On the preservation of vessel bifurcations during flow-mediated angiogenic remodelling

During developmental angiogenesis, endothelial cells respond to shear stress by migrating and remodelling the initially hyperbranched plexus, removing certain vessels whilst maintaining others. The key regulator of vessel preservation is cell decision behaviour at bifurcations. At flow-convergent bifurcations where migration paths diverge, cells must finely tune migration along both possible paths if the bifurcation is to persist. Experiments have demonstrated that disrupting the cells’ ability to sense shear or junction forces transmitted between cells impacts the preservation of bifurcations during the remodelling process. However, how these migratory cues integrate during cell decision making remains poorly understood. Therefore, we present the first agent-based model of endothelial cell flow-mediated migration suitable for interrogating the mechanisms behind bifurcation stability. The model simulates flow in a bifurcated vessel network composed of agents representing endothelial cells arranged into a lumen which migrate against flow. Upon approaching a bifurcation where more than one migration path exists, agents refer to a stochastic bifurcation rule which models the decision cells make as a combination of flow-based and collective-based migratory cues. With this rule, cells favour branches with relatively larger shear stress or cell number. We found that cells must integrate both cues nearly equally to maximise bifurcation stability. In simulations with stable bifurcations, we found competitive oscillations between flow and collective cues, and simulations that lost the bifurcation were unable to maintain these oscillations. The competition between these two cues is haemodynamic in origin, and demonstrates that a natural defence against bifurcation loss during remodelling exists: as vessel lumens narrow due to cell efflux, resistance to flow and shear stress increases, attracting new cells to enter and rescue the vessel from regression. Our work provides theoretical insight into the role of junction force transmission has in stabilising vasculature during remodelling and as an emergent mechanism to avoid functional shunting

PolNet Analysis: a software tool for the quantification of network-level endothelial cell polarity and blood flow during vascular remodelling

In this paper, we present PolNet, an open source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterise the haemodynamics of the vascular networks under study. The tool enables, for the first time, network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarisation and migration during vascular patterning, as demonstrated by our recent papers (Franco 2015, Franco 2016a). Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the LGPL licence

Tyrosine-protein kinase Yes controls endothelial junctional plasticity and barrier integrity by regulating VE-cadherin phosphorylation and endocytosis

Vascular endothelial (VE)-cadherin in endothelial adherens junctions is an essential component of the vascular barrier, critical for tissue homeostasis and implicated in diseases such as cancer and retinopathies. Inhibitors of Src cytoplasmic tyrosine kinase have been applied to suppress VE-cadherin tyrosine phosphorylation and prevent excessive leakage, edema and high interstitial pressure. Here we show that the Src-related Yes tyrosine kinase, rather than Src, is localized at endothelial cell (EC) junctions where it becomes activated in a flow-dependent manner. EC-specific Yes1 deletion suppresses VE-cadherin phosphorylation and arrests VE-cadherin at EC junctions. This is accompanied by loss of EC collective migration and exaggerated agonist-induced macromolecular leakage. Overexpression of Yes1 causes ectopic VE-cadherin phosphorylation, while vascular leakage is unaffected. In contrast, in EC-specific Src deficiency, VE-cadherin internalization is maintained and leakage is suppressed. In conclusion, Yes-mediated phosphorylation regulates constitutive VE-cadherin turnover, thereby maintaining endothelial junction plasticity and vascular integrity

Physics with the KLOE-2 experiment at the upgraded DAϕ\phiNE

Investigation at a $\phi$--factory can shed light on several debated issues in particle physics. We discuss: i) recent theoretical development and experimental progress in kaon physics relevant for the Standard Model tests in the flavor sector, ii) the sensitivity we can reach in probing CPT and Quantum Mechanics from time evolution of entangled kaon states, iii) the interest for improving on the present measurements of non-leptonic and radiative decays of kaons and eta/eta$^\prime$ mesons, iv) the contribution to understand the nature of light scalar mesons, and v) the opportunity to search for narrow di-lepton resonances suggested by recent models proposing a hidden dark-matter sector. We also report on the $e^+ e^-$ physics in the continuum with the measurements of (multi)hadronic cross sections and the study of gamma gamma processes.Comment: 60 pages, 41 figures; added affiliation for one of the authors; added reference to section

Shock−induced arrhythmogenesis in the human heart: a computational modelling study

Electrical defibrillation by application of a strong shock to the heart is the only effective treatment against lethal cardiac arrhythmias such as ventricular fibrillation. A large body of experimental and computational research has been devoted to understanding shock-induced effects on the heart in an attempt to improve defibrillation efficacy. However, most of the research has been performed in small animal hearts, and in particular rabbits. The difference in size between rabbits and humans might limit the extrapolation of the results to the clinical setting. In this paper, we present, for the first time, computer simulations of shock-induced effects on a human ventricular model with realistic ion channel dynamics and fibre architecture. Bidomain simulations using the human ventricular model were performed using the Chaste open source simulation package. The parallel performance of the software package was highly improved in order to meet the computational requirements of these kind of studies

Sähkötilojen kuntokartoitus

Opinnäytetyö käsittelee Tampereen Energiantuotanto Oy:n Pirkanmaan alueella sijaitsevien kiinteiden lämpökeskusten sähkötilojen ja muun valitun sähkölaitteiston kuntokartoitusta ja parannusehdotusten kustannusarviota. Työn tavoitteena oli kerätä tiivis tietopaketti lämpökeskusten sähkölaitteiston kunnosta ja tehdä parannusehdotuksista kustannusarviot päätöksenteon tueksi. Tavoitteisiin pyrittiin tutustumalla voimassa oleviin standardeihin, turvallisuusmääräyksiin ja tarkastuskäytäntöihin sekä laatimalla tarkastuspöytäkirja. Tarkastuspöytäkirjojen pohjalta tehtiin yhteenvedot ja sähkölaitteiston parannusehdotukset. Parannusehdotusten kustannusarviot koottiin käyttämällä tuotteiden listahintoja ja tilaajan varastohenkilökunnalta ja asiantuntijoilta saatuja tietoja. Tarkastettu sähkölaitteisto oli laaja ja asennettu viidellä eri vuosikymmenellä. Laitteistossa oli hyvä-, tyydyttävä- ja välttäväkuntoisia laitteita. Yhtään huonokuntoista laitteistoa, jolla olisi välitön uusimis- tai korjaustarve, ei löytynyt. Kustannusarviot olivat n. 100–50 000 €. Suurin osa kustannusarvioiden summista oli minimaalisia, muutamia satoja euroa. Kustannusarvioiden suurimmat summat olivat Julkujärven ja Hervannan lämpökeskuksien parannusehdotuksilla. Johtopäätöksenä todettiin, että sähkölaitteisto oli yleisesti hyväkuntoinen. Julkujärven ja Hervannan lämpökeskusten parannusehdotusten pohjalta olisi hyvä tehdä lisätutkimuksia, joiden avulla selvitettäisiin uudistus- tai korjaustarve yksityiskohtaisemmin. Lisätutkimukset auttaisivat laitteiston lopullisen kunnostus- ja parannusohjelman laatimisessa.This bachelor’s thesis is about condition audit, proposals for improvements and estimates of their prices in Tampereen Energiantuotanto Ltd.’s fixed heating plants in Pirkanmaa area. The goals were to gather a compact information package about the condition of electrical installations and to estimate the costs of proposals for improvements to support decision making. In order to meet these goals valid standards, safety regulations and running practice were studied and audit minutes were compiled. Based on the minutes summaries and proposals for improvements were made. When estimating the costs of the improvement proposals, retail prices and the warehouse staff’s as well as expert’s knowledge were taken into account. The number of inspected electrical installations was high. The installations had been made in five decades. Electrical installations in good, satisfactory and tolerable conditions were found. There were no installations which would have been in bad condition and would have needed immediate repair. The cost estimates were between 100–50 000 €. The most of the cost estimates were small sums, a few hundred euros. In Julkujärvi and Hervanta heating plants cost estimates were the largest ones. As a conclusion the condition of electrical installations was good in general. In Julkujärvi and Hervanta heating plants further detections should be made in more detailed way in order to make renovation and improvement plans for the installation