Estimating and validating the interbeat intervals of the heart using near-infrared spectroscopy on the human forehead

In studies with near-infrared spectroscopy, the recorded signals contain information on the temporal interbeat intervals of the heart. If this cardiac information is needed exclusively and could directly be extracted, an additional electrocardiography device would be unnecessary. The aim was to estimate these intervals from signals measured with near-infrared spectroscopy with two novel approaches. In one approach, we model the heartbeat oscillations in these signals with a Fourier series where the coefficients and the fundamental frequency can continuously change over time. The time-dependent model parameters are estimated and used to calculate the interbeat intervals. The second approach uses empirical mode decomposition. The signal measured with near-infrared spectroscopy is empirically decomposed into a set of oscillatory components. The sum of a specific subset of them is an estimate of the pure heartbeat signal in which the diastolic peaks and consequential interbeat intervals are detected. We show in simultaneous electrocardiography and near-infrared spectroscopy measurements on 11 subjects (8 men and 3 woman with mean age 32.8 ± 8.1 yr), that the interbeat intervals (and the consequential pulse rate variability measures), estimated using the proposed approaches, are in high agreement with their correspondents from electrocardiography

Modelling and filtering almost periodic signals by time-varying fourier series with application to near-infrared spectroscopy

We propose a new approach to modelling almost periodic signals and to model-based estimation of such signals from noisy observations. The signal model is based on Fourier series where both the coefficients and the fundamental frequency can continuously change over time. This signal model can be represented by a factor graph which we use to derive message passing algorithms to estimate the time-dependent model parameters from the observed samples

Computational Design of Enantiocomplementary Epoxide Hydrolases for Asymmetric Synthesis of Aliphatic and Aromatic Diols

The use of enzymes in preparative biocatalysis often requires tailoring enzyme selectivity by protein engineering. Herein we explore the use of computational library design and molecular dynamics simulations to create variants of limonene epoxide hydrolase that produce enantiomeric diols from meso-epoxides. Three substrates of different sizes were targeted: cis-2,3-butene oxide, cyclopentene oxide, and cis-stilbene oxide. Most of the 28 designs tested were active and showed the predicted enantioselectivity. Excellent enantioselectivities were obtained for the bulky substrate cis-stilbene oxide, and enantiocomplementary mutants produced (S,S)- and (R,R)-stilbene diol with >97 % enantiomeric excess. An (R,R)-selective mutant was used to prepare (R,R)-stilbene diol with high enantiopurity (98 % conversion into diol, >99 % ee). Some variants displayed higher catalytic rates (kcat) than the original enzyme, but in most cases KM values increased as well. The results demonstrate the feasibility of computational design and screening to engineer enantioselective epoxide hydrolase variants with very limited laboratory screening

Multimodal recording of brain activity in term newborns during photic stimulation by near-infrared spectroscopy and electroencephalography

In this study 14 healthy term newborns (postnatal mean age 2.1 days) underwent photic stimulation during sleep on two different days. Near-infrared spectroscopy (NIRS) and electroencephalography (EEG) was acquired simultaneously. The aims of the study were: to determine (i) the sensitivity and (ii) the repeatability of NIRS to detect the hemodynamic response, (iii) the sensitivity and (iv) the repeatability of EEG to detect a visual evoked potential (VEP), (v) to analyze optical data for the optical neuronal signal, and (vi) to test whether inadequate stimulation could be reason for absent hemodynamic responses. The results of the study were as follows. (i) Sensitivity of NIRS was 61.5% to detect hemodynamic responses; (ii) their reproducibility was 41.7%. A VEP was detected (iii) in 96.3% of all subjects with (iv) a reproducibility of 92.3%. (v) In two measurements data met the criteria for an optical neuronal signal. The noise level was 9.6·10-5% change in optical density. (vi) Insufficient stimulation was excluded as reason for absent hemodynamic responses. We conclude that NIRS is an promising tool to study cognitive activation and development of the brain. For clinical application, however, the sensitivity and reproducibility on an individual level needs to be improved

Reset of inflammatory priming of joint tissue and reduction of the severity of arthritis flares by bromodomain inhibition

OBJECTIVE: We have recently shown that priming of synovial fibroblasts (SFs) drives arthritis flares. Pathogenic priming of SFs is essentially mediated by epigenetic reprogramming. Bromodomain and extra-terminal motif (BET) proteins translate epigenetic changes into transcription. Here we used a BET inhibitor to target inflammatory tissue priming and reduce flare severity in experimental arthritis. METHODS: BALB/c mice were treated intraperitoneally or locally into the paw with I-BET151, which blocks interaction of BET proteins with acetylated histones. Effect of I-BET151 on acute arthritis and/or inflammatory tissue priming was assessed in a model of repeated injections of monosodium urate crystals or zymosan into the paw. I-BET151 was given either from before arthritis induction, at peak inflammation, or after healing of the first arthritis bout. Transcriptomic (RNA-Seq), epigenomic (ATAC-Seq) and functional analysis (invasion, cytokine production, migration, senescence, metabolic flux) was performed on murine and human SFs treated with I-BET151 in vitro or in vivo. RESULTS: Systemic I-BET151 administration did not affect acute inflammation but abolished inflammatory tissue priming and diminished flare severity in both preventive and therapeutic treatment settings. I-BET151 was also effective when applied locally in the joint. BET inhibition also inhibited osteoclast differentiation, while macrophage activation in the joint was not affected. Flare reduction after BET inhibition was mediated, at least in part, by rolling back the primed transcriptional, metabolic and pathogenic phenotype of SFs. CONCLUSION: Inflammatory tissue priming is dependent on transcriptional regulation by BET proteins, which makes them promising therapeutic targets for preventing arthritis flares in previously affected joints

Analysis of slow wave oscillations in cerebral haemodynamics and metabolism following subarachnoid haemorrhage.

Aneurysmal subarachnoid haemorrhage (SAH) causes the greatest loss of productive life years of any form of stroke. Emerging concepts of pathophysiology highlight early abnormalities of microvascular function, including impaired autoregulation of cerebral blood flow and flow-metabolism coupling, as key causes of cerebral ischaemia and poor outcome. Near infrared spectroscopy (NIRS) is a non-invasive optical technique which may help identify cerebral microvascular dysfunction. The aim of this research is to investigate the status of flow-metabolism coupling by examining phase relationships between NIRS-derived concentrations of oxy-haemoglobin ([HbO2]), deoxy-haemoglobin ([HHb]) and cytochrome c oxidase oxidation ([oxCCO]). Eight sedated ventilated patients with SAH were investigated. A combined NIRS broadband and frequency domain spectroscopy system was used to measure [HbO2], [HHb] and [oxCCO] alongside other multimodal neuromonitoring. Wavelet analysis of phase relationships revealed antiphase [HbO2]-[oxCCO] and in-phase [HbO2]-[HHb] oscillations between 0.1Hz-0.01Hz consistent with compromised flow-metabolism coupling. NIRS derived variables might offer unique insights into microvascular and metabolic dysfunction following SAH, and in the future identify therapeutic windows or targets

Evaluation of the effects of a VEGFR-2 inhibitor compound on alanine aminotransferase gene expression and enzymatic activity in the rat liver

Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Time-Lapse Imaging of the Dynamics of CNS Glial-Axonal Interactions In Vitro and Ex Vivo

Myelination is an exquisite and dynamic example of heterologous cell-cell interaction, which consists of the concentric wrapping of multiple layers of oligodendrocyte membrane around neuronal axons. Understanding the mechanism by which oligodendrocytes ensheath axons may bring us closer to designing strategies to promote remyelination in demyelinating diseases. The main aim of this study was to follow glial-axonal interactions over time both in vitro and ex vivo to visualize the various stages of myelination.We took two approaches to follow myelination over time: i) time-lapse imaging of mixed CNS myelinating cultures generated from mouse spinal cord to which exogenous GFP-labelled murine cells were added, and ii) ex vivo imaging of the spinal cord of shiverer (Mbp mutant) mice, transplanted with GFP-labelled murine neurospheres. We demonstrate that oligodendrocyte-axonal interactions are dynamic events with continuous retraction and extension of oligodendroglial processes. Using cytoplasmic and membrane-GFP labelled cells to examine different components of the myelin-like sheath, we provide evidence from time-lapse fluorescence microscopy and confocal microscopy that the oligodendrocytes' cytoplasm-filled processes initially spiral around the axon in a corkscrew-like manner. This is followed subsequently by focal expansion of the corkscrew process to form short cuffs, which then extend longitudinally along the axons. We predict from this model that these spiral cuffs must extend over each other first before extending to form internodes of myelin.These experiments show the feasibility of visualizing the dynamics of glial-axonal interaction during myelination over time. Moreover, these approaches complement each other with the in vitro approach allowing visualization of an entire internodal length of myelin and the ex vivo approach validating the in vitro data