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"Hernandez, Alfredo"
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Robust, real-time generic detector based on a multi-feature probabilistic method
Robust, real-time event detection from physiological signals acquired during long-term ambulatory monitoring still represents a major challenge for highly-artifacted signals. In this paper, we propose an original and generic multi-feature probabilistic detector (MFPD) and apply it to real-time QRS complex detection under noisy conditions. The MFPD method calculates a binary Bayesian probability for each derived feature and makes a centralized fusion, using the Kullback-Leibler divergence. The method is evaluated on two ECG databases: 1) the MIT-BIH arrhythmia database from Physionet containing clean ECG signals, 2) a benchmark noisy database created by adding noise recordings of the MIT-BIH noise stress test database, also from Physionet, to the MIT-BIH arrhythmia database. Results are compared with a well-known wavelet-based detector, and two recently published detectors: one based on spatiotemporal characteristic of the QRS complex and the second, as the MFDP, based on feature calculations from the University of New South Wales detector (UNSW). For both benchmark Physionet databases, the proposed MFPD method achieves the lowest standard deviation in sensitivity and positive predictivity (+P) despite its online algorithm architecture. While the statistics are comparable for low-to mildly artifactual ECG signals, the MFPD outperforms reference methods for artifacted ECG with low SNR levels reaching 87.48 ± 14.21% in sensitivity and 89.39 ± 14.67% in +P as compared to 88.30 ± 17.66% and 86.06 ± 19.67% respectively from UNSW, the best performing reference method. With demonstrations on the extensively studied QRS detection problem, we consider that the proposed generic structure of the multi-feature probabilistic detector should offer promising perspectives for long-term monitoring applications for highly-artifacted signals.
Journal Article
B2 and ALU retrotransposons are self-cleaving ribozymes whose activity is enhanced by EZH2
Transposable elements make up half of the mammalian genome. One of the most abundant is the short interspersed nuclear element (SINE). Among their million copies, B2 accounts for ∼350,000 in the mouse genome and has garnered special interest because of emerging roles in epigenetic regulation. Our recent work demonstrated that B2 RNA binds stress genes to retard transcription elongation. Although epigenetically silenced, B2s become massively up-regulated during thermal and other types of stress. Specifically, an interaction between B2 RNA and the Polycomb protein, EZH2, results in cleavage of B2 RNA, release of B2 RNA from chromatin, and activation of thermal stress genes. Although an established RNA-binding protein and histone methyltransferase, EZH2 is not known to be a nuclease. Here, we provide evidence for the surprising conclusion that B2 is a self-cleaving ribozyme. Ribozyme activity depends on Mg+2 and monovalent cations but is resistant to protease treatment. However, contact with EZH2 accelerates cleavage rate by >100-fold, suggesting that EZH2 promotes a cleavage-competent RNA conformation. B2 modification-interference analysis demonstrates that phosphorothioate changes at A and C nucleotides can substitute for EZH2. B2 nucleotides 45 to 55 and 100 to 101 are essential for activity. Finally, another family of SINEs, the human ALU element, also produces a self-cleaving RNA and is cleaved during T-cell activation as well as thermal and endoplasmic reticulum (ER) stress. Thus, B2/ALU SINEs may be classified as “epigenetic ribozymes” that function as transcriptional switches during stress. Given their high copy numbers, B2 and ALU may represent the predominant ribozyme activity in mammalian cells.
Journal Article
Apnea bradycardia detection based on new coupled hidden semi Markov model
In this paper, a method for apnea bradycardia detection in preterm infants is presented based on coupled hidden semi Markov model (CHSMM). CHSMM is a generalization of hidden Markov models (HMM) used for modeling mutual interactions among different observations of a stochastic process through using finite number of hidden states with corresponding resting time. We introduce a new set of equations for CHSMM to be integrated in a detection algorithm. The detection algorithm was evaluated on a simulated data to detect a specific dynamic and on a clinical dataset of electrocardiogram signals collected from preterm infants for early detection of apnea bradycardia episodes. For simulated data, the proposed algorithm was able to detect the desired dynamic with sensitivity of 96.67% and specificity of 98.98%. Furthermore, the method detected the apnea bradycardia episodes with 94.87% sensitivity and 96.52% specificity with mean time delay of 0.73 s. The results show that the algorithm based on CHSMM is a robust tool for monitoring of preterm infants in detecting apnea bradycardia episodes.
Journal Article
Targeting Neutrophil Adhesive Events to Address Vaso-Occlusive Crisis in Sickle Cell Patients
Neutrophils are essential to protect the host against invading pathogens but can promote disease progression in sickle cell disease (SCD) by becoming adherent to inflamed microvascular networks in peripheral tissue throughout the body. During the inflammatory response, leukocytes extravasate from the bloodstream using selectin adhesion molecules and migrate to sites of tissue insult through activation of integrins that are essential for combating pathogens. However, during vaso-occlusion associated with SCD, neutrophils are activated during tethering and rolling on selectins upregulated on activated endothelium that line blood vessels. Recently, we reported that recognition of sLe x on L-selectin by E-selectin during neutrophil rolling initiates shear force resistant catch-bonds that facilitate tethering to endothelium and activation of integrin bond clusters that anchor cells to the vessel wall. Evidence indicates that blocking this important signaling cascade prevents the congestion and ischemia in microvasculature that occurs from neutrophil capture of sickled red blood cells, which are normally deformable ellipses that flow easily through small blood vessels. Two recently completed clinical trials of therapies targeting selectins and their effect on neutrophil activation in small blood vessels reveal the importance of mechanoregulation that in health is an immune adaption facilitating rapid and proportional leukocyte adhesion, while sustaining tissue perfusion. We provide a timely perspective on the mechanism underlying vaso-occlusive crisis (VOC) with a focus on new drugs that target selectin mediated integrin adhesive bond formation.
Journal Article
Deep-sea vent phage DNA polymerase specifically initiates DNA synthesis in the absence of primers
A DNA polymerase is encoded by the deep-sea vent phage NrS-1. NrS-1 has a unique genome organization containing genes that are predicted to encode a helicase and a single-stranded DNA (ssDNA)-binding protein. The gene for an unknown protein shares weak homology with the bifunctional primase–polymerases (prim–pols) from archaeal plasmids but is missing the zinc-binding domain typically found in primases. We show that this gene product has efficient DNA polymerase activity and is processive in DNA synthesis in the presence of the NrS-1 helicase and ssDNA-binding protein. Remarkably, this NrS-1 DNA polymerase initiates DNA synthesis from a specific template DNA sequence in the absence of any primer. The de novo DNA polymerase activity resides in the N-terminal domain of the protein, whereas the C-terminal domain enhances DNA binding.
Journal Article
Recent Overview of Solar Photocatalysis and Solar Photo-Fenton Processes for Wastewater Treatment
This literature research, although not exhaustive, gives perspective to solar-driven photocatalysis, such as solar photo-Fenton and TiO2 solar photocatalysis, reported in the literature for the degradation of aqueous organic pollutants. Parameters that influence the degradation and mineralization of organics like catalyst preparation, type and load of catalyst, catalyst phase, pH, applied potential, and type of organic pollutant are addressed. Such parameters may also affect the photoactivity of the catalysts used in the studied solar processes. Solar irradiation is a renewable, abundant, and pollution-free energy source for low-cost commercial applications. Therefore, these solar processes represent an environmentally friendly alternative mainly because the use of electricity can be decreased/avoided.
Journal Article
Host population structure and species resolution reveal prophage transmission dynamics
Much knowledge about bacteriophages has been obtained via genomics and metagenomics over the last decades. However, most studies dealing with prophage diversity have rarely conducted phage species delimitation (aspect 1) and have hardly integrated the population structure of the host (aspect 2). Yet, these two aspects are essential in assessing phage diversity. Here, we implemented an operational definition of phage species (clustering at 95% identity, 90% coverage) and integrated the host’s population structure to understand prophage diversity better. Gathering the most extensive data set of Acinetobacter baumannii phages, we show that most prophage species have four or fewer prophages per species, and just five prophage species have more than 100 prophages. Most prophage species have a narrow host range and are geographically restricted; yet, very few have a broad host range being well spread in distant lineages of A. baumannii . These few broad host range prophage species are cosmopolitan and the most abundant species. Prophages in the same bacterial genome are very divergent, and prophages can easily be gained and lost within the bacterial lineages. Finally, even with this extensive data set, the prophage diversity has not been fully grasped. This study shows how integrating the host population structure and clustering at the species level allows us to better appreciate phage diversity and its transmission dynamics.
Journal Article
Parametric Analysis of an Integrated Model of Cardio-respiratory Interactions in Adults in the Context of Obstructive Sleep Apnea
An original integrated model of cardio-respiratory interactions is presented in this paper with the objective of studying the acute physiological responses evoked by obstructive sleep apnea events in adults. A comprehensive sensitivity analysis of the model is proposed during the simulation of a 20 s obstructive apnea episode using the Morris’ screening method and local sensitivity analysis. The more relevant parameters are related to the following mechanisms of the physiology: (i) the fraction of oxygen in inspired air, (ii) metabolic rates (oxygen consumption rate, CO2 production rate); (iii) chemoreflex (gains and time constants) (iv) respiratory mechanics (lung compliance and unstressed volume of air in the alveoli). These results highlight significant physiological variables that may be particularly useful for the development of novel diagnostic and therapeutic strategies, integrating a virtual patient approach.
Journal Article
Kinesthetic stimulation for obstructive sleep apnea syndrome: An “on-off” proof of concept trial
Obstructive sleep apnea (OSA) occurs when the upper airway narrows or collapses due to the loss of upper airway muscle activation at sleep onset. This study investigated the effectiveness of triggered kinesthetic stimulation in patients with OSA. This proof-of-concept, open-label, multicenter prospective study was conducted on 24 patients with severe OSA. During a one night evaluation, kinesthetic stimulation was intermittently delivered in 30 minute periods. The duration of apneas and hypopneas during
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on
and
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off
periods were compared. Five hospital-based university centers in France participated. Sleep studies were evaluated by a single scorer at a core laboratory (CHU Grenoble). Results show that during the
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on
phases, statistically significant decreases in durations of apneas and hypopneas were observed in 56% and 46% of patients, respectively. Overall, 75% of patients showed an improvement in apneas or hypopneas durations. The mean reduction in durations for patients with a significant decrease was 4.86 seconds for apneas and 6.00 seconds for hypopneas. This proof of concept study is the first to identify kinesthetic stimulation as a potentially effective therapy for OSA. These data justify evaluation in a controlled study.
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