Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts

AbstractBackgroundWhen the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of-eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront.MethodA quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified.ResultsFor an appropriately placed stimulus, in accord with model predictions: 1. The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.8±5.7mm). 2. The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. 3. The mean coupling interval was 164.6±11.0ms during premature stimulation and 190.7±20.4ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature and functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges.DiscussionReentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double-loop reentrant circuit pattern is a consequence of wavefront bifurcation around this UBL followed by coalescence, and then impulse propagation through the isthmus. The wavefront is blocked from propagating laterally away from the isthmus by sharp increases in border zone thickness, which results in critically convex wavefront curvature at VT cycle lengths

Analysis of the Genome Sequence of the Medicinal Plant Salvia miltiorrhiza

Salvia miltiorrhiza Bunge (Danshen) is a medicinal plant of the Lamiaceae family, and its dried roots have long been used in traditional Chinese medicine with hydrophilic phenolic acids and tanshinones as pharmaceutically active components (Xu et al., 2016; Zhang et al., 2014). The first step of tanshinone biosynthesis is the bicyclization of the general diterpene precursor (E, E, E)-geranylgeranyl diphosphate (GGPP) to copalyl diphosphate (CPP) by CPP synthases (CPSs), which is followed by cyclization or rearrangement reaction catalyzed by kaurene synthase-like enzymes (KSL). The resulting intermediate is usually an olefin, which requires the insertion of oxygen by cytochrome P450 mono-oxygenases (CYPs) for the final production of diterpenoids (Zi et al., 2014). While the CPS, KSL and several early acting CYPs (CYP76AH1, CYP76AH3 and CYP76AK1) for tanshinone biosynthesis have been identified in S. miltiorrhiza (Gao et al., 2009; Guo et al., in press; Guo et al., 2013; Zi and Peters, 2013), the majority of the overall biosynthetic pathway, as well as the relevant regulatory factors associated with tanshinone production, remains elusive (Figure 1B)

LocoMuJoCo: A Comprehensive Imitation Learning Benchmark for Locomotion

Imitation Learning (IL) holds great promise for enabling agile locomotion in embodied agents. However, many existing locomotion benchmarks primarily focus on simplified toy tasks, often failing to capture the complexity of real-world scenarios and steering research toward unrealistic domains. To advance research in IL for locomotion, we present a novel benchmark designed to facilitate rigorous evaluation and comparison of IL algorithms. This benchmark encompasses a diverse set of environments, including quadrupeds, bipeds, and musculoskeletal human models, each accompanied by comprehensive datasets, such as real noisy motion capture data, ground truth expert data, and ground truth sub-optimal data, enabling evaluation across a spectrum of difficulty levels. To increase the robustness of learned agents, we provide an easy interface for dynamics randomization and offer a wide range of partially observable tasks to train agents across different embodiments. Finally, we provide handcrafted metrics for each task and ship our benchmark with state-of-the-art baseline algorithms to ease evaluation and enable fast benchmarking.Comment: https://github.com/robfiras/loco-mujoc

The calibration of photographic and spectroscopic films: The response of 2aO film to small dosages of alpha particles from 3/10th's rad to 8 rads at energy levels 153 MeV, 79 MeV and 47 MeV

The 2aO film, pre-exposed to a series of neutral density filters which on development under standard conditions will produce the standard H-D curve for that film, were then exposed to Alpha paricles with a dose range of 3/10ths rads to 8 rads while varying the energy of the particles using 153 MeV, 70 MeV, and 47 MeV, respectively. An analysis of the film shows that the 3/10th rad dose produces the lowest optical density changes at 70 MeV and 47 MeV. While the optical density readings for the darker patterns seem to oscillate and decrease when exposed to radiation dosages of 3/10th rads to 8 rads

Size-dependent Auger spectra and two-hole Coulomb interaction of small supported Cu-clusters

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Auger (L3M4,5M4,5) and X-ray photoionization spectra (2p, 3d) of mass-selected CuN-clusters supported by a thin natural silica layer are presented in the size range N = 8–55 atoms per cluster. The Auger spectra of all clusters are shifted to a lower kinetic energy with respect to the spectrum of the bulk. Furthermore the Auger energy decreases systematically with decreasing cluster size. The binding energies of the 2p and 3d valence states are higher than the corresponding bulk values. Using the energy of the Auger main line, the corresponding core hole peak and the centroid of the self-convoluted 3d valence band the on-site Coulomb interaction energy Udd of the two-hole final state as a function of cluster size has been determined

Prospective Cohort Study of Patients With Neck Pain in a Manual Therapy Setting: Design and Baseline Measures.

OBJECTIVES:The purpose of this study was to describe the design and baseline measurements of a prospective multicenter cohort study in patients with neck pain treated by Dutch manual therapists. Objectives of the study were to determine which patients seek help from a manual therapist, to describe usual care manual therapy in patients with neck pain, to examine the occurrence of nonserious adverse events after treatment, to describe predictors of adverse events, and to determine whether the occurrence of nonserious adverse events affect outcome after manual therapy care. METHODS:During a 3-month inclusion period, consecutive patients aged between 18 and 80 years presenting with neck pain in manual therapy practices in The Netherlands were included in the study. Baseline questionnaires included the Numeric Rating Scale, Neck Disability Index (NDI), Neck Bournemouth Questionnaire, Fear Avoidance Beliefs Questionnaire (FABQ), and Patient Expectancy List. Within the treatment episode, manual therapist clinical reasoning and applied interventions were registered and patients reported on adverse events. At the end of the treatment episode and at 12-month follow-up, pain intensity (Numeric Rating Scale), functional outcomes (NDI, Neck Bournemouth Questionnaire), personal factors (FABQ), and global perceived effect were measured. RESULTS:During the 3-month inclusion period, 263 participating manual therapists collected data on 1193 patients with neck pain. Most patients (69.4%) were female. The mean age was 44.7 (±13.7) years. The NDI showed overall mild disability (mean score 26%). Mean scores in pain intensity were moderate (4.8), and there was low risk of prolonged disability owing to personal factors (FABQ). CONCLUSION:This study provides information on baseline characteristics of patients visiting manual therapists for neck pain. In The Netherlands, patients seeking care of manual therapists are comparable to patients in other countries regarding demographics and neck pain characteristics

Observational cohort study of rilpivirine (RPV) utilization in Europe

INTRODUCTION Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce. METHODS Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann-Whitney U test and Chi-square test. A logistic regression model was used to compare participants' characteristics by treatment group. Kaplan-Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL). RESULTS 1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3-5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001). CONCLUSION Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS)

Photografted methacrylate-based monolithic columns coated with cellulose tris(3,5-dimethylphenylcarbamate) for chiral separation in CEC

A chiral capillary monolithic column for enantiomer separation in capillary electrochromatography was prepared by coating cellulose tris(3,5-dimethylphenylcarbamate) on porous glycidyl methacrylate-co-ethylene dimethacrylate monolith in capillary format grafted with chains of [2(methacryloyloxy)ethyl] trimethylammonium chloride. The surface modification of the monolith by the photografting of [2(methacryloyloxy)ethyl] trimethylammonium chloride monomer as well as the coating conditions of cellulose tris(3,5-dimethylphenylcarbamate) onto the grafted monolithic scaffold were optimized to obtain a stable and reproducible chiral stationary phase for capillary electrochromatography. The effect of organic modifier (acetonitrile) in aqueous mobile phase for the enantiomer separation by capillary electrochromatography was also investigated. Several pairs of enantiomers including acidic, neutral, and basic analytes were tested and most of them were partially or completely resolved under aqueous mobile phases. The prepared monolithic chiral stationary phases exhibited a good stability, repeatability, and column-to-column reproducibility, with relative standard deviations below 11% in the studied electrochromatographic parameters.Fil: Echevarria, Romina Noel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Carrasco Correa, Enrique Javier. Universidad de Valencia; EspañaFil: Keunchkarian, Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; ArgentinaFil: Reta, Mario Roberto. Universidad Nacional de La Plata. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Herrero Martinez, José Manuel. Universidad de Valencia; Españ