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Concomitant malignant gastric outlet obstruction and biliary obstruction may occur in patients with advanced cancers affecting these anatomical regions. This scenario presents a unique challenge to the endoscopist in selecting an optimal management approach. We sought to determine the efficacy and safety of endoscopic techniques for treating simultaneous gastric outlet and biliary obstruction (GOBO) with endoscopic ultrasound (EUS) guidance for biliary drainage. An extensive literature search for peer-reviewed published cases yielded 6 unique case series that either focused on or included the use of EUS-guided biliary drainage (EUS-BD) with simultaneous gastroduodenal stenting. In our composite analysis, a total of 51 patients underwent simultaneous biliary drainage through EUS, with an overall reported technical success rate of 100% for both duodenal stenting and biliary drainage. EUS-guided choledochoduodenostomy or EUS-guided hepaticogastrostomy was employed as the initial technique. In 34 cases in which clinical success was ascribed, 100% derived clinical benefit. The common adverse effects of double stenting included cholangitis, stent migration, bleeding, food impaction, and pancreatitis. We conclude that simultaneous double stenting with EUS-BD and gastroduodenal stenting for GOBO is associated with high success rates. It is a feasible and practical alternative to percutaneous biliary drainage or surgery for palliation in patients with associated advanced malignancies.

A novel approach to realize broadband microwave spectrum sensing based on photonic RF channelization and compressive sampling (CS) is proposed. The photonic RF channelization system is used to slice the input broadband signal into multiple sub-channel signals with narrow bandwidth in parallel and thus the rate of pseudo-random binary sequence (PRBS) and the bandwidth of the MZM for CS can be largely decreased. It is shown that a spectrally sparse signal within a wide bandwidth can be captured with a sampling rate far lower than the Nyquist rate thanks to both photonic RF channelization and CS. In addition, the influence of the non-ideal filtering of the photonic channelizer is evaluated and a novel approach based on measuring twice is proposed to overcome the problem of frequency aliasing induced by the non-ideal filtering. It is demonstrated that a system with 20 Gbit/s PRBS and 2.5 GS/s digitizer can be used to capture a signal with multiple tones within a 40 GHz bandwidth, which means a sampling rate 32 times lower than the Nyquist rate.

We propose and experimentally demonstrate a novel and simple approach to identifying both the direction and value of Doppler frequency shift (DFS) in this paper. A pair of phase modulators, as well as a dispersion medium in between them, are employed in the approach. The different dispersion-induced phase shifts of the upper and lower sidebands after passing the dispersion medium can be used to determine the direction of DFS. The value of DFS is characterized by measuring the frequency of the output signal from a low-speed photodetector. Experimental results verify the feasibility of the approach. The major advantages of the approach lie in that it can measure both the DFS direction and value while avoids the use of complicated modulators and additional reference signal, which greatly simplifies the system's architecture.

This paper proposes a novel linear precoder design based on the singular value decomposition (SVD) for multi-input multi-output visible light communications (MIMO VLC). We provide an analytical expression on power allocation subject to the function of maximizing the lower bound of capacity according to the optical wireless communication channel model. The expression is rather different from the radio frequency (RF) communications due to the non-negativity of the transmitted signals in VLC. Furthermore, we design an adaptive bit loading scheme for sub-streams with consideration of the tremendous gain difference among subchannels. Performances of the proposed adaptive power and bits allocation strategy are evaluated in two traditional MIMO VLC scenarios, i.e., a practical 2×2 indoor scenario and a classical 4×4 system that is generated according to the MIMO model. In simulations, the techniques of unipolar M-level pulse amplitude modulation (M-PAM) and spatial-multiplexing (SMP) are employed, and the performance comparison with other SVD-based linear precoders is also given. Simulation results show that the proposed approach can effectively improve the spectral efficiency and guarantee the bit error rate (BER) performance under the same constraints of aggregate optical power budget and non-negativity included by the intensity modulation. It indicates that the strategy of uneven bits and power allocation with full consideration of the ill-conditioned characteristics of subchannels performs better than that based on equal bits transmission in VLC systems.

The structure and electrical characteristics of a dielectric resonator (abbreviated as DR hereafter) loaded plasmonic waveguide with controllable bandwidth are investigated in the present research. By loading the high permittivity dielectric medium on a spoof surface plasmonic waveguide, the working bandwidth of the filtering structure can be regulated flexibly due to the resonant effect of the loaded cylindrical DR. The DR is home-made and possesses the permittivity of 25.66, tanδ of 5.3 × 10-5 and stable temperature coefficient of -6.3 ppm/°C in microwave region. After the DR is loaded, the filtering structure can form the transmission zero on the edge of the pass band, regulating the bandwidth as well as increasing the out-of-band rejection. By controlling the height between the loaded DR and the substrate, or adjusting the inter-distance between the DRs, the relative bandwidth of the filtering structure can be effectively tailored.

The scattered Optical Network Units (ONUs) in an optical access network have different propagation delays. In an Ethernet passive optical network (EPON) adopting the traditional Interleaved Polling with Adaptive Cycle Time (IPACT) scheme, such ONU propagation delay difference will waste network resources and will degrade both network delay performance and network energy efficiency in delivering low-latency services. In this article, to deal with the heterogeneous ONU propagation delays problem, two solutions are proposed and investigated. The first solution, namely the Upstream Postponing with ONU Dozing (UP-OD) scheme, is to properly postpone the upstream transmissions of those ONUs having relatively short propagation delays to improve channel utilization efficiency, and ONU doze mode is incorporated to enhance network energy efficiency. The second solution, namely the Identical Fiber Length with ONU Sleeping (IFL-OS) scheme, is to adopt an identical distribution fiber length for ONUs to enhance channel utilization, and ONU sleep mode is incorporated for energy consumption reduction. Simulation results show that both the UP-OD scheme and the IFL-OS scheme reduce network delay and improve network energy efficiency in delivering low-latency (

The major limitation of the photonic digitization schemes based on the phase-shifting of modulation transfer function lies in its relatively low bit resolution, which is log2(2N ), where N is the number of optical channels or modulators. In this paper, we propose a novel photonic digitization scheme based on hierarchical quantization, which could greatly improve the system resolution with a relatively simple configuration. It is shown that 6N quantization levels, can be realized by using only three Mach-Zehnder modulators (MZMs) and a hierarchical quantization module (HQM) in the proposed scheme. By adjusting the fine quantization module inside HQM, the system resolution can be enhanced greatly. A proof-of-concept experiment is implemented, which fully verifies the correctness of the approach. Since simpler configuration and higher resolution are achieved, the proposed scheme provides a promising solution for high-performance photonic analog-to-digital conversion.

ABSTRACT Pseudomonas aeruginosa CtpA is a carboxyl-terminal processing protease that partners with the outer membrane lipoprotein LbcA to degrade at least five cell wall-associated proteins, four of which are cell wall hydrolases. This activity plays an important role in supporting P. aeruginosa virulence in a mouse model of acute pneumonia. However, almost nothing is known about the molecular mechanisms underlying CtpA and LbcA function. Here, we used structural analysis to show that CtpA alone assembles into an inactive hexamer comprising a trimer of dimers, which limits its substrate access and prevents nonspecific degradation. The adaptor protein LbcA is a right-handed open spiral with 11 tetratricopeptide repeats, which might wrap around a substrate to deliver it to CtpA for degradation. By structure-guided mutagenesis and functional assays, we also showed that the interfaces of the CtpA trimer of dimers and an N-terminal helix of LbcA are important for LbcA-mediated substrate degradation by CtpA both in vitro and in vivo. This work improves our understanding of the molecular mechanism of the LbcA-CtpA proteolytic system and reveals some striking differences from the arrangements found in some other bacterial CTPs. IMPORTANCE Carboxyl-terminal processing proteases (CTPs) are found in all three domains of life. In bacteria, some CTPs have been associated with virulence, raising the possibility that they could be therapeutic targets. However, relatively little is known about their molecular mechanisms of action. In Pseudomonas aeruginosa, CtpA supports virulence by working in complex with the outer membrane lipoprotein LbcA to degrade cell wall hydrolases. Here, we report structure-function analyses of CtpA and LbcA, which reveals that CtpA assembles into an inactive hexamer comprising a trimer of dimers. LbcA is monomeric, with the first N-terminal helix important for binding to and activating CtpA, followed by a spiral structure composed of 11 tetratricopeptide repeats, which could wrap around a substrate for delivery to CtpA. This work reveals a unique mutimeric arrangement for a CTP and insight into how the important LbcA-CtpA proteolytic system functions.

The global power demand is increasing year by year. Power quality fault recognition plays an important role in determining the fault type when a fault occurs, so as to maintain power quality and supply stability. Therefore, this paper proposed using the symmetrized dot pattern (SDP) algorithm plus the convolutional neural network (CNN) to study power quality fault recognition. Six common power quality fault models were taken as the subjects of discussion, including normal voltage, voltage sag, voltage swell, voltage interruptions, voltage flickers, and voltage harmonics. First, the voltage variation data of five cycles were extracted from a 60 Hz power supply and introduced into the SDP. Afterwards, the data were converted into graph data, which could be used for fault recognition. Lastly, the power quality fault type was identified by CNN. In this study, 600 random fault data (100 data per fault) were imported into the algorithm, and the recognition rate reached as high as 92.9%. Additionally, SDP could reduce the mass original data. After the subtle changes in the output signals were captured, they could be observed by images. The power quality fault state could thus be accurately recognized by CNN.

High integration of modern microwave circuits and systems puts forward higher requirements for multi-function and electromagnetic compatibility (EMC) performance of transmission channels. In this paper, we propose two EMC technologies including the substrate integrated packaging (SIP) and tuneable wavenumber mismatching (TWM) based on multi-functional spoof surface plasmon polariton (SSPP) channels. The SIP technology can effectively improve the EMC performance of the SSPP channels in the whole frequency band by designing the packaging structure with easy fabrication and compact size; while the TWM technology can significantly suppress crosstalks in desired frequency bands by manipulating the wavenumber difference between two adjacent channels. Simulated and measured results demonstrate excellent multi-function and EMC performance of the integrated multi-functional SSPP channels by employing the two EMC technologies. The integrated multi-functional SSPP channels can realize continuous phase modulation in X-band and continuous amplitude modulation in Ku-band. The coupling coefficient of the integrated channels is about 8–10 dB lower than that of the channels without the package, and is 13–15 dB lower than that of the traditional microstrip channels in the whole X-band and Ku-band. Meanwhile, the coupling coefficient of the integrated multi-functional SSPP channels with a distance of 1/30 λ _0 can be reduced to around −30 dB in the desired narrow bands. Therefore, the proposed EMC technologies may find broad applications in highly integrated microwave circuits and systems.

This research planned to dig the impacts and potential principles of long noncoding RNA RP4 onH9c2 cell injury induced by hypoxia. The H9c2 cardiac muscle cells were cultured under 3% O2 concentration to induce hypoxia injury, followed by detection of RP4 expression. RP4 was then overexpressed and silenced to investigate its effects on cell injury induced by hypoxia. The potential correlation between RP4 and miR-939, between miR-939 and Bnip3, and between RP4/miR-939/Bnip3 axis and Wnt/β-catenin pathway activation were explored. Biological processes (suppressed cell viability, migration and invasion, but enhanced cell apoptosis) were changed by hypoxia. Upregulation of RP4 enhanced hypoxia-produced damage in H9c2 cells. Additionally, miR-939 expression was opposite regulated by RP4, and miR-939 mimic abrogated the influences of pc-RP4 on enhanced hypoxia damage in H9c2 cells. Moreover, Bnip3 was targeted by miR-939 and their correlation is negative. Furthermore, upregulation of RP4 exacerbated hypoxia-produced injury in H9c2 cells by sensitizing Wnt/β-catenin signals in H9c2 cells, which was regulated by miR-939/Bnip3 axis. Our findings reveal that RP4 is highly expressed in the hypoxia-resulted H9c2 cells. Enhanced expression of RP4 may exacerbate hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3 axis-mediated briskness of Wnt/β-catenin signals. Our study will offer a fresh theoretical basis for the treatment of ischemic myocardial injury.

It has been recognized that rebalancing the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) helps relieve vascular injury. Presently, we aim to investigate whether long non-coding RNA (lncRNA) maternally expressed 8 (MEG8) plays a role in affecting the excessive proliferation and migration of VSMCs following hypoxia stimulation. A percutaneous transluminal angioplasty balloon dilatation catheter was adopted to establish vascular intimal injury, the levels of MEG8 and miR-195-5p in the carotid artery were tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Hypoxia was used to stimulate VSMCs, then the cell counting kit-8 (CCK-8) assay, Transnwell assay, and wound healing assay were conducted to evaluate the proliferation, and migration of VSMCs. The protein levels of RECK (reversion inducing cysteine rich protein with kazal motifs), MMP (matrix metalloproteinase) 3/9/13, COX2 (cytochrome c oxidase subunit II), macrophage inflammatory protein (MIP)-1beta, VCAM-1 (vascular cell adhesion molecule 1), ICAM-1 (intercellular adhesion molecule 1), and HIF-1α (hypoxia inducible factor 1 subunit alpha) were determined by western blot or cellular immunofluorescence. As the data showed, MEG8 was down-regulated in the carotid artery after balloon injury in rats and hypoxia-treated VSMCs, and miR-195-5p was overexpressed. Forced MEG8 overexpression or inhibiting miR-195-5p attenuated hypoxia-promoted cell proliferation and migration of VSMCs. In addition, miR-195-5p up-regulation reversed MEG8-mediated effects. Hypoxia hindered the RECK expression while boosted MMP3/9/13 levels, and the effect was markedly reversed with MEG8 up-regulation or miR-195-5p down-regulation. Mechanistically, MEG8 functioned as a competitive endogenous (ceRNA) by sponging miR-195-5p which targeted RECK. Moreover, the HIF-1α inhibitor PX478 prevented hypoxia-induced proliferation, and migration of VSMCs, upregulated MEG8, and restrained miR-195-5p expression. Overall, lncRNA MEG8 participated in hypoxia-induced excessive proliferation, inflammation and migration of VSMCs through the miR-195-5p/RECK axis.

CRISPR/Cas9 system has been used as the most powerful gene editing tool for precision medicine and advanced gene therapy. However, its wide applications are limited by the poor biosafety of lentivirus delivery vectors though with high-efficiency transduction. To construct a safer vector and promote genome integration, the CRISPR/Cas9 gene is cloned into a plasmid-based non-viral safe vector Sleeping-Beauty (SB) transposon in this study to obtain pT2SpCas9. Meanwhile, PDA/DEX-PEI@HA (PDPH) nanoparticles are constructed to facilitate the precise CRISPR/Cas9 targeting delivery, by using polydopamine (PDA) as the carrier, hyaluronic acid (HA) as the cell-targeting ligand and dexamethasone (DEX) as the nuclear localization signal (NLS). The results showed that PDPH could deliver pDNA efficiently into the cell and further into the nucleus. The transfection efficiency of PDPH is much higher than that of NPs without HA and DEX. Remarkably, the cytotoxicity of PDPH is negligible in comparison to PEI25k and PEI10k. Western blots showed that after the transfection of PDPH/pT2SpCas9-Nanog/SB11, Nanog protein in HeLa cells is knocked out, and the proliferation and migration abilities of tumor cells are significantly decreased. This study demonstrates that PDA/DEX-PEI25k@HA/pT2SpCas9 (PDPH25 K/pT2SpCas9) has the great potential as a non-viral gene vector for CRISPR/Cas9 delivery and clinical medication.

Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs.

Abstract Next‐generation inter‐chip communication requires ultrafast ultra‐compact interconnects. Designer plasmonics offers a possible route towards this goal. Further development of the plasmonic technique to circuit applications requires the direct amplification of plasmonic signals on a compact platform. However, significant signal distortions and limited operational speeds prevent the application of traditional MOS‐based amplifiers to plasmonics. Up to day, the amplification of surface plasmons without phase distortion has remained a scientific challenge. In this work, the concept of parametric amplification (PA) is transplanted to the plasmonics and is realized experimentally an ultrathin reconfigurable PA using a spoof surface plasmon polariton (SSPP) waveguide integrated with tunable and nonlinear varactors. The measured parametric gain in the experiment can reach up to 9.14 dB within a short nonlinear propagation length, for example, six SSPP wavelengths, in excellent agreement with the theoretical prediction. By tuning the bias voltage of varactors, the phase‐matching condition can be precisely controlled over a broad frequency band, enabling the authors to realize the multi‐frequency PA of plasmonic signals. Measured phase responses confirm that the plasmonic parametric amplifier can significantly suppress the signal distortions as compared with the traditional MOS‐based amplifier, which is a property highly desired for ultrafast wireless communication systems and integrated circuits.

In terms of mortality and survival, pancreatic cancer is one of the worst malignancies. Known as a unique type of programmed cell death, cuprotosis contributes to tumor cell growth, angiogenesis, and metastasis. Cuprotosis programmed-cell-death-related lncRNAs (CRLs) have been linked to PAAD, although their functions in the tumor microenvironment and prognosis are not well understood. This study included data from the TCGA-PAAD cohort. Random sampling of PAAD data was conducted, splitting the data into two groups for use as a training set and test set (7:3). We searched for differentially expressed genes that were substantially linked to prognosis using univariate Cox and Lasso regression analysis. Through the use of multivariate Cox proportional risk regression, a risk-rating system for prognosis was developed. Correlations between the CRL signature and clinicopathological characteristics, tumor microenvironment, immunotherapy response, and chemotherapy sensitivity were further evaluated. Lastly, qRT-PCR was used to compare CRL expression in healthy tissues to that in tumors. Some CRLs are thought to have strong correlations with PAAD outcomes. These CRLs include AC005332.6, LINC02041, LINC00857, and AL117382.1. The CRL-based signature construction exhibited outstanding predictive performance and offers a fresh approach to evaluating pre-immune effectiveness, paving the way for future studies in precision immuno-oncology.

Low-grade glioma (LGG) is a highly aggressive disease in the skull. On the other hand, anoikis, a specific form of cell death induced by the loss of cell contact with the extracellular matrix, plays a key role in cancer metastasis. In this study, anoikis-related genes (ANRGs) were used to identify LGG subtypes and to construct a prognostic model for LGG patients. In addition, we explored the immune microenvironment and enrichment pathways between different subtypes. We constructed an anoikis-related gene signature using the TCGA (The Cancer Genome Atlas) cohort and investigated the differences between different risk groups in clinical features, mutational landscape, immune cell infiltration (ICI), etc. Kaplan–Meier analysis showed that the characteristics of ANRGs in the high-risk group were associated with poor prognosis in LGG patients. The risk score was identified as an independent prognostic factor. The high-risk group had higher ICI, tumor mutation load (TMB), immune checkpoint gene expression, and therapeutic response to immune checkpoint blockers (ICB). Functional analysis showed that these high-risk and low-risk groups had different immune statuses and drug sensitivity. Risk scores were used together with LGG clinicopathological features to construct a nomogram, and Decision Curve Analysis (DCA) showed that the model could enable patients to benefit from clinical treatment strategies.

This study proposes an optical front-end for wideband transceivers based on photonic time compression (PTC) and photonic time stretch (PTS) techniques. The PTC and PTS systems within a transceiver generate and receive wideband RF signals, respectively, which expand the processible signal bandwidth. We present analytical models for characterizing the optical front-end based on the PTC and PTS. The design of the front-end for signal generation and reception is also discussed, in which we emphasize the bandwidth match between the PTC-based transmitter and PTS-based receiver through an appropriate dispersion configuration. We conducted experiments on PTC and PTS systems with a single channel. Further simulation results for PTC and PTS systems with multiple channels for continuous-time operation are presented. The proposed front-end based on time compression/stretch can largely improve the signal bandwidth in systems using inexpensive low-speed analogue/digital converters.

Background The abnormal upregulation of programmed death-ligand 1 (PD-L1) in cancer cells inhibits T cell-mediated cytotoxicity, but the molecular mechanisms that drive and maintain PD-L1 expression are still incompletely understood.Methods Combined analyses of genomes and proteomics were applied to find potential regulators of PD-L1. In vitro experiments were performed to investigate the regulatory mechanism of PD-L1 by thyroid adenoma associated gene (THADA) using human colorectal cancer (CRC) cells. The prevalence of THADA was analyzed using CRC tissue microarrays by immunohistochemistry. T cell killing assay, programmed cell death 1 binding assay and MC38 transplanted tumor models in C57BL/6 mice were developed to investigate the antitumor effect of THADA.Results THADA is critically required for the Golgi residency of PD-L1, and this non-redundant, coat protein complex II (COPII)-associated mechanism maintains PD-L1 expression in tumor cells. THADA mediated the interaction between PD-L1 as a cargo protein with SEC24A, a module on the COPII trafficking vesicle. Silencing THADA caused absence and endoplasmic reticulum (ER) retention of PD-L1 but not major histocompatibility complex-I, inducing PD-L1 clearance through ER-associated degradation. Targeting THADA substantially enhanced T cell-mediated cytotoxicity, and increased CD8+ T cells infiltration in mouse tumor tissues. Analysis on clinical tissue samples supported a potential role of THADA in upregulating PD-L1 expression in cancer.Conclusions Our data reveal a crucial cellular process for PD-L1 maturation and maintenance in tumor cells, and highlight THADA as a promising target for overcoming PD-L1-dependent immune evasion.

Background: Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults and is highly metastatic, resulting in a poor patient prognosis. Sphingolipid metabolism plays an important role in tumor development, diagnosis, and prognosis. This study aimed to establish a reliable signature based on sphingolipid metabolism genes (SMGs), thus providing a new perspective for assessing immunotherapy response and prognosis in patients with UVM. Methods: In this study, SMGs were used to classify UVM from the TCGA-UVM and GEO cohorts. Genes significantly associated with prognosis in UVM patients were screened using univariate cox regression analysis. The most significantly characterized genes were obtained by machine learning, and 4-SMGs prognosis signature was constructed by stepwise multifactorial cox. External validation was performed in the GSE84976 cohort. The level of immune infiltration of 4-SMGs in high- and low-risk patients was analyzed by platforms such as CIBERSORT. The prediction of 4-SMGs on immunotherapy and immune checkpoint blockade (ICB) response in UVM patients was assessed by ImmuCellAI and TIP portals. Results: 4-SMGs were considered to be strongly associated with the prognosis of UVM and were good predictors of UVM prognosis. Multivariate analysis found that the model was an independent predictor of UVM, with patients in the low-risk group having higher overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores had good prognostic power. The high-risk group showed better results when receiving immunotherapy. Conclusions: 4-SMGs signature and nomogram showed excellent predictive performance and provided a new perspective for assessing pre-immune efficacy, which will facilitate future precision immuno-oncology studies. [ABSTRACT FROM AUTHOR]

The heterodimeric eukaryotic Drs2p-Cdc50p complex is a lipid flippase that maintains cell membrane asymmetry and its autoinhibition is released by PI4P binding. Here authors show cryo-EM structures of Drs2p-Cdc50p in apo and PI4P-activated form which reveal the structural changes upon PI4P binding.

AIM: To investigate whether the gene variants in MYOC and ABCA1 are associated with primary angle-closure glaucoma (PACG) and anterior chamber depth (ACD) and axial length (AL) in samples from northern China. METHODS: The present case-control association study consisted of 500 PACG patients and 720 unrelated controls. Each participant was genotyped for eleven single nucleotide polymorphisms (SNPs) in MYOC and ABCA1 genes (rs12076134, rs183532, rs235875 and rs235913 in MYOC, rs2422493, rs2487042, rs2472496, rs2472493, rs2487032, rs2472459 and rs2472519 near ABCA1) using an improved multiplex ligation detection reaction (iMLDR) technique. The genetic association analyses were performed by PLINK using a logistic regression model. The association between genotypes and ocular biometric parameters was performed by SPSS using generalized estimation equation. Bonferroni corrections were implemented and the statistical power was calculated by the Power and Sample Size Calculation. RESULTS: Two SNPs rs183532 and rs235875 as well as a haplotype TTC in MYOC were nominally associated with PACG despite the significance was lost after Bonferroni correction. No association was observed between ABCA1 and PACG, neither did the association between these variants and ACD as well as AL. CONCLUSION: The present study suggests MYOC and ABCA1 do not play a part in the pathogenesis of PACG as well as the regulation of ocular biometric parameters in a northern Chinese population. Further investigations with large sample size are needed to verify this consequence.

The identification of cross-linked peptides at a proteome scale for interactome analyses represents a complex challenge. Here the authors report an efficient and reliable search engine pLink 2 for proteome-scale cross-linking mass spectrometry analyses, and demonstrate how to systematically evaluate the credibility of search engines.

Abstract Background Immune checkpoint inhibitors (ICPIs), used to treat different advanced malignancies, are associated with a wide range of immune-related adverse reactions (irAEs) that deserve close monitoring of patients. Gastrointestinal reactions and hepatotoxicity may occur, which warrant careful evaluation to confirm the etiology and attribution to ICPIs as these events could affect future management. Case presentation We describe a case of a patient with prostate adenocarcinoma, treated with dual ICPIs comprised of ipilimumab and nivolumab, who developed elevated liver enzymes in the context of infliximab therapy prescribed to treat gastrointestinal irAE from his ICPIs. The patient’s grade 3 colitis became steroid-refractory, requiring a one-time infusion of infliximab, a biologic agent used commonly in inflammatory bowel disease, as a rescue therapy, to which he responded. The patient subsequently developed liver injury. This presented a diagnostic dilemma involving differential diagnoses of hepatotoxicity due to ICPI or infliximab exposure. A careful review of the clinical history, evaluation of the chronology of events, and exclusion of other causes of acute hepatitis were employed to make the final diagnosis of this event as infliximab-associated hepatotoxicity. Conclusion ICPIs such as CTLA-4 and PD-1 inhibitors have the potential to cause both gastrointestinal reactions and hepatotoxicity. An additional confounding factor in our patient’s case was the exposure to infliximab used to manage an established irAE that developed after the last exposure to ICPIs. The clinical history and data supported infliximab-associated hepatotoxicity, rather than an irAE. With the increasing application of ICPIs for different cancers, in conjunction with potential risks for irAE, the liver profile should be closely monitored during treatment with ICPI as well as with anti-TNF-α agents in this patient population.

In this paper a novel photonic digitization scheme with differential encoding based on orthogonal vector superposition (OVS) is proposed and demonstrated. A phase modulator (PM) and two delay-line interferometers (DLIs) with π/2 difference in bias phase are employed to generate two orthogonal modulated signals. By adjusting and combining the intensity of two orthogonal signals with an OVS module, the desired phase shifts among different transfer functions can be obtained. The proposed scheme can differentially encode the input signal with enhanced bit resolution. Compared with the existing photonic digitization schemes based on modulators, this scheme features its simple configuration, because only a single PM, two DLIs and an OVS module are required; moreover, since the desired phase shifts of transfer functions are realized by attenuating the signal intensities, the proposed scheme can effectively alleviate the problem of phase bias drift induced by modulators. Proof-of-concept experiments of 3- and 4-bit photonic digitization systems based on OVS are successfully carried out, which demonstrate the feasibility of the approach.

Compressive sensing (CS) with photonic technologies provides a promising way to acquire information with reduced measurement. Photonic CS with pulse stretch and compression has been proved to be capable of capturing wideband time-domain signals at extremely high equivalent sampling rate or images at high frame rate. In this approach, an input short pulse is first stretched by propagating through a dispersive medium and then the stretched pulse is modulated by a signal to be measured and a pseudorandom bit sequence (PRBS). The stretched pulse encoded with the signal and the PRBS is compressed in the time domain after passing a second dispersive medium with an opposite dispersion value. The time-domain compression of the stretched pulse was regarded as the integration function in the CS process (but it has never been proved), which is a key to realize time-domain downsampling or single-pixel imaging. In this paper, we fully investigate the theoretical framework of the photonic CS with optical pulse stretch and compression, and present an analytical model of the CS measurement matrix based on the analysis of the pulse stretch, modulation and compression, for the first time to our knowledge. Moreover, we prove the equivalence between the peak value of the compressed pulse and the integral value of the mixed signal, which is the basis of the analytical model. In addition, we further discuss the impact of the limited bandwidth of the employed photodetector on the measurement and the performance of signal reconstruction.

The crosstalk suppression of multichannel coupled drivelines is studied for high-performance integration of micro-electro-mechanical system arrays. By using traditional drivelines, for example, microstrip lines, the distance between adjacent drivelines should be large enough to reduce the multichannel coupling effects. As a result, the size and the area of ultra-low crosstalk and closed-packaged driveline become an issue for design. To address it, we proposed a new scheme of multichannel spoof surface plasmon polaritons (SSPP)-based drivelines. The new drivelines consist of multiple parallel planar corrugated metallic strips. Thanks to the strong field confinement and localization characteristics of the SSPPs, the coupling effects between drivelines in different channels can be significantly suppressed with no need of any other coupling suppression circuits. For demonstration and investigation, both simulation and measurement are carried out up to 20 GHz. The results show that the crosstalk by using the proposed new drivelines can be reduced by about 10 dB on average. Therefore, the SSPP-based multichannel drivelines would be a good candidate for large-scale advanced integrated devices and systems with requirements of both miniaturization and coupling suppression.

Temporal Talbot phenomena occur when a periodic optical pulse train propagates through a dispersive medium with a proper dispersion amount, which includes integer and fractional orders depending on the dispersion amount. The fractional temporal Talbot (FTT) effect has attracted great interest because of its potentials in repetition rate multiplication of optical pulse train and passive amplification of short pulses. In this paper, we investigate the evolution of amplitude fluctuation in FTT systems from the viewpoint of the frequency-dependent fading of pulse train envelope. It is found that the envelope frequency response of FTT is different from that of integer orders since there is waveform-to-waveform phase profile in the output pulse train in FTT systems. The noise reduction phenomenon in FTT systems is analyzed based on the derived frequency response. A closed-form expression of the noise reduction ratio is derived for the first time based on the analysis of the noise power spectral density. With the given model, we are able to predict the fluctuation suppression effect in FTT systems more precisely.

For the future high-speed next-generation Ethernet passive optical network (NG-EPON) system, the low-cost system could be kept by adopting low bandwidth devices. To compensate for the signal distortion and improve the performance of high-speed bandwidth limited system, we propose a special feature vector construction to achieve a new equalizer scheme based on support vector machines (SVM) classifier. For the first time, we mathematically analyze the model of the bandwidth-limited optical transmission system and theoretically derive the linear separability of the proposed feature vector formed linear hyperplane in 100-Gb/s NG-EPON system. Furthermore, 4 × 25-Gb/s non-return to zero (NRZ) and 2 × 50-Gb/s four-level pulse amplitude modulation (PAM-4) per wavelength transmission experiments with 10-G class optics system are demonstrated to prove the feasibility of our scheme. The experimental results show that, for 25-Gb/s/λ NRZ transmission, compared to the decision feedback equalizer (DFE) and feed-forward equalizer (FFE), the receiver sensitivity achieved by our scheme can be improved by about 0.5-dB @BER=3.8e-3 with limited training sequence. For the 50-Gb/s/λ PAM-4 case, the SVM-based equalization method improves the receiver sensitivity for about 1-dB.

The plasmonic surface is made of metallic surface with deep sub-wavelength decorations, which are designed to mimic the surface plasmon polaritons at lower frequency. Recently, high-order modes in some special structures are analyzed. In order to analyze the dispersion problem of high-order modes of complex lossless structures faster and simpler, a convenient and simple method using the average input wave impedance obtained by a field-network joint solution is proposed. Meanwhile, based on Forster's reactance theorem, high-order modes of the complex structure always exist. Then, the dispersion curves of the high-order modes calculated using proposed method are in perfect match with the simulated results, which can verify the effectiveness and correctness of the proposed method. Additionally, the simulated and experimentally measured electric field distribution of high-order modes have great agreement. Using the proposed method, one can quickly obtain dispersion curve of a plasmonic structure to verify or estimate structure design. Hence, the proposed method may make a big step forward for obtaining the special dispersion relations.