Ozone Chemistry on Greasy Glass Surfaces Affects the Levels of Volatile Organic Compounds in Indoor Environments.

The chemistry of ozone (O3) on indoor surfaces leads to secondary pollution, aggravating the air quality in indoor environments. Here, we assess the heterogeneous chemistry of gaseous O3 with glass plates after being 1 month in two different kitchens where Chinese and Western styles of cooking were applied, respectively. The uptake coefficients of O3 on the authentic glass plates were measured in the dark and under UV light irradiation typical for indoor environments (320 nm < λ < 400 nm) at different relative humidities. The gas-phase product compounds formed upon reactions of O3 with the glass plates were evaluated in real time by a proton-transfer-reaction quadrupole-interface time-of-flight mass spectrometer. We observed typical aldehydes formed by the O3 reactions with the unsaturated fatty acid constituents of cooking oils. The formation of decanal, 6-methyl-5-hepten-2-one (6-MHO), and 4-oxopentanal (4-OPA) was also observed. The employed dynamic mass balance model shows that the estimated mixing ratios of hexanal, octanal, nonanal, decanal, undecanal, 6-MHO, and 4-OPA due to O3 chemistry with authentic grime-coated kitchen glass surfaces are higher in the kitchen where Chinese food was cooked compared to that where Western food was cooked. These results show that O3 chemistry on greasy glass surfaces leads to enhanced VOC levels in indoor environments.

Spike-frequency adaptation inhibits the pairwise spike correlation.

Introduction: The spike train output correlation with pairwise neurons determines the neural population coding, which depends on the average firing rate of individual neurons. Spike frequency adaptation (SFA), which serves as an essential cellular encoding strategy, modulates the firing rates of individual neurons. However, the mechanism by which the SFA modulates the output correlation of the spike trains remains unclear. Methods: We introduce a pairwise neuron model that receives correlated inputs to generate spike trains, and the output correlation is qualified using Pearson correlation coefficient. The SFA is modeled using adaptation currents to examine its effect on the output correlation. Moreover, we use dynamic thresholds to explore the effect of SFA on output correlation. Furthermore, a simple phenomenological neuron model with a threshold-linear transfer function is utilized to confirm the effect of SFA on decreasing the output correlation. Results: The results show that the adaptation currents decreased the output correlation by reducing the firing rate of a single neuron. At the onset of a correlated input, a transient process shows a decrease in interspike intervals (ISIs), resulting in a temporary increase in the correlation. When the adaptation current is sufficiently activated, the correlation reached a steady state, and the ISIs are maintained at higher values. The enhanced adaptation current achieved by increasing the adaptation conductance further reduces the pairwise correlation. While the time and slide windows influence the correlation, they make no difference in the effect of SFA on decreasing the output correlation. Moreover, SFA simulated by dynamic thresholds also decreases the output correlation. Furthermore, the simple phenomenological neuron model with a threshold-linear transfer function confirms the effect of SFA on decreasing the output correlation. The strength of the signal input and the slope of the linear component of the transfer function, the latter of which can be decreased by SFA, could together modulate the strength of the output correlation. Stronger SFA will decrease the slope and hence decrease the output correlation. Conclusions: The results reveal that the SFA reduces the output correlation with pairwise neurons in the network by reducing the firing rate of individual neurons. This study provides a link between cellular non-linear mechanisms and network coding strategies.

Inflammasome and pyroptosis in autoimmune liver diseases.

Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

The passive properties of dendrites modulate the propagation of slowly-varying firing rate in feedforward networks.

The propagation of slowly-varying firing rates has been proved significant for the development of the central nervous system. Recent reports have shown that the membrane passive properties of dendrites play a key role in the computation of the single neuron, which is of great importance to the function of neural networks. However, it is still unclear how dendritic passive properties affect the ability of cortical networks to propagate slowly-varying spiking activity. Here, we use two-compartment biophysical models to construct multilayered feedforward neural networks (FFNs) to investigate how dendritic passive properties affect the propagation of the slow-varying inputs. In the two-compartment biophysical models, one compartment represents apical dendrites, and the other compartment describes the soma plus the axon initial segment. Area proportion occupied by somatic compartment and coupling conductance between dendritic and somatic compartments are abstracted to capture the dendritic passive properties. A time-varying signal is injected into the first layer of the FFNs and the fidelity of the signal during propagation is used to qualify the ability of the FFN to transmit wave-like signals. Numerical results reveal an optimal value of coupling conductance between dendritic and somatic compartments to maximize the fidelity of the initial spiking activity. An increase of the dendritic area enhances the initial firing rate of neurons in the first layer by increasing the response of neurons to slow-varying wave-like input, resulting in a delay of attenuation of the firing rate, thus promoting the transmission of signals in FFN. Using a mean-field approach, we examine that changes in area proportion occupied by somatic compartment and coupling conductance between dendritic and somatic compartment affect the signal propagation ability of the FFN by adjusting the input-output transform of a single neuron. With the participation of external noise, a wide range of initial firing rates maintains a unique representation during propagation, which ensures the reliable transmission of slow-varying signals in FFNs. These findings are helpful to understand how passive properties of dendrites participate in the propagation of slowly varying signals in the cerebellum.

PhenoPad: Building AI enabled note-taking interfaces for patient encounters.

Current clinical note-taking approaches cannot capture the entirety of information available from patient encounters and detract from patient-clinician interactions. By surveying healthcare providers' current note-taking practices and attitudes toward new clinical technologies, we developed a patient-centered paradigm for clinical note-taking that makes use of hybrid tablet/keyboard devices and artificial intelligence (AI) technologies. PhenoPad is an intelligent clinical note-taking interface that captures free-form notes and standard phenotypic information via a variety of modalities, including speech and natural language processing techniques, handwriting recognition, and more. The output is unobtrusively presented on mobile devices to clinicians for real-time validation and can be automatically transformed into digital formats that would be compatible with integration into electronic health record systems. Semi-structured interviews and trials in clinical settings rendered positive feedback from both clinicians and patients, demonstrating that AI-enabled clinical note-taking under our design improves ease and breadth of information captured during clinical visits without compromising patient-clinician interactions. We open source a proof-of-concept implementation that can lay the foundation for broader clinical use cases.

Automatically disambiguating medical acronyms with ontology-aware deep learning.

Modern machine learning (ML) technologies have great promise for automating diverse clinical and research workflows; however, training them requires extensive hand-labelled datasets. Disambiguating abbreviations is important for automated clinical note processing; however, broad deployment of ML for this task is restricted by the scarcity and imbalance of labeled training data. In this work we present a method that improves a model's ability to generalize through novel data augmentation techniques that utilizes information from biomedical ontologies in the form of related medical concepts, as well as global context information within the medical note. We train our model on a public dataset (MIMIC III) and test its performance on automatically generated and hand-labelled datasets from different sources (MIMIC III, CASI, i2b2). Together, these techniques boost the accuracy of abbreviation disambiguation by up to 17% on hand-labeled data, without sacrificing performance on a held-out test set from MIMIC III.

Frequency-dependent response in cortical network with periodic electrical stimulation.

Electrical stimulation can shape oscillations in brain activity. However, the mechanism of how periodic electrical stimulation modulates brain oscillations by time-delayed neural networks is poorly understood at present. To address this question, we investigate the effects of periodic stimulations on the oscillations generated via a time-delayed neural network. We specifically study the effect of unipolar and asymmetric bidirectional pulse stimulations by altering amplitude and frequency in a systematic manner. Our findings suggest that electrical stimulations play a central role in altering oscillations in the time-delayed neural network and that these alterations are strongly dependent on the stimulus frequency. We observe that the time-delayed neural network responds differently as the stimulation frequency is altered, as manifested by changes in resonance, entrainment, non-linear oscillation, or oscillation suppression. The results also indicate that the network presents similar response activities with increasing stimulus frequency under different excitation-inhibition ratios. Collectively, our findings pave the way for exploring the potential mechanism underlying the frequency-dependent modulation of network activity via electrical stimulations and provide new insights into possible electrical stimulation therapies to the neurological and psychological disorders in clinical practice.

RNA-binding protein RBM6 as a tumor suppressor gene represses the growth and progression in laryngocarcinoma.

Aberrant expression of RBM6 has been implicated in the development of human malignancies. However, the bio-function of RBM6 in laryngocarcinoma is still almost blank. Here we identified that RBM6 was downregulated in laryngocarcinoma tissues, as well as laryngocarcinoma cell lines. Notably, the expression level of RBM6 was lower in laryngocarcinoma patients at stage3/4 than that in laryngocarcinoma patients at stage1/2. Upregulation of RBM6 suppressed the proliferation of TU212 and Hep-2 cells, as shown by decreased cell viability and Ki67 level. In parallel, overexpression of RBM6 inhibited invasion and promoted apoptosis of TU212 and Hep-2 cells, as evidenced by downregulation of MMP-2 and MMP-9 protein expression and upregulation of cleaved caspase-3 protein expression. In vivo, RBM6 overexpression repressed the laryngocarcinoma tumor growth. EGFR mRNA level was higher in the laryngocarcinoma tissues than that in the adjacent normal tissues. Moreover, upregulation of RBM6 reduced the expression of EGFR, ERK and p-ERK in vitro and in vivo. Our data suggest that RBM6 as a tumor suppressor represses the growth and progression in laryngocarcinoma.

ERDS-exome: a Hybrid Approach for Copy Number Variant Detection from Whole-exome Sequencing Data.

Copy number variants (CNVs) play important roles in human disease and evolution. With the rapid development of next-generation sequencing technologies, many tools have been developed for inferring CNVs based on whole-exome sequencing (WES) data. However, as a result of the sparse distribution of exons in the genome, the limitations of the WES technique, and the nature of high-level signal noises in WES data, the efficacy of these variants remains less than desirable. Thus, there is need for the development of an effective tool to achieve a considerable power in WES CNVs discovery. In the present study, we describe a novel method, Estimation by Read Depth (RD) with Single-nucleotide variants from exome sequencing data (ERDS-exome). ERDS-exome employs a hybrid normalization approach to normalize WES data and to incorporate RD and single-nucleotide variation information together as a hybrid signal into a paired hidden Markov model to infer CNVs from WES data. Based on systematic evaluations of real data from the 1000 Genomes Project using other state-of-the-art tools, we observed that ERDS-exome demonstrates higher sensitivity and provides comparable or even better specificity than other tools. ERDS-exome is publicly available at: https://erds-exome.github.io.

Extending gene ontology with gene association networks.

MOTIVATION: Gene ontology (GO) is a widely used resource to describe the attributes for gene products. However, automatic GO maintenance remains to be difficult because of the complex logical reasoning and the need of biological knowledge that are not explicitly represented in the GO. The existing studies either construct whole GO based on network data or only infer the relations between existing GO terms. None is purposed to add new terms automatically to the existing GO. RESULTS: We proposed a new algorithm 'GOExtender' to efficiently identify all the connected gene pairs labeled by the same parent GO terms. GOExtender is used to predict new GO terms with biological network data, and connect them to the existing GO. Evaluation tests on biological process and cellular component categories of different GO releases showed that GOExtender can extend new GO terms automatically based on the biological network. Furthermore, we applied GOExtender to the recent release of GO and discovered new GO terms with strong support from literature. AVAILABILITY AND IMPLEMENTATION: Software and supplementary document are available at www.msu.edu/%7Ejinchen/GOExtender CONTACT: jinchen@msu.edu or ydwang@hit.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Analysis of correlated factors of cervical lymphatic metastasis of T3 and T4 glottic carcinoma].

OBJECTIVE: To analyze the correlated factors of cervical lymphatic metastasis of T3 and T4 glottic carcinoma. METHOD: We did a retrospective analysis of 91 glottic carcinoma patients' clinical data to analyze cervical lymph node metastasis on different T stage, pathologic degree and the tumor sites. RESULT: The cervical lymph node metastasis rate of 91 cases of T3 and T4 glottic carcinoma was 21.98%. T3 group's metastasis rate was 18.06% (13/72), T4 group's metastasis rate was 36.84% (7/19), P > 0.05. Grouped according to the degree of pathological differentiation, well-differentiated squamous cell carcinoma metastasis rate is 13.89% (5/36), middle-differentiated squamous cell carcinoma metastasis rate is 26.00% (13/50), and poorly-differentiated squamous cell carcinoma metastasis rate is 40.00% (2/5), P > 0.05. Cervical lymph node metastasis rate was 16.22%, when the tumor invading supraglottic region. Cervical lymph node metastasis rate was 15.38%, when the tumor invading subraglottic region. Cervical lymph node metastasis rate was 46.15%, when the tumor invading supraglottic and subraglottic region (P < 0.01). CONCLUSION: Cervical lymph node metastasis in cN0 patient with supraglottic carcinoma is effected by T classification, cervical lymphatic metastasis of T3 and T4 glottic carcinoma is not entirely effected by T stage and pathologic degree. When the tumor invades supraglottic and subraglottic region, cervical lymph node metastasis is significantly higher. Therefore, the area of tumor invasion is an important factor for lymph node metastasis.

[The related factors analysis of difficult laryngeal exposure under retaining laryngoscope].

OBJECTIVE: To analyze the related factors of difficult laryngeal exposure under retaining laryngoscope. METHOD: We did a retrospective analysis of 287 retaining laryngoscope surgery patients' clinical datas to observe the relationship between difficult glottis exposure and patients' gender, degree of mouth opening, BMI, neck circumference, head and neck flexion, TMD, HMD and SMD. RESULT: By ROC curve analysis, we determine the optimal threshold for TMD was 7.35 cm, HMD was 6.33 cm, SMD was 14.75 cm. Univariate analysis showed that gender, and glottis exposure had no significant correlation with difficult laryngeal exposure under retaining laryngoscope. Degree of mouth opening, BMI, neck circumference, head and neck flexion, TMD, HMD and SMD had correlation with difficult laryngeal exposure. Multivariate analysis showed that neck circumference, head and neck flexion, TMD, SMD were independent factors of difficult laryngeal exposure under retaining laryngoscope. CONCLUSION: Measurement of neck circumference, head and neck flexion, TMD, SMD before the operation is important for the prediction of difficult laryngeal exposure under retaining laryngoscope.

Analyzing large-scale samples confirms the association between the rs1051730 polymorphism and lung cancer susceptibility.

The early genome-wide association studies (GWAS) found a significant association between lung cancer and rs1051730 (15q25) polymorphism. However, the subsequent studies reported consistent and inconsistent results in different populations. Three meta-analysis studies were thus performed to reevaluate the association. But their results remain inconsistent. After that, some new GWAS studies reported conflicting results again. We think that the divergence of these results may be due to small-scale samples or heterogeneity among different populations. Therefore, we reevaluated the association by collecting more samples (N = 33,617 cases and 116,639 controls) from 31 studies, which incorporate 8 new studies and 23 previous studies used by one or more of the three meta-analysis studies. We observed a significant association between lung cancer and rs1051730 in pooled population by using allele (OR = 1.30, 95% CI = 1.27-1.34, P < 0.0001), dominant (OR = 1.41, 95% CI = 1.29-1.55, P < 0.0001), recessive (OR = 1.53, 95% CI = 1.42-1.65, P < 0.0001) and additive (OR = 1.75, 95% CI = 1.61-1.90, P < 0.0001) models. Through the subgroup analysis, we observed a significant heterogeneity only in East Asian population (P = 0.006, I(2) = 66.9%), and the association is significant in all subgroups (OR = 1.2976, 95% CI = 1.2622-1.3339 (European ancestry), OR = 1.5025, 95% CI = 1.2465-1.8110 (African), OR = 1.7818, 95% CI = 1.3915-2.2815 (East Asian), P < 0.0001). We believe that these results will contribute to understanding the genetic mechanism of lung cancer.

LncRNA2Function: a comprehensive resource for functional investigation of human lncRNAs based on RNA-seq data.

BACKGROUND: The GENCODE project has collected over 10,000 human long non-coding RNA (lncRNA) genes. However, the vast majority of them remain to be functionally characterized. Computational investigation of potential functions of human lncRNA genes is helpful to guide further experimental studies on lncRNAs. RESULTS: In this study, based on expression correlation between lncRNAs and protein-coding genes across 19 human normal tissues, we used the hypergeometric test to functionally annotate a single lncRNA or a set of lncRNAs with significantly enriched functional terms among the protein-coding genes that are significantly co-expressed with the lncRNA(s). The functional terms include all nodes in the Gene Ontology (GO) and 4,380 human biological pathways collected from 12 pathway databases. We successfully mapped 9,625 human lncRNA genes to GO terms and biological pathways, and then developed the first ontology-driven user-friendly web interface named lncRNA2Function, which enables researchers to browse the lncRNAs associated with a specific functional term, the functional terms associated with a specific lncRNA, or to assign functional terms to a set of human lncRNA genes, such as a cluster of co-expressed lncRNAs. The lncRNA2Function is freely available at http://mlg.hit.edu.cn/lncrna2function. CONCLUSIONS: The LncRNA2Function is an important resource for further investigating the functions of a single human lncRNA, or functionally annotating a set of human lncRNAs of interest.

LncRNA2Target: a database for differentially expressed genes after lncRNA knockdown or overexpression.

Long non-coding RNAs (lncRNAs) have emerged as critical regulators of genes at epigenetic, transcriptional and post-transcriptional levels, yet what genes are regulated by a specific lncRNA remains to be characterized. To assess the effects of the lncRNA on gene expression, an increasing number of researchers profiled the genome-wide or individual gene expression level change after knocking down or overexpressing the lncRNA. Herein, we describe a curated database named LncRNA2Target, which stores lncRNA-to-target genes and is publicly accessible at http://www.lncrna2target.org. A gene was considered as a target of a lncRNA if it is differentially expressed after the lncRNA knockdown or overexpression. LncRNA2Target provides a web interface through which its users can search for the targets of a particular lncRNA or for the lncRNAs that target a particular gene. Both search types are performed either by browsing a provided catalog of lncRNA names or by inserting lncRNA/target gene IDs/names in a search box.

TF2LncRNA: identifying common transcription factors for a list of lncRNA genes from ChIP-Seq data.

High-throughput genomic technologies like lncRNA microarray and RNA-Seq often generate a set of lncRNAs of interest, yet little is known about the transcriptional regulation of the set of lncRNA genes. Here, based on ChIP-Seq peak lists of transcription factors (TFs) from ENCODE and annotated human lncRNAs from GENCODE, we developed a web-based interface titled "TF2lncRNA," where TF peaks from each ChIP-Seq experiment are crossed with the genomic coordinates of a set of input lncRNAs, to identify which TFs present a statistically significant number of binding sites (peaks) within the regulatory region of the input lncRNA genes. The input can be a set of coexpressed lncRNA genes or any other cluster of lncRNA genes. Users can thus infer which TFs are likely to be common transcription regulators of the set of lncRNAs. In addition, users can retrieve all lncRNAs potentially regulated by a specific TF in a specific cell line of interest or retrieve all TFs that have one or more binding sites in the regulatory region of a given lncRNA in the specific cell line. TF2LncRNA is an efficient and easy-to-use web-based tool.

Impacts of nitrate and nitrite on physiology of Shewanella oneidensis.

Shewanella oneidensis exhibits a remarkable versatility in anaerobic respiration, which largely relies on its diverse respiratory pathways. Some of these are expressed in response to the existence of their corresponding electron acceptors (EAs) under aerobic conditions. However, little is known about respiration and the impact of non-oxygen EAs on the physiology of the microorganism when oxygen is present. Here we undertook a study to elucidate the basis for nitrate and nitrite inhibition of growth under aerobic conditions. We discovered that nitrate in the form of NaNO3 exerts its inhibitory effects as a precursor to nitrite at low concentrations and as an osmotic-stress provider (Na(+)) at high concentrations. In contrast, nitrite is extremely toxic, with 25 mM abolishing growth completely. We subsequently found that oxygen represses utilization of all EAs but nitrate. To order to utilize EAs with less positive redox potential, such as nitrite and fumarate, S. oneidensis must enter the stationary phase, when oxygen respiration becomes unfavorable. In addition, we demonstrated that during aerobic respiration the cytochrome bd oxidase confers S. oneidensis resistance to nitrite, which likely functions via nitric oxide (NO).

Crp-dependent cytochrome bd oxidase confers nitrite resistance to Shewanella oneidensis.

Shewanella oneidensis is able to respire on a variety of organic and inorganic substrates, including nitrate and nitrite. Conversion of nitrate to nitrite and nitrite to ammonium is catalysed by periplasmic nitrate and nitrite reductases (NAP and NRF) respectively. Global regulator Crp (cyclic AMP receptor protein) is essential for growth of S. oneidensis on both nitrate and nitrite. In this study, we discovered that crp mutants are not only severely deficient in nitrate or nitrite respiration, but are also hypersensitive to nitrite. This hypersusceptibility phenotype is independent of nitrite respiration. Using random transposon mutagenesis, we obtained 73 Δcrp suppressor strains resistant to nitrite. Transposon insertion sites in 24 suppressor strains were exclusively mapped in the region upstream of the cyd operon encoding a cytochrome bd oxidase, resulting in expression of the operon now driven by a Crp-independent promoter. Further investigation indicated that the promoter in suppressor strains comes from the transposon. Mutational analysis of the cydB gene (encoding the essential subunit II of the bd oxidase) confirmed that the cytochrome bd oxidase confers nitrite resistance to S. oneidensis.

A Crp-dependent two-component system regulates nitrate and nitrite respiration in Shewanella oneidensis.

We have previously illustrated the nitrate/nitrite respiratory pathway of Shewanella oneidensis, which is renowned for its remarkable versatility in respiration. Here we investigated the systems regulating the pathway with a reliable approach which enables characterization of mutants impaired in nitrate/nitrite respiration by guaranteeing biomass. The S. oneidensis genome encodes an Escherichia coli NarQ/NarX homolog SO3981 and two E. coli NarP/NarL homologs SO1860 and SO3982. Results of physiological characterization and mutational analyses demonstrated that S. oneidensis possesses a single two-component system (TCS) for regulation of nitrate/nitrite respiration, consisting of the sensor kinase SO3981(NarQ) and the response regulator SO3982(NarP). The TCS directly controls the transcription of nap and nrfA (genes encoding nitrate and nitrite reductases, respectively) but regulates the former less tightly than the latter. Additionally, phosphorylation at residue 57 of SO3982 is essential for its DNA-binding capacity. At the global control level, Crp is found to regulate expression of narQP as well as nap and nrfA. In contrast to NarP-NarQ, Crp is more essential for nap rather than nrfA.

Genetic and molecular characterization of flagellar assembly in Shewanella oneidensis.

Shewanella oneidensis is a highly motile organism by virtue of a polar flagellum. Unlike most flagellated bacteria, it contains only one major chromosome segment encoding the components of the flagellum with the exception of the motor proteins. In this region, three genes encode flagellinsaccording to the original genome annotation. However, we find that only flaA and flaB encode functional filament subunits. Although these two genesare under the control of different promoters, they are actively transcribed and subsequently translated, producing a considerable number of flagellin proteins. Additionally, both flagellins are able to interact with their chaperon FliS and are subjected to feedback regulation. Furthermore, FlaA and FlaB are glycosylated by a pathwayinvolving a major glycosylating enzyme,PseB, in spite of the lack of the majority of theconsensus glycosylation sites. In conclusion, flagellar assembly in S. oneidensis has novel features despite the conservation of homologous genes across taxa.