pulse-rate tunability and low noise level, and has important potential applications in frequency metrology, high-speed optical sampling, and fiber telecommunications.

Supercontinuum generation in ZBLAN glass photonic crystal fiber with six nanobore cores.

Photonic crystal fibers (PCFs) made from ZBLAN glass are of great interest for generating broadband supercontinua extending into the ultraviolet and mid-infrared regions. Precise sub-micrometer structuring makes it possible to adjust the modal dispersion over a wide range, making the generation of new frequencies more efficient. Here we report a novel ZBLAN PCF with six cores, each containing a central nanobore of a diameter ∼330 nm. Each nanobore core supports several guided modes, and the presence of the nanobore significantly modifies the dispersion, strongly influencing the dynamics and the extent of supercontinuum generation. Spectral broadening is observed when a single core is pumped in the fundamental and first higher order core modes with 200 fs long pulses at a wavelength of 1042 nm. Frequency-resolved optical gating is used to characterize the output pulses when pumping in the lowest order mode. The results are verified by numerical simulations.

Wideband-tunable soliton fiber laser mode-locked at 1.88 GHz by optoacoustic interactions in solid-core PCF.

We report a wavelength-tunable soliton fiber laser stably mode-locked at 1.88 GHz (the 389th harmonic of the cavity round-trip frequency) by a light-driven acoustic resonance in the core of a photonic crystal fiber. Stable high-harmonic mode-locking could be maintained when the lasing wavelength was continuously tuned from 1532 to 1566 nm by means of an optical filter placed inside the laser cavity. We report on the experimental performance of the laser, including its power scalability, super-mode noise suppression ratio, long-term repetition rate stability, short-term pulse amplitude noise and timing jitter, optical comb structure and pulse-to-pulse phase fluctuations.

Assessing tobacco-related ischemic stroke in Pakistan (1990-2019): Insights from the Global Burden of Disease Study.

INTRODUCTION: This study analyzes the impact of active smoking and secondhand smoke on the ischemic stroke burden of Pakistan, 1990-2019. METHODS: We used data from the Global Burden of Disease (GBD) database to conduct a comprehensive evaluation of ischemic stroke-related indicators in Pakistan, including the number of deaths, mortality rates, disability-adjusted life years (DALYs), DALY rates, and the estimated annual percentage change (EAPC). Joinpoint analysis was applied to assess sex-specific temporal trends in the burden of active smoking and secondhand smoke in Pakistan and regions of Pakistan. These assessments incorporated the Socio-Demographic Index (SDI) and we have made comparative analyses of epidemiological differences between active smoking and secondhand smoke exposure. RESULTS: The burden of ischemic stroke related to tobacco use is presented in terms of the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) per 100000 population. The results (ASMR/ASDR) for Pakistan were 6.04/130.81, in the middle SDI region 7.69/176.54, and low-middle SDI region 5.64/124.22. Pakistan's ASMR is higher than the global average of 5.85, while ASDR is lower than the global average of 140.23. From 1990 to 2019, a downward trend in both ASMR and ASDR was observed, indicating progress in controlling tobacco-related stroke burdens. Individuals aged ≥70 years experienced the highest rates of stroke (ASMR: 66.31; ASDR: 1091.20). Gender disparities were evident: men were more affected by active smoking (ASMR: 3.08; ASDR: 78.47) than women (ASMR: 0.79; ASDR: 20.76), while women faced a higher burden from secondhand smoke (ASMR: 0.66; ASDR: 16.33) compared to men (ASMR: 0.79; ASDR: 9.93). Regional differences within Pakistan show fluctuating death and DALY rates. Notably, an increasing trend in female ASDR due to secondhand smoke in the Khyber Pakhtunkhwa Region (annual percentage change, APC=0.17 from 2010 to 2019) calls for focused health interventions. CONCLUSIONS: The study finds ASMR for tobacco-related ischemic stroke in Pakistan exceeds global averages, with significant gender and age disparities in exposure to smoke, highlighting the need for targeted health interventions.

Heterogeneous Prototype Learning From Contaminated Faces Across Domains via Disentangling Latent Factors.

This article studies an emerging practical problem called heterogeneous prototype learning (HPL). Unlike the conventional heterogeneous face synthesis (HFS) problem that focuses on precisely translating a face image from a source domain to another target one without removing facial variations, HPL aims at learning the variation-free prototype of an image in the target domain while preserving the identity characteristics. HPL is a compounded problem involving two cross-coupled subproblems, that is, domain transfer and prototype learning (PL), thus making most of the existing HFS methods that simply transfer the domain style of images unsuitable for HPL. To tackle HPL, we advocate disentangling the prototype and domain factors in their respective latent feature spaces and then replacing the source domain with the target one for generating a new heterogeneous prototype. In doing so, the two subproblems in HPL can be solved jointly in a unified manner. Based on this, we propose a disentangled HPL framework, dubbed DisHPL, which is composed of one encoder-decoder generator and two discriminators. The generator and discriminators play adversarial games such that the generator embeds contaminated images into a prototype feature space only capturing identity information and a domain-specific feature space, while generating realistic-looking heterogeneous prototypes. Experiments on various heterogeneous datasets with diverse variations validate the superiority of DisHPL.

Inhibition of GluN2D-Containing NMDA Receptors Protects Dopaminergic Neurons against 6-OHDA-Induced Neurotoxicity via Activating ERK/NRF2/HO-1 Signaling.

Abnormal glutamate signaling is implicated in the heightened vulnerability of dopaminergic neurons in Parkinson's disease (PD). NMDA receptors are ion-gated glutamate receptors with high calcium permeability, and their GluN2D subunits are prominently distributed in the basal ganglia and brainstem nuclei. Previous studies have reported that dopamine depletion led to the dysfunctions of GluN2D-containing NMDA receptors in PD animal models. However, it remains unknown whether selective modulation of GluN2D could protect dopaminergic neurons against neurotoxicity in PD. In this study, we found that allosteric activation of GluN2D-containing NMDA receptors decreased the cell viability of MES23.5 dopaminergic cells and the GluN2D inhibitor, QNZ46, showed antioxidant effects and significantly relieved apoptosis in 6-OHDA-treated cells. Meanwhile, we demonstrated that QNZ46 might act via activation of the ERK/NRF2/HO-1 pathway. We also verified that QNZ46 could rescue abnormal behaviors and attenuate dopaminergic cell loss in a 6-OHDA-lesioned rat model of PD. Although the precise mechanisms underlying the efficacy of QNZ46 in vivo remain elusive, the inhibition of the GluN2D subunit should be a considerable way to treat PD. More GluN2D-selective drugs, which present minimal side effects and broad therapeutic windows, need to be developed for PD treatment in future studies.

Frequency stabilized coherent Brillouin random fiber laser: theory and experiments.

A coherent random fiber laser based on stimulated Brillouin scattering as gain and Rayleigh scattering as distributed feedback mirror was constructed. Its frequency is stabilized by a high finesse narrow-band Fabry-Perot interferometer (FPI) to select lasing frequency within the gain bandwidth. The light confinement within single-mode fiber enhances largely the random lasing directionality, which enables a high-quality coherent random lasing in the weak scattering region by using a milliwatt continuous-wave pump source. The FPI in the laser configuration acts as a frequency selection on the Rayleigh feedback light, and thus the random lasing frequency was locked at one of its transmission peaks giving a relative frequency fluctuation of ~2.5 × 10(-11) at 100 s. The measured frequency jitter is within ~~ ± 20 kHz over 3 hours, 3 dB linewidth is ~50 Hz and frequency noise is ~20 mHz/Hz(1/2) at 10 kHz.