A Comparative Study of Causality Detection Methods in Root Cause Diagnosis: From Industrial Processes to Brain Networks.

Abstracting causal knowledge from process measurements has become an appealing topic for decades, especially for fault root cause analysis (RCA) based on signals recorded by multiple sensors in a complex system. Although many causality detection methods have been developed and applied in different fields, some research communities may have an idiosyncratic implementation of their preferred methods, with limited accessibility to the wider community. Targeting interested experimental researchers and engineers, this paper provides a comprehensive comparison of data-based causality detection methods in root cause diagnosis across two distinct domains. We provide a possible taxonomy of those methods followed by descriptions of the main motivations of those concepts. Of the two cases we investigated, one is a root cause diagnosis of plant-wide oscillations in an industrial process, while the other is the localization of the epileptogenic focus in a human brain network where the connectivity pattern is transient and even more complex. Considering the differences in various causality detection methods, we designed several sets of experiments so that for each case, a total of 11 methods could be appropriately compared under a unified and reasonable evaluation framework. In each case, these methods were implemented separately and in a standard way to infer causal interactions among multiple variables to thus establish the causal network for RCA. From the cross-domain investigation, several findings are presented along with insights into them, including an interpretative pitfall that warrants caution.

Latent Prototype-Based Clustering: A Novel Exploratory Electroencephalography Analysis Approach.

Electroencephalography (EEG)-based applications in brain-computer interfaces (BCIs), neurological disease diagnosis, rehabilitation, etc., rely on supervised approaches such as classification that requires given labels. However, with the ever-increasing amount of EEG data, incomplete or incorrectly labeled or unlabeled EEG data are increasing. It likely degrades the performance of supervised approaches. In this work, we put forward a novel unsupervised exploratory EEG analysis solution by clustering based on low-dimensional prototypes in latent space that are associated with the respective clusters. Having the prototype as a baseline of each cluster, a compositive similarity is defined to act as the critic function in clustering, which incorporates similarities on three levels. The approach is implemented with a Generative Adversarial Network (GAN), termed W-SLOGAN, by extending the Stein Latent Optimization for GANs (SLOGAN). The Gaussian Mixture Model (GMM) is utilized as the latent distribution to adapt to the diversity of EEG signal patterns. The W-SLOGAN ensures that images generated from each Gaussian component belong to the associated cluster. The adaptively learned Gaussian mixing coefficients make the model remain effective in dealing with an imbalanced dataset. By applying the proposed approach to two public EEG or intracranial EEG (iEEG) epilepsy datasets, our experiments demonstrate that the clustering results are close to the classification of the data. Moreover, we present several findings that were discovered by intra-class clustering and cross-analysis of clustering and classification. They show that the approach is attractive in practice in the diagnosis of the epileptic subtype, multiple labelling of EEG data, etc.

Antiviral Effect of Extracellular Matrix Protein ABI3BP on Vesicular Stomatitis Virus and Its Mechanism: A Preliminary Study In Vitro.

Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein (ABI3BP) on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway.Methods The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels.Results The VSV-GFP-infected BJ-5ta cell model was successfully established. Efficient knockdown of ABI3BP in BJ-5ta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 - 3.5 times (P<0.01) and 2.2 - 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection.Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication, and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.

Effects of Yinchenhao decoction on self-regulation of renin-angiotensin system by targeting angiotensin converting enzyme 2 in bile duct-ligated rat liver.

In order to investigate whether Yinchenhao decoction (YCHD) attenuates hepatic fibrogenesis in the bile duct ligation (BDL) model via recovering and restoring the self-regulation and balance of the renin-angiotensin system (RAS), 33 specific-pathogen-free (SPF) male Sprague-Dawley rats with common BDL and scission were randomly divided into five groups as follows: G1, the sham group (n=4); G2, BDL 7-day group (n=5); G3, BDL+YCHD 430 mg/mL (n=8); G4, BDL+losartan 0.65 mg/mL (ARB group, n=8); G5, model group (BDL without any treatment, n=8). YCHD and losartan (10 mL·kg(-1)·day(-1)) were given by gastric gavage for 16 days following BDL in G3 and G4 groups, respectively. The effect of YCHD on liver fibrosis and the detailed molecular mechanisms were assessed by liver function including total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IDBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Histological changes were observed by transmission electron microscopy (TEM) and Masson trichrome staining. Western blotting was used to detect the protein expression level of the renin-angiotensin system (RAS) components including angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R), ACE2, angiotensin II (AngII) as well as transforming growth factor ß1 (TGFß1). The experimental data were analyzed by principle component analytical method of pattern recognition. The results showed that biochemically, serum TBIL, DBIL, IDBIL, ALT and AST levels were markedly increased following BDL as compared with the sham group (P<0.05). Serum TBIL, IDBIL and DBIL levels in G3 group were dramatically decreased as compared with G5 and G4 groups (P<0.05). Serum AST level in G3 was significantly lowered than in G5 group (P<0.05), but there was no significant difference in ALT among G3, G4 and G5 groups (P>0.05). Histologically, livers in G3 group showed less hepatocytes necrosis, less bile duct hyperplasia and less collagen formation than in G4 and G5 groups. The protein expression levels of ACE2, ACE, AngII, AT1R and TGFß1 in G2, G3 and G4 groups were significantly higher than in sham group (P<0.05), and lower than in G5 group (P<0.05). However, the differences among G2, G3 and G4 groups were not significant (P>0.05). ACE2 protein expression in G3 group was significantly higher than in G2 group (P<0.05) and there was no significant difference in comparison with G4 group (P>0.05). Moreover, the protein expression of TGFß1 in G3 group was significantly lower than in G5 and G4 groups (P<0.05). Our findings suggest that the antifibrotic effects of YCHD may be associated with the decreased classical RAS pathway components and TGFß1 downexpression so as to recover and rebuild self-regulation of the RAS by elevating the protein expression of ACE2.

[SCN5A mutation in patients with Brugada electrocardiographic pattern induced by fever].

OBJECTIVE: To explore the relationship between SCN5A, SCN1b, SCN3b and GPD1L genotypes and the risk of malignant arrhythmia in patients with Brugada electrocardiographic pattern induced by fever. METHODS: The clinical data and peripheral blood of patients with Brugada electrocardiographic pattern induced by fever were collected. Patients with depolarization abnormality associated with hypertension, coronary heart disease, drugs and other factors were excluded. The direct DNA sequencing was used to screen the mutation of candidate gene SCN5A, SCN1b, SCN3b and GPD1L. If gene variation was found, mutation or polymorphism was then determined by comparison with 200 control individuals. The relationship between genotype and phenotype as well as the risk of malignant arrhythmia were analyzed. RESULTS: Five eligible patients with fever-induced Brugada ECG pattern were included in this study. TypeI Brugada ECG was presented in all five patients in fibrile state and disappeared in normothermia. No sudden cardiac death (SCD) occurred and no ventricular arrhythmia was presented in Holter monitor during the 3 to 5 years follow-up period. Six gene variants were found including a novel missense mutation of base C to T, named Arg965 Cys (R965C), which located in 965 codon of the 17 exon in SCN5A, and five SCN5A polymorphisms including A29A (c.87A>G), R1193Q (c.3578G>A), D1819D (c.5457T>C), exon11 -24G>A, exon23 +4A>G. CONCLUSION: SCN5A mutation is related to fever-induced Brugada ECG pattern. However, individuals with Brugada ECG pattern induced by fever bear low risk of malignant arrhythmia and SCD during fibrile state and follow up in this small patient cohort.

Pattern analysis approach reveals restriction enzyme cutting abnormalities and other cDNA library construction artifacts using raw EST data.

BACKGROUND: Expressed Sequence Tag (EST) sequences are widely used in applications such as genome annotation, gene discovery and gene expression studies. However, some of GenBank dbEST sequences have proven to be "unclean". Identification of cDNA termini/ends and their structures in raw ESTs not only facilitates data quality control and accurate delineation of transcription ends, but also furthers our understanding of the potential sources of data abnormalities/errors present in the wet-lab procedures for cDNA library construction. RESULTS: After analyzing a total of 309,976 raw Pinus taeda ESTs, we uncovered many distinct variations of cDNA termini, some of which prove to be good indicators of wet-lab artifacts, and characterized each raw EST by its cDNA terminus structure patterns. In contrast to the expected patterns, many ESTs displayed complex and/or abnormal patterns that represent potential wet-lab errors such as: a failure of one or both of the restriction enzymes to cut the plasmid vector; a failure of the restriction enzymes to cut the vector at the correct positions; the insertion of two cDNA inserts into a single vector; the insertion of multiple and/or concatenated adapters/linkers; the presence of 3'-end terminal structures in designated 5'-end sequences or vice versa; and so on. With a close examination of these artifacts, many problematic ESTs that have been deposited into public databases by conventional bioinformatics pipelines or tools could be cleaned or filtered by our methodology. We developed a software tool for Abnormality Filtering and Sequence Trimming for ESTs (AFST, http://code.google.com/p/afst/) using a pattern analysis approach. To compare AFST with other pipelines that submitted ESTs into dbEST, we reprocessed 230,783 Pinus taeda and 38,709 Arachis hypogaea GenBank ESTs. We found 7.4% of Pinus taeda and 29.2% of Arachis hypogaea GenBank ESTs are "unclean" or abnormal, all of which could be cleaned or filtered by AFST. CONCLUSIONS: cDNA terminal pattern analysis, as implemented in the AFST software tool, can be utilized to reveal wet-lab errors such as restriction enzyme cutting abnormities and chimeric EST sequences, detect various data abnormalities embedded in existing Sanger EST datasets, improve the accuracy of identifying and extracting bona fide cDNA inserts from raw ESTs, and therefore greatly benefit downstream EST-based applications.

[Diagnostic value of serum angiopoietin-2 level in pancreatic cancer].

OBJECTIVE: To evaluate the diagnostic value of serum angiopoietin-2 (Ang-2) level in pancreatic cancer patients. METHODS: Serum Ang-2 level was measured by enzyme-linked immunosorbent assays (ELISA) in samples from 116 patients with pancreatic cancer, 50 patients with chronic pancreatitis, and 50 normal control subjects. RESULTS: The serum Ang-2 level in patients with pancreatic cancer [(1539.0 ± 449.3) ng/L] was significantly higher than those in patients with pancreatitis [(1044.6 ± 246.1) ng/L, P < 0.01] and normal control subjects [(1075.6 ± 228.2) ng/L, P < 0.01]. There was no significant difference of serum Ang-2 levels between patients with pancreatitis and normal controls. Pancreatic caner patients with lymph node metastasis had a significantly higher serum Ang-2 level [(1890.1 ± 354.9) ng/L] than those without metastasis [(1212.1 ± 224.2) ng/L, P < 0.01]. The area under ROC curve of serum Ang-2 level for diagnosis of pancreatic cancer was 0.819. CONCLUSION: The serum Ang-2 level can be a useful indicator for diagnosis of pancreatic cancer.

[Effects of antidiabetic drug metformin on human breast carcinoma cells with different estrogen receptor expressing in vitro].

AIM: To research different effects of human breast carcinoma cells with different estrogen receptor expressing by antidiabetic drug metformin, and preliminary explore the possible underlying molecular mechanisms. METHODS: Cells were treated with metformin. Growth inhibition rates of the cells were measured by MTT assay. Cell cycle and apoptosis were detected by flow cytometery (FCM). Expressions of HIF-1α mRNA in the cells were measured by RT-PCR. RESULTS: After drug intervention, the cell proliferation were inhibited by metformin, and reinforced with the concentration and reaction time increase (P<0.05). The growth inhibition rates of MCF-7(ER(+);) breast carcinoma cell were higher than MDA-MB-231(ER(-);) breast carcinoma cell at each concentration group (P<0.05). The results of FCM prompted: MCF-7(ER(+);) breast carcinoma cell was arrested in G1 phase by metformin significantly in a dose-dependent increase(P<0.05). While for MDA-MB-231(ER(-);) breast carcinoma cell, only the 20 and 40 mmol/L groups had significant difference compared with the control group(P<0.05); and the percentage of G1 phase arresting were lower than MCF-7(ER(+);) breast carcinoma cell at the same concentration group(P<0.05). The effect of apoptosis for these two kinds of cells via metformin were not obvious(P<0.05). The expressions of HIF-1α mRNA detected by RT-PCR prompted: the expressions of HIF-1α mRNA for these two breast carcinoma cells were in a dose-dependent decrease(P<0.05). CONCLUSION: The effect of metformin for human breast carcinoma cell with estrogen receptor was better than the one without estrogen receptor. Maybe the molecular mechanism had a relationship with HIF-1α up-regulating.

The MRL mouse heart does not recover ventricular function after a myocardial infarction.

INTRODUCTION: Murphy Roth Large (MRL) mice have a remarkable regenerative capacity. A recent report demonstrated rapid cardiac healing in these mice following cryogenically induced right ventricular injury, suggesting the potential for new regenerative therapies to restore cardiac function in mammals. We therefore evaluated the cardiac regenerative wound-healing response and functional recovery of MRL mice in response to a clinically relevant left ventricular coronary ligation. METHODS: Female MRL/MpJ+/+ and C57BL/6 mice underwent left coronary artery ligation. Cardiac function was evaluated by echocardiography at Days 0, 5, 15, and 60. At Day 96, invasive hemodynamics were assessed by pressure-volume loops using a Millar catheter. Hearts were perfusion fixed for histomorphometric analysis at Days 5, 15, and 96. Some hearts were fresh frozen at Days 5 and 15 for immunohistochemical analysis and digital quantitation of blood vessel density (CD31) and cellular proliferation (Ki67). RESULTS: MRL mice healed ear punch wounds (89% reduction in area) more extensively than C57BL/6 mice (28% reduction in area) but did not differ functionally from C57BL/6 animals before or after coronary ligation. In addition, blood vessel density and cell proliferation were similar between the two strains. CONCLUSIONS: Although MRL mice rapidly healed ear injury, they did not exhibit regeneration of the left ventricle or enhanced functional improvement in response to coronary ligation. The prospect of cardiac regeneration after myocardial infarction will require further studies designed to elucidate the possible mechanisms of functional restoration.

A physico-chemical study of triple helix formation by an oligodeoxythymidylate with N3'--> P5' phosphoramidate linkages.

Non-denaturing gel retardation assay, DNA melting experiments and FTIR spectroscopy were used to characterize the triple helix formed by a 15mer 2'-deoxythymidylate with N3'-->P5'phosphoramidate linkages with its target sequence. The results indicate that: (i) the pentadecadeoxythymidylate with phosphoramidate linkages [dT15(np)] is highly potent to form a triple helix with a dT15*dA15target duplex through Hoogsteenbase-pairing; (ii) it forms a dT15(np)*dA15xdT15(np) triplex with the single-stranded oligo-2'-deoxyadenylate (dA15) without detectable double-helical intermediate; (iii) it does not only form a triple helix on the dT15*dA15target duplex, but also partially displaces the dT15 strand from the dT15*dA15duplex to form a dT15(np)*dA15xdT15(np) complex.