Time Sequence Analysis Research Articles

Modeling multi-object interactions using “string of feature graphs”

In this paper, a novel generalized framework of activity representation and recognition based on a ‘string of feature graphs (SFG)’ model is introduced. The proposed framework represents a visual activity as a string of feature graphs, where the string elements are initially matched using a graph-based spectral technique, followed by a dynamic programming scheme for matching the complete strings. The framework is motivated by success of time sequence analysis approaches in speech recognition, but modified in order to capture the spatio-temporal properties of individual actions, the interactions between objects, and speed of activity execution. This framework can be adapted to various spatio-temporal motion features, and we show details on using STIP features and track features. Furthermore, we show how this SFG model can be embedded within a switched dynamical system (SDS) that is able to automatically choose the most efficient features for a particular video segment. This allows us to analyze a variety of activities in natural videos in a computationally efficient manner. Experimental results on the basic SFG model as well as its integration with the SDS are shown on some of the most challenging multi-object datasets available to the activity analysis community.

Application Study of Load Forecasting of Central Air-Conditioning System Based on Time Sequence Analysis Method

With the characteristics of non-stationarity, non-linearity, time-lag of refrigeration/ heating supplying in minds, load forecasting of central air-conditioning system is carried using time sequence analysis method. Firstly, acquisition sample data of central air-conditioning system is pretreated, and random time sequence AR model of system is formulated. Then, forecasting of AR refrigeration/heating load based on Yule-walker method is conducted. In order to enhance forecasting accuracy, crossover forecasting is introduced into the load forecasting, that is, to use vertical forecasting to follow household demands for load and horizontal forecasting to track changes of weather. Then, weight cross is made to vertical and horizontal forecasting results. Finally, refrigeration/heating load forecasting software of central air-conditioning system is developed, which is used in energy-saving monitoring and control of central air-conditioning system.

Serum levels of anti‐type VII collagen antibodies detected by enzyme‐linked immunosorbent assay in patients with epidermolysis bullosa acquisita are correlated with the severity of skin lesions

Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune subepidermal bullous disease characterized by circulating autoantibodies against type VII collagen. Detecting these autoantibodies is crucial for the diagnosis of this disease, and is also useful for measuring disease activity. Enzyme-linked immunosorbent assay (ELISA), a quantitative method to measure anti-type VII collagen antibody levels, is currently available to diagnose EBA. The aim of this study was to investigate the relationship of ELISA with overall clinical severity. Sera from patients with EBA (n = 30), bullous pemphigoid (n = 20), anti-laminin γ1 pemphigoid (n = 9) and healthy donors (n = 24) were tested using ELISA, using the recombinant non-collagenous 1 (NC1) and 2 (NC2) domains of type VII collagen. Relationships between clinical characteristics, indirect immunofluoroscence (IIF) titres and ELISA values were investigated. The sensitivity and specificity of the EBA ELISA were 96.7% and 98.1%, respectively. There was no significant difference between ELISA results for classic and inflammatory types. The severity of skin involvement was positively correlated with both ELISA value (r = 0.87, P < 0.01) and IIF titre (r = 0.59, P < 0.01). Time sequence analysis in four patients with EBA showed that ELISA values reflect disease activity better than IIF titres. Type VII collagen ELISA using the NC1 and NC2 domains is useful for diagnosing EBA and monitoring disease severity.

A Study on the State Recognition of Frame Structure Based on the Maximum Lyapunov Exponent

Based on the analysis of chaotic time sequence and the characterization to the system chaotic property from it’s characteristic index, we established finite element model about ASCE Benchmark. Then we got 4 acceleration time sequence of Benchmark model by simulation of instantaneous excitation. At last, we made a experimental analysis on the maximum Lyapunov exponent. As the result shows, all maximum Lyapunov exponents are above zero. It means that chaotic phenomenon appears in the structure system. At the same time, maximum Lyapunov exponent shows it’s sensitivity along with the evolution of structural condition. That is to say, the statement of structure could be reflected by the chaotic index of chaotic time sequence. Then we get new ideas on the study of safety assessment relied on the structural health monitoring.

Automated Pedestrian Detection and Recognition Applied to Automatic Gate Machines in Urban Rail Transit

This paper presents a novel pedestrian detection and recognition method based on a new photoelectric sensor layout for increasing the recognition rate and the recognition speed of the Automatic Gate Machine (AGM). First of all, a new sensors layout is designed. Next, by collecting the time and sequence of pedestrian breaking the rays of the sensors, an algorithm of combining the time sequence analysis and event analysis is developed to detect and judgment the legality of the pedestrians so that the gate of the AGM is either opened or closed. Then, the algorithm is implemented by software method and FPGA method respectively. Finally, the experiments on the prototype of AGM prove that the recognition rate and the recognition speed are increased effectively.

Germination potential index of Sindh rice cultivars on biochemical basis, using amylase as an indicator

Time sequence analysis of germination and vigor of five rice cultivars were carried out by investigating the associated biochemical changes. The experiments were conducted with varying periods of incubation for germination and varietal differences were observed for different parameters. Alpha amylase activities were found to be directly correlated with germination percentage. Gradual increase in reducing sugars along with α-amylase activity was observed, while total carbohydrates decreased as germination proceeded. The genetic variability of seed vigor of rice cultivars may be attributed to varietal differences of α-amylase activity at different stages of germination. Simultaneous increase in reducing sugars due to degradation of reserve carbohydrates was observed. The results indicated that α-amylase activity is a biochemical indicator showing different germination abilities of rice varieties, leading to different seed vigor. Among all five seed cultivars, SADA HAYAT demonstrated maximum seed vigor and alpha amylase activity along with germination period. This cultivar shows a potential for maximum production for successful breeding program.

Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations

Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirm MLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin.

Magnifying lens for 800 MeV proton radiography

This article describes the design and performance of a magnifying magnetic-lens system designed, built, and commissioned at the Los Alamos National Laboratory (LANL) for 800 MeV flash proton radiography. The technique of flash proton radiography has been developed at LANL to study material properties under dynamic loading conditions through the analysis of time sequences of proton radiographs. The requirements of this growing experimental program have resulted in the need for improvements in spatial radiographic resolution. To meet these needs, a new magnetic lens system, consisting of four permanent magnet quadrupoles, has been developed. This new lens system was designed to reduce the second order chromatic aberrations, the dominant source of image blur in 800 MeV proton radiography, as well as magnifying the image to reduce the blur contribution from the detector and camera systems. The recently commissioned lens system performed as designed, providing nearly a factor of three improvement in radiographic resolution.

Correlation between low-frequency current-noise enhancement and high-frequency oscillations in GaN-based planar nanodiodes: A Monte Carlo study

We present a spectral analysis of time sequences of current, calculated by means of Monte Carlo simulations, in GaN-based asymmetric nanodiodes, devices that are potential candidates to exhibit Gunn oscillations. It is found that the low-frequency noise increases significantly for biases close to the threshold voltage of Gunn oscillations, taking place at much higher frequencies of hundreds of gigahertz. Due to the inherent difficulty in detecting so fast fluctuations, the measurement of the low-frequency noise can be a quite useful tool for predicting current oscillations at sub-terahertz frequencies in these devices.

A wavelet‐based spectral method for extracting self‐similarity measures in time‐varying two‐dimensional rainfall maps

Many environmental time‐evolving spatial phenomena are characterized by a large number of energetic modes, the occurrence of irregularities, and self‐organization over a wide range of space or time scales. Precipitation is a classical example characterized by both strong intermittency and multiscale dynamics, and these features generate persistence, long‐range dependence, and extremes (whether be it droughts or extreme floods). Over the last two decades, time‐frequency or time‐scale transforms have become indispensable tools in the analysis of such phenomena and, as a consequence, a number of wavelet‐based spectral methods are now routinely employed to estimate Hurst exponents and other measures of regularity and scaling. In this article, an ensemble of new wavelet‐based spectral tools for analysis of 2‐D images is proposed. The new scale‐mixing wavelet spectrum is applied to the analysis of time sequences of two‐dimensional spatial rainfall radar images characterized by either convective or frontal systems. Intermittent spatial patterns connected to the precipitation‐formation mechanisms were encoded in low‐dimensional informative descriptors appropriate for classification, discrimination analyses and possible integration with climate models. We found that convective rainfall spatial patterns compared to frontal patterns produce spectral signatures consistent with their generation mechanism.

Abstract 6: S1, a Bid-like BH3 mimetic, induces apoptosis by dynamic change of Mcl-1 and dependent on Bak, not Bax

Abstract Mcl-1 is a unique anti-apoptotic member of Bcl-2 family. Its expression has been demonstrated to seriously impede the most authentic BH3 mimetic ABT-737-induced apoptosis in multiple cancer cell lines. S1, which has been previously identified as a pan-Bcl-2 inhibitor and pure BH3 mimetic by our group, was investigated here to challenge Mcl-1's protection. Cell viability assay and apoptosis assay showed S1 exhibits robust anticancer effectiveness in three selected ABT-737-resistant cancer cell lines, SMMC-7721, HCT116 and K562 cells. In contract with ABT-737, S1-induced apoptosis is regardless of the baseline of Mcl-1 expression. Interestingly, it dynamically modulates Mcl-1 through a combination of proteasome and caspase-mediated pathway and this dynamical change is associated well with the resistance, apoptosis onset, and apoptosis burst out induced by S1. To investigate how Mcl-1 dynamics is related with apoptosis at molecular level, we performed time-sequence and dose-dependent analysis of cell viability, western blot, and co-immunoprecipitation experiments. We found the trafficking of Bcl-2 family members determines Mcl-1 dynamical change and in turn apoptosis. First of all S1 untethers Bax and Bim from Bcl-2, but Bim shifts to Mcl-1 which stabilizes Mcl-1 and enforces the binding with Bak. Only when Bak is released by enough dose of S1 or enough exposure time is Mcl-1 downregualted to allow apoptosis occur. Using shRNA, we identified both S1-induced apoptosis and Mcl-1 dynamical modulation depend on Bak, not Bax. As such, much distinct function of Bax and Bak in the S1-induced pathway was illustrated. While Bax can be fully compensated for by Bak, Bak could be partly compensated for by Bax. Consistently, Bax-deficient DU145 cell is sensitive to S1, whereas Bak-mutant MKN-28 cells is much more resistant. NMR analyses revealed that S1 highly mimic tBid to target the BH3-binding pocket of Mcl-1. Cytochrome c release assay in purified DU145 mitochondrial testified a nicely structural-to-functional mimic of tBid, but not Bim. The Bid-like property is also consistent with its Bak-dependent apoptosis induction. The in vitro model could be extended to an in vivo mouse xenograft model that S1 induces apoptosis through Mcl-1 dynamical modulation and released Bak is the biomarker of apoptosis. In conclusion, S1 could be a highly potent therapeutic molecule for the treatment of Mcl-1-driven cancer cells with a mechanism-based model. Bak could serve as a biomarker to specify cancer cells sensitive to S1. In addition, the highly tBid/Mcl-1 binding mimic property could be used to probe the sophisticated network of Bcl-2 family. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 6. doi:10.1158/1538-7445.AM2011-6

Impact of International Nosocomial Infection Control Consortium (INICC) Strategy on Central Line–Associated Bloodstream Infection Rates in the Intensive Care Units of 15 Developing Countries

The International Nosocomial Infection Control Consortium (INICC) was established in 15 developing countries to reduce infection rates in resource-limited hospitals by focusing on education and feedback of outcome surveillance (infection rates) and process surveillance (adherence to infection control measures). We report a time-sequence analysis of the effectiveness of this approach in reducing rates of central line-associated bloodstream infection (CLABSI) and associated deaths in 86 intensive care units with a minimum of 6-month INICC membership. Pooled CLABSI rates during the first 3 months (baseline) were compared with rates at 6-month intervals during the first 24 months in 53,719 patients (190,905 central line-days). Process surveillance results at baseline were compared with intervention period data. During the first 6 months, CLABSI incidence decreased by 33% (from 14.5 to 9.7 CLABSIs per 1,000 central line-days). Over the first 24 months there was a cumulative reduction from baseline of 54% (from 16.0 to 7.4 CLABSIs per 1,000 central line-days; relative risk, 0.46 [95% confidence interval, 0.33-0.63]; P < .001). The number of deaths in patients with CLABSI decreased by 58%. During the intervention period, hand hygiene adherence improved from 50% to 60% (P < .001); the percentage of intensive care units that used maximal sterile barriers at insertion increased from 45% to 85% (P < .001), that adopted chlorhexidine for antisepsis increased from 7% to 27% (P < .001), and that sought to remove unneeded catheters increased from 37% to 83% (P < .001); and the duration of central line placement decreased from 4.1 to 3.5 days (P < .001). Education, performance feedback, and outcome and process surveillance of CLABSI rates significantly improved infection control adherence, reducing the CLABSI incidence by 54% and the number of CLABSI-associated deaths by 58% in INICC hospitals during the first 2 years.

A Novel Network Service Mode of Geospatial Information and its Prototype System

This paper proposes a novel digital earth platform framework, which is a application, service and decision-making support systems of geospatial data acquisition, storage, transmission, conversion, processing, analysis, retrieval, expression and output as a unified body, the core of which is to deal with geospatial data for spatial geographic information network service Geo-Browser/Geospatial Information Server (G/S) mode and Hyper Geographic Markup Language (HGML). Depth understanding and analysis of platform architecture, this paper realizes of digital earth platform prototype – U-Star based on the geospatial information network service G/S mode, the platform has the merits of C/S mode that full use of client resources, efficient to deal with the client data, as well as the advantages of B/S mode that the unified client and convenient to access network. This platform is a new server which can cope with massive geospatial information and a solution which can provide efficient service. It has already been applied into many fields, such as the digital tourism service system, the time sequence analysis of Wenchuan Earthquake, the real-time video monitoring based on the digital earth platform and the intelligent processing and exhibition of remote sensing data. The result indicates that the perfection of space, time and complexion of the geospatial information network accessing will effectively improve the quality and efficiency of the shared data, which has very important theoretical significance and bright prospect of application.

Shear-induced lamellar ionic liquid-crystal foam

In a recent paper we reported an experimental study of two N-alkylimidazolium salts. These ionic compounds exhibit liquid crystalline behaviour with melting points above 50°C in bulk. However, if they are sheared, a (possibly non-equilibrium) lamellar phase forms at room temperature. Upon shearing a thin film of the material between microscope slides, textures were observed that are strikingly similar to liquid (wet) foams. The images obtained from polarising optical microscopy (POM) were found to share many of the known quantitative properties of a two-dimensional foam coarsening process. Here we report an experimental study of this foam using a shearing system coupled with POM. The structure and evolution of the foam are investigated through the image analysis of time sequences of micrographs obtained for well-controlled sets of physical parameters (sample thickness, shear rate and temperature). In particular, we find that there is a threshold shear rate below which no foam can form. Above this threshold, a steady-state foam pattern is obtained where the mean cell area generally decreases with increasing shear rate. Furthermore, the steady-state internal cell angles and distribution of the cell number of sides deviate from their equilibrium (i.e. zero-shear) values.

Hidden Markov Model for Multi-Thread Programs Time Sequence Analysis

PDF HTML阅读 XML下载 导出引用 引用提醒 多线程程序时序分析的隐Markov模型 DOI: 作者: 作者单位: 作者简介: 通讯作者: 中图分类号: 基金项目: Supported by the National High-Tech Research and Development Plan of China under Grant No.2006AA01Z449 (国家高技术研究发展计划(863)) Hidden Markov Model for Multi-Thread Programs Time Sequence Analysis Author: Affiliation: Fund Project: 摘要 | 图/表 | 访问统计 | 参考文献 | 相似文献 | 引证文献 | 资源附件 | 文章评论 摘要:针对多线程程序数据竞争分析与检测困难的问题,提出一种基于隐Markov 模型的多线程程序时序分析方法.用随机变量不确定性刻画不同线程之间时序上的交互关系,分析数据竞争条件下程序不确定结果的概率分布情况;建立多线程程序时序分析的隐Markov 模型,使用Baum-Welch 和前向算法仿真上下文对程序实际运行状态的影响.实验结果表明,该模型能够快速有效反映多线程执行时序,用于指导多线程程序时序竞争检测过程. Abstract:To overcome the difficulty of analyzing and detecting the data race in multithread programs, a method based on Hidden Markov model is presented for the analysis of time sequences in multithread programs. The random variable uncertainty is used to depict the mutual influence in different multithread in time sequences, and the probability distribution for random variable uncertainty is analyzed as the outcome of multithread programs on the condition of data race. Hidden Markov model is constructed to appreciate the state for the thread running according to the observed values of the running threads. The Baum-Welch and forwarding algorithm are used to simulate the real running process of the programs in the influence of context. It is proved by experiments that HMM model can quickly and effectively reflect the time sequence of the multithread programs, which can be used to instruct the detecting process of multithread programs. 参考文献 相似文献 引证文献

A MIF haplotype is associated with the outcome of patients with severe sepsis: a case control study.

BackgroundMacrophage migration inhibitory factor (MIF) plays an important regulatory role in sepsis. In the promoter region a C/G single nucleotide polymorphism (SNP) at position -173 (rs755622) and a CATT5-8 microsatellite at position -794 are related to modified promoter activity. The purpose of the study was to analyze their association with the incidence and outcome of severe sepsis.MethodsGenotype distributions and allele frequencies in 169 patients with severe sepsis, 94 healthy blood donors and 183 postoperative patients without signs of infection or inflammation were analyzed by real time PCR and Sequence analysis. All included individuals were Caucasians.ResultsGenotype distribution and allele frequencies of severe sepsis patients were comparable to both control groups. However, the genotype and allele frequencies of both polymorphisms were associated significantly with the outcome of severe sepsis. The highest risk of dying from severe sepsis was detectable in patients carrying a haplotype with the alleles -173 C and CATT7 (p = 0.0005, fisher exact test, RR = 1,806, CI: 1.337 to 2.439).ConclusionThe haplotype with the combination of the -173 C allele and the -794 CATT7 allele may not serve as a marker for susceptibility to sepsis, but may help identify septic patients at risk of dying.

Titanium dioxide nanoparticles induce apoptosis through the JNK/p38-caspase-8-Bid pathway in phytohemagglutinin-stimulated human lymphocytes

We investigated the signaling pathways underlying nano-TiO2-induced apoptosis in cultured human lymphocytes. Nano-TiO2 increased the proportion of sub-G1 cells, activated caspase-9 and caspase-3, and induced caspase-3-mediated PARP cleavage. Nano-TiO2 also induced loss of mitochondrial membrane potential, which suggests that nano-TiO2 induces apoptosis via a mitochondrial pathway. A time-sequence analysis of the induction of apoptosis by nano-TiO2 revealed that nano-TiO2 triggered apoptosis through caspase-8/Bid activation. We also observed that inhibition of caspase-8 by z-IETD-fmk suppressed the caspase-8/Bid activation, caspase-3-mediated PARP cleavage, and apoptosis. Nano-TiO2 activated two MAPKs, p38 and JNK. In addition, the selective p38 inhibitor SB203580 and selective JNK inhibitor SP600125 suppressed nano-TiO2-induced apoptosis and caspase-8 activation to moderate and significant extents, respectively. Knockdown of protein levels of JNK1 and p38 using an RNA interference technique also suppressed caspase-8 activation. Our results suggest that nano-TiO2-induced apoptosis is mediated by the p38/JNK pathway and the caspase-8-dependent Bid pathway in human lymphocytes.

The impact and durative effect of the measures of securing quality air for the Beijing Olympic and Paralympics Games 2008 on air pollution index in Beijing

To analyze the impact of the measures for securing quality air for the 2008 Beijing Olympic and Paralympics Games on air pollution index (API) in Beijing and forecast the aftereffects. The time-distribution of API in Beijing from 2004 to 2008 was described. The time sequence analysis was used and the autoregressive integrated moving average model (ARIMA) was chosen to establish an API forecasting model to predict the API in December, 2008. From 2004 to 2008, the average API in March (120 +/- 66) was the highest followed by November (116 +/- 72) and the average API in July (83 +/- 28) was the lowest followed by August (77 +/- 27). The proportion of "excellent" and "good" days from 2004 to 2008 were 9.56% (35/366), 54.37% (199/366), 8.49% (31/365), 54.52% (199/365), 7.12% (26/365 ), 58.90% (215/365 ), 8.77% (32/365), 58.63% (214/365), 16.67% (61/366), 58.20% (213/366) respectively, with an increasing trend year by year (chi2(trend) = 11.397, P = 0.001). The model of ARIMA (1, 0, 0) fitted well; according to the prediction of the ARIMA (1, 0, 0) model, the decrease of API that attributed to interim measures during the Olympic Games was 37. 1% and the average API of December was 82. The interim measures during the Olympic Games were effective on promoting air quality. After the Olympic Games, air quality would still remain good.

Comparison of 12 deformable registration strategies in adaptive radiation therapy for the treatment of head and neck tumors

Background and purpose Weight loss, tumor shrinkage, and tissue edema induce substantial modification of patient’s anatomy during head and neck (HN) radiotherapy (RT) or chemo-radiotherapy. These modifications may impact on the dose distribution to both target volumes (TVs) and organs at risk (OARs). Adaptive radiotherapy (ART) where patients are re-imaged and re-planned several times during the treatment is a possible strategy to improve treatment delivery. It however requires the use of specific deformable registration (DR) algorithms that requires proper validation on a clinical material. Materials and methods Twelve voxel-based DR strategies were compared with a dataset of 5 patients imaged with computed tomography (CT) before and once during RT (on average after a mean dose of 36.8 Gy): level-set (LS), level-set implemented in multi-resolution (LS MR), Demons’ algorithm implemented in multi-resolution (D MR), D MR followed by LS (D MR-LS), fast free-form deformable registration via calculus of variations (F3CV) and F3CV followed by LS (F3CV-LS). The use of an edge-preserving denoising filter called “local M-smoothers” applied to the registered images and combined to all the aforesaid strategies was also tested (fLS, fLS MR, fD MR, fD MR-LS, fF3CV, fF3CV-LS). All these strategies were compared to a rigid registration based on mutual information (MI, fMI). Chronological and anti-chronological registrations were also studied. The various DR strategies were evaluated using a volume-based criterion (i.e. Dice similarity index, DSI) and a voxel-intensity criterion (i.e. correlation coefficient, CC) on a total of 18 different manually contoured volumes. Results For the DSI analysis, the best three strategies were D MR, fD MR-LS, and fD MR, with the median values of 0.86, 0.85 and 0.85, respectively; corresponding inter-quartile range (IQR) reached 9.6%, 10% and 10.2%. For the CC analysis, the best three strategies were fD MR-LS, D MR-LS and D MR with the median values of 0.97, 0.96 and 0.94, respectively; corresponding IQR reached 11%, 9% and 15%. Concerning the time-sequence analysis, the anti-chronological registration (all deformable strategies pooled) showed a better median DSI value (0.84 vs 0.83, p < 0.001) and IQR (11.2% vs 12.4%). For CC, the anti-chronological registration (all deformable strategies pooled) had a slightly lower median value (0.91 vs 0.912, p < 0.001) but a better IQR (16.4% vs 21%). Conclusions The use of fD MR-LS is a good registration strategy for HN-ART as it is the best compromise in terms of median and IQR for both DSI and CC. Even though less robust in terms of CC, D MR is a good alternative. None of the time-sequence appears superior.

Hypoxia/reoxygenation induces apoptosis through a ROS-mediated caspase-8/Bid/Bax pathway in human lymphocytes

Recently, we showed that hypoxia/reoxygenation (H/R) induced apoptosis in human lymphocytes via reactive oxygen species (ROS) generation and disruption of the mitochondrial membrane; however, the signaling mechanisms responsible for these events are unclear. Here, we investigated the mechanism of H/R-induced apoptosis in human cultured lymphocytes. H/R increased the proportion of apoptotic cells, while z-IETD-fmk, z-VAD-fmk, and z-DEVD-fmk inhibited H/R-induced apoptosis. H/R also enhanced caspase-3 and caspase-8 activity. Time-sequence analysis of the induction of apoptosis by H/R revealed that H/R triggers apoptosis through a mitochondrial pathway involving caspase-8, Bid cleavage, and Bax activation. Furthermore, suppression of caspase-8 activity with z-IETD-fmk prevented Bid cleavage and Bax activation during apoptosis. N-acetylcysteine (NAC), a well-known ROS scavenger, suppressed caspase-8 activation and the subsequent cleavage of caspase-9 and caspase-3, indicating the role of ROS in caspase-8-mediated apoptosis. Overall, our results indicate that H/R induces apoptosis via a mitochondrial pathway involving caspase-8/Bid/Bax activation in human lymphocytes. Our results also suggest that ROS are critical regulators of caspase-8-mediated apoptosis in H/R-treated human lymphocytes.