Aspects of nucleolar metabolism in herpesvirus infected cells

The inhibition of ribosomal RNA production has been studied in Hela cells infected with pseudorabies virus (PrV). This showed that both synthesis and processing of ribosomal RNA was affected. Processing in PrV-infected Hela cells was at a reduced rate but did follow a similar pattern to that of mock-infected cells. The effect on synthesis of ribosomal RNA was more pronounced and was followed by a concomitant decrease in the total nucleolar area of the infected Hela cells. Polyacrylamide gel electrophoresis of fractions from mock-infected and PrV-infected Hela cells showed that a number of virus induced polypeptides were associated with the nucleus, nucleolus and the nucleolar chromatin. Some of these polypeptides were immediate early viral gene products. A number of viral induced polypeptides were shown to be associated with the nuclei and nucleoli of mock-infected Hela cells after incubation in vitro of isolated nuclei and cell extracts of both mock-infected and infected Hela cells. The RNA polymerase activity of isolated nuclei of PrV- infected Hela cells was lower than that of mock-infected. This was true both for total and for a-amanitin resistant activities. The difference in RNA polymerase activity between mock-infected and infected Hela cells remained unchanged after incubation of the nuclei in the presence of the detergent sarkosyl. Again incubation in the presence of extracts of mock-infected or infected cells did not alter relative activities in the normal assay whereas RMA polymerase activity in mock-infected Hela cell nuclei was reduced after a combined exposure to infected cell extracts followed by treatment with aarkosyl. This suggests that its inhibition of ribosomal RNA synthesis in Hela cells after infection with pseudorabies virus is by interference at the initiation level of the transcription process rather than the elongation level. It may be mediated by a viral-induced protein(s) associated with the nucleolar and nucleolar chromatin cell fractions

Simulation of atherosclerotic plaque growth using computational biomechanics and patient-specific data

Atherosclerosis is the one of the major causes of mortality worldwide, urging the need for prevention strategies. In this work, a novel computational model is developed, which is used for simulation of plaque growth to 94 realistic 3D reconstructed coronary arteries. This model considers several factors of the atherosclerotic process even mechanical factors such as the effect of endothelial shear stress, responsible for the initiation of atherosclerosis, and biological factors such as the accumulation of low and high density lipoproteins (LDL and HDL), monocytes, macrophages, cytokines, nitric oxide and formation of foams cells or proliferation of contractile and synthetic smooth muscle cells (SMCs). The model is validated using the serial imaging of CTCA comparing the simulated geometries with the real follow-up arteries. Additionally, we examine the predictive capability of the model to identify regions prone of disease progression. The results presented good correlation between the simulated lumen area (P<0.0001), plaque area (P<0.0001) and plaque burden (P<0.0001) with the realistic ones. Finally, disease progression is achieved with 80% accuracy with many of the computational results being independent predictors

Non-Invasive Prediction of Site-Specific Coronary Atherosclerotic Plaque Progression using Lipidomics, Blood Flow, and LDL Transport Modeling

Background: coronary computed tomography angiography (CCTA) is a first line non-invasive imaging modality for detection of coronary atherosclerosis. Computational modeling with lipidomics analysis can be used for prediction of coronary atherosclerotic plaque progression. Methods: 187 patients (480 vessels) with stable coronary artery disease (CAD) undergoing CCTA scan at baseline and after 6.2 +/- 1.4 years were selected from the SMARTool clinical study cohort (Clinicaltrial.gov Identifiers NCT04448691) according to a computed tomography (CT) scan image quality suitable for three-dimensional (3D) reconstruction of coronary arteries and the absence of implanted coronary stents. Clinical and biohumoral data were collected, and plasma lipidomics analysis was performed. Blood flow and low-density lipoprotein (LDL) transport were modeled using patient-specific data to estimate endothelial shear stress (ESS) and LDL accumulation based on a previously developed methodology. Additionally, non-invasive Fractional Flow Reserve (FFR) was calculated (SmartFFR). Plaque progression was defined as significant change of at least two of the morphological metrics: lumen area, plaque area, plaque burden. Results: a multi-parametric predictive model, including traditional risk factors, plasma lipids, 3D imaging parameters, and computational data demonstrated 88% accuracy to predict site-specific plaque progression, outperforming current computational models. Conclusions: Low ESS and LDL accumulation, estimated by computational modeling of CCTA imaging, can be used to predict site-specific progression of coronary atherosclerotic plaques.</div

La revuelta del General Casiano en Mesotinia (1306)

The first decade of the fourteenth century was a period of political, military and financial crisis in Byzantium. The inability of the government of Andronikos II Palaiologos (1282-1328) to resist the expansion of the Turcoman principalities caused the dissatisfaction of the Anatolian soldiers and resulted in a series of revolts and conspiracies. One of these was the revolt of Kassianos in Mesothynia in 1306. The analysis of this local rebellion contributes to the better understanding of the military developments in Asia Minor in the first decade of the fourteenth century.La primera década del siglo XIV fue un período de crisis política, militar y financiera en Bizancio. La incapacidad del gobierno de Andrónico II Paleólogo (1282-1228) de resistir la expansión de los principados turcomanos causó la insatisfacción de los soldados anatolios y tuvo como consecuencia una serie de revueltas y conspiraciones. Una de ellas fue la revuelta de Casiano en Mesopotamia en 1306. El análisis de esta rebelión local contribuye a una mejor comprensión de los desarrollos militares en Asia Menor en la primera década del siglo XIV

The battle exhortation in Byzantine historiography (10th-12th centuries)

This paper focuses on the function of battle exhortations that are found in the works of Byzantine historians, who on occasion have military leaders address large audiences of soldiers who were ready to engage in battle. The analysis of the topoi that can be found in these works lead to useful conclusions regarding Byzantine ideas about military leadership and morale.Este artículo estudia la función de las arengas de combate que encontramos en las obras de los historiadores bizantinos, que en ocasio - nes presentan discursos militares dirigidos a grandes masas de soldados listos para entablar combate. El análisis de los lugares comunes presentes en estas obras conduce a conclusiones útiles acerca de las ideas bizantinas sobre el caudillaje militar y la moral

Aσθενής με Παραμένουσα Αριστερή Άνω Κοίλη Φλέβα, Υπερκοιλιακή Ταχυκαρδία Κομβικής Επανεισόδου (ΑVNRT) και Παροξυσμική Υπερκοιλιακή Ταχυκαρδία κ-Κ Επανεισόδου (AVRT) από Κεκρυμμένο Αριστερό Πλάγιο Δεμάτιο

Ασθενής 70 ετών παραπέμφθηκε στο Νοσοκομείο μας λόγω συχνών επεισοδίων παροξυσμικής υπερκοιλιακής ταχυκαρδίας, με ένδειξη για ηλεκτροφυσιολογική μελέτη και κατάλυση. Το ηλεκτροκαρδιογράφημα (ΗΚΓ) επί του παροξυσμού παρουσιάζει ρυθμική ταχυκαρδία με στενό σύμπλεγμα QRS, συχνότητα 170 σφύξεις/min και ορατή κολπική δραστηριότητα στο ST διάστημα με χρόνο RP 140 ms και κύμα P αρνητικό στις απαγωγές Ι, AVL και θετικό στις απαγωγές ΑVR και V1, ενδεικτικό για κυκλική ταχυκαρδία με συμμετοχή εκτόπου δεματίου στο ελεύθερο τοίχωμα της αρ. κοιλίας (Eικ. 1) Το ΗΚΓ εκτός παροξυσμού ήταν φυσιολογικό... (excerpt

IVUS Longitudinal and Axial Registration for Atherosclerosis Progression Evaluation

Intravascular ultrasound (IVUS) imaging offers accurate cross-sectional vessel information. To this end, registering temporal IVUS pullbacks acquired at two time points can assist the clinicians to accurately assess pathophysiological changes in the vessels, disease progression and the effect of the treatment intervention. In this paper, we present a novel two-stage registration framework for aligning pairs of longitudinal and axial IVUS pullbacks. Initially, we use a Dynamic Time Warping (DTW)-based algorithm to align the pullbacks in a temporal fashion. Subsequently, an intensity-based registration method, that utilizes a variant of the Harmony Search optimizer to register each matched pair of the pullbacks by maximizing their Mutual Information, is applied. The presented method is fully automated and only required two single global image-based measurements, unlike other methods that require extraction of morphology-based features. The data used includes 42 synthetically generated pullback pairs, achieving an alignment error of 0.1853 frames per pullback, a rotation error 0.93° and a translation error of 0.0161 mm. In addition, it was also tested on 11 baseline and follow-up, and 10 baseline and post-stent deployment real IVUS pullback pairs from two clinical centres, achieving an alignment error of 4.3±3.9 for the longitudinal registration, and a distance and a rotational error of 0.56±0.323 mm and 12.4°±10.5°, respectively, for the axial registration. Although the performance of the proposed method does not match that of the state-of-the-art, our method relies on computationally lighter steps for its computations, which is crucial in real-time applications. On the other hand, the proposed method performs even or better that the state-of-the-art when considering the axial registration. The results indicate that the proposed method can support clinical decision making and diagnosis based on sequential imaging examinations

OCT sequence registration before and after percutaneous coronary intervention (stent implantation)

To assess the progression of coronary artery disease, Optical Coherence Tomography (OCT) pullbacks acquired at different timepoints should be compared. However, the assessment of temporal sequences is a difficult task, as motion artifacts in the longitudinal and axial plane can decrease the quality of the manual inspection. To address this challenge, the current study presents a two-stage computational framework for the longitudinal and axial registration of two OCT pullbacks. During the first stage of the process, we focus on the accurate detection of the matching image pairs from the respective series, while during the second stage we focus on the axial registration of the matched pairs so that their common features are aligned. The dataset used includes 19 patients from two clinical centers, with two OCT pullbacks per patient: one before the stent implantation procedure and one after it. We applied our method on a synthetic dataset of OCT pullbacks, which was generated based on the in-vivo OCT pullbacks to reproduce the motion artifacts across the planes. In addition, the proposed method was validated on the 19 pairs of in-vivo OCT pullbacks with annotated pre/post stent deployment data. The method was able to reduce the alignment error from 32.17±26.14 to 5.6±6.6 frames, the rotational error from 11.59°±11.22° to 1.18°±0.81° and the distance error from 3.07mm±1.52mm to 0.46mm±0.44mm. In addition, the mean Mutual Information similarity increased by 13.47% after the longitudinal registration and an additional 123.33% after the axial registration on top of the previous one

Error Propagation in the Simulation of Atherosclerotic Plaque Growth and the Prediction of Atherosclerotic Disease Progression

Assessments of coronary artery disease can be achieved using non-invasive computed tomography coronary angiography (CTCA). CTCA can be further used for the 3D reconstruction of the coronary arteries and the development of computational models. However, image acquisition and arterial reconstruction introduce an error which can be propagated, affecting the computational results and the accuracy of diagnostic and prognostic models. In this work, we investigate the effect of an imaging error, propagated to a diagnostic index calculated using computational modelling of blood flow and then to prognostic models based on plaque growth modelling or binary logistic predictive modelling. The analysis was performed utilizing data from 20 patients collected at two time points with interscan period of six years. The collected data includes clinical and risk factors, biological and biohumoral data, and CTCA imaging. The results demonstrated that the error propagated and may have significantly affected some of the final outcomes. The calculated propagated error seemed to be minor for shear stress, but was major for some variables of the plaque growth model. In parallel, in the current analysis SmartFFR was not considerably affected, with the limitation of only one case located into the gray zone

A proof-of-concept study for the simulation of blood flow in a post arterial segment for different blood rheology models

: Cardiovascular disease (CVD) and especially atherosclerosis are chronic inflammatory diseases which cause the atherosclerotic plaque growth in the arterial vessels and the blood flow reduction. Stents have revolutionized the treatment of this disease to a great extent by restoring the blood flow in the vessel. The present study investigates the performance of the blood flow after stent implantation in patient-specific coronary artery and demonstrates the effect of using Newtonian vs. non-Newtonian blood fluid models in the distribution of endothelial shear stress. In particular, the Navier-Stokes and continuity equations were employed, and three non-Newtonian fluid models were investigated (Carreau, Carreau-Yasuda and the Casson model). Computational finite elements models were used for the simulation of blood flow. The comparison of the results demonstrates that the Newtonian fluid model underestimates the calculation of Endothelial Shear Stress, while the three non-Newtonian fluids present similar distribution of shear stress. Keywords: Blood flow dynamics, stented artery, non-Newtonian fluid. Clinical Relevance- This work demonstrates that when blood flow modeling is performed at stented arteries and predictive models are developed, the non-Newtonian nature of blood must be considered