Co-Expression of α9β1 Integrin and VEGF-D Confers Lymphatic Metastatic Ability to a Human Breast Cancer Cell Line MDA-MB-468LN

INTRODUCTION AND OBJECTIVES: Lymphatic metastasis is a common occurrence in human breast cancer, mechanisms remaining poorly understood. MDA-MB-468LN (468LN), a variant of the MDA-MB-468GFP (468GFP) human breast cancer cell line, produces extensive lymphatic metastasis in nude mice. 468LN cells differentially express α9β1 integrin, a receptor for lymphangiogenic factors VEGF-C/-D. We explored whether (1) differential production of VEGF-C/-D by 468LN cells provides an autocrine stimulus for cellular motility by interacting with α9β1 and a paracrine stimulus for lymphangiogenesis in vitro as measured with capillary-like tube formation by human lymphatic endothelial cells (HMVEC-dLy); (2) differential expression of α9 also promotes cellular motility/invasiveness by interacting with macrophage derived factors; (3) stable knock-down of VEGF-D or α9 in 468LN cells abrogates lymphangiogenesis and lymphatic metastasis in vivo in nude mice. RESULTS: A comparison of expression of cyclo-oxygenase (COX)-2 (a VEGF-C/-D inducer), VEGF-C/-D and their receptors revealed little COX-2 expression by either cells. However, 468LN cells showed differential VEGF-D and α9β1 expression, VEGF-D secretion, proliferative, migratory/invasive capacities, latter functions being stimulated further with VEGF-D. The requirement of α9β1 for native and VEGF-D-stimulated proliferation, migration and Erk activation was demonstrated by treating with α9β1 blocking antibody or knock-down of α9. An autocrine role of VEGF-D in migration was shown by its impairment by silencing VEGF-D and restoration with VEGF-D. 468LN cells and their soluble products stimulated tube formation, migration/invasiveness of HMVEC-dLy cell in a VEGF-D dependent manner as indicated by the loss of stimulation by silencing VEGF-D in 468LN cells. Furthermore, 468LN cells showed α9-dependent stimulation of migration/invasiveness by macrophage products. Finally, capacity for intra-tumoral lymphangiogenesis and lymphatic metastasis in nude mice was completely abrogated by stable knock-down of either VEGF-D or α9 in 468LN cells. CONCLUSION: Differential capacity for VEGF-D production and α9β1 integrin expression by 468LN cells jointly contributed to their lymphatic metastatic phenotype

Vergleich der Reanimationsqualität von Personen mit AED-Vorerfahrung bei konventioneller Audio- vs. Audio/Video- Anleitung durch einen automatischen externen Defibrillator (AED)

Hintergrund: Ein automatischer externer Defibrillator (AED) bietet während der Reanimation (CPR) zusätzlich zur akustischen auch eine kontinuierliche visuelle Anleitung. Ziel der Studie war es, bei ProbandInnen mit AED-Vorerfahrung mögliche Unterschiede in der Reanimationsqualität unter Verwendung des neuartigen AEDs zu erheben. Methoden: In den ersten Wochen ihres Medizinstudiums wurden 109 MedizinstudentInnen mit einem AED ausgestattet, um 4 Minuten lang Einhelfer-CCO-CPR (Chest-Compression-Only) an einer Reanimationspuppe durchzuführen. Die Teilnehmer wurden in 2 Interventionsgruppen randomisiert. Eine Gruppe erhielt den AED mit konventioneller Audioanleitung, eine den mit zusätzlicher Videoanleitung. Primäres Ziel war die Erhebung der CPR-Qualität durch die Effective-Compression-Ratio (ECR). Bei korrekt durchgeführter CCO-CPR beträgt die maximal zu erreichende ECR 0,92. Zusätzlich wurden subjektive Fragestellungen zur durchgeführten Reanimation mittels Likert-Skala von 1 („sehr schlecht“) bis 10 („sehr gut“) erhoben. Resultate: Im aufgezeichneten Intervall beträgt die ECR in der Gruppe der ProbandInnen, die den AED mit reiner Audioanleitung benutzten 0,15, und in der Gruppe mit zusätzlicher Videoanleitung 0,12 (p=0,489). In keinem der Qualitätsparameter liegt ein signifikanter Unterschied zwischen den beiden Interventionsgruppen vor. Die Gruppe mit zusätzlicher Videoanleitung (Median 10) fühlt sich jedoch subjektiv durch den AED besser unterstützt als die Gruppe mit rein akustischer Anleitung (Median 9). (p=0,035) Diskussion: Es zeigt sich kein Unterschied in der Reanimationsqualität zwischen den beiden Interventionsgruppen. Die zusätzliche Videoanleitung wird jedoch als unterstützend empfunden. Dies könnte vor allem Ersthelfern ohne AED-Erfahrung helfen, diesen richtig zu bedienen. Weitere Studien sollten sich mit dem Einfluss des Videos auf andere Bevölkerungsgruppen beschäftigen.Purpose of this Study: An automated external defibrillator (AED) with an integrated video screen gives additional visual instruction during CPR. The aim of our study was to evaluate possible differences in CPR-quality when using the AED with additional video instructions in comparison to conventional AED with voice prompts only. Methods: In their very first weeks of university, 109 medicine students with prior experience with an AED were randomized into two groups: Audio only (54) and audio plus video (55) AED during a 4-minute single rescuer chest-compression only (CCO) CPR on a manikin. Primary goal was to assess CPR-quality using the combined parameter Effective-Compression-Ratio (ECR). In this setting, perfectly executed CPR would reach a maximum ECR of 0,92. Via a case report form (CRF) subjective opinions on the just performed CPR were assessed on a 10-point Likert scale (lowest = 0 to highest = 10). Results: ECR did not differed significantly between the two groups. The audio-only group reached a ECR of 0,15, and the audio-video group an ECR of 0,12 (p=0,489). In the subjective question on how supportive the instruction of the AED was, the audio-video group felt significantly better supported. Median in the audio-video group was 10, and 9 in the audio-only group (p= 0,035). Discussion: No difference in CPR-quality between the 2 groups was found. However, the additional visual instructions seem to result in a better subjective feeling during CPR. This could especially help bystanders with no AED-experience. Further studies should examine the influence of the additional video-instructions on different population groups.eingereicht von Constantin SonvillaAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Diplomarb., 2018(VLID)249035

Supporting energy efficiency measures in the residential sector. The case of on-bill schemes

none2Implementation of energy efficiency interventions in the residential sector is pivotal to drive the energy transition and achieve energy policy targets. For such a reason, public programs supporting the renovation of residential buildings are available globally, but public incentives are not enough to address all the potential and it is necessary to attract private investments. An innovative approach to consider is represented by on-bill schemes, which foresee investments by energy utilities with possible cooperation of financial institutions. The present contribution proposes an in-depth description of on-bill mechanisms, their possible frameworks, the barriers to their implementation as well as the impact they may have on the core business of utilities. The study is based on a review of the existing literature integrated with the results of on-field interviews and discussions with the aim to obtain a full picture of on-bill schemes in a European replication perspective. Methodologically, the paper is based on structured desk research and on-field feedback obtained from selected stakeholders. Additionally, a SWOT analysis is developed highlighting that on-bill schemes may result very convenient for power utilities and energy retailers. Furthermore, on-bill schemes can help to address the issue of the split incentives. In conclusion, on-bill schemes can be considered a valid tool to support energy renovation in the residential sector, but they do not represent a global solution since their application is not tailored for all the contexts. The analysis highlights that power utilities are in a strong position since they can use on-bill schemes to switch part of the demand from fossil fuels, e.g., natural gas, to electrical power. Similarly, energy retailers are in a good position since they can enlarge their business by selling energy efficiency as a service through on-bill schemes.openBianco V.; Sonvilla P.M.Bianco, V.; Sonvilla, P. M

Future Learning Spaces: Designs on elearning conference proceedings 2011

This publication is a collection of papers, projects and performances presented at DoEL 2011 conference "Future Learning Spaces", which was held from 27.09-30.09. at TAIK.Peer reviewe

Can distributor system operators play a role in the European Union energy efficiency financing game?

On-bill schemes are innovative financial frameworks for supporting energy renovation based on private capital. Direct intervention of public authorities may not be necessary. The pivotal role is assumed by energy utilities which are the originators of the business and act as market aggregators. On-bill schemes are based on a simple principle, namely the utility supports the energy renovation of final users by providing the upfront capital to repay on the utility bill. This implies that energy supply and renovation services are provided by the same company. This could be a limitation since the user may be obliged to stay with the same energy supplier for all the duration of the on-bill scheme. Even more complications can arise when the dwelling is sold or rent to another tenant. For such a reason it is important to find solutions for the possible decoupling of energy supply and energy renovation services. The present paper introduces an innovative business model which involves Distribution System Operators or other designated entities acting as market facilitators supporting the decoupling between energy supply and building energy renovation services. To characterise precisely the business ecosystem and the relations among the different actors, the Value Flow Model is employed

Business models for supporting energy renovation in residential buildings. The case of the on-bill programs

On-bill schemes are innovative financial frameworks for supporting investments in energy efficiency with a particular focus on residential buildings. These schemes are interesting since they allow to attract private capital in the energy efficiency market, and they also see the involvement of energy utilities which can be regarded as market aggregators. Despite the conceptual simplicity of these mechanisms, namely the utility provides upfront capital for the investment which is repaid by final users on the bill in a number of years, solid and innovative business models are necessary to support their development and implementation. To this aim the present paper employs the Value Flow Model to develop four business models to implement on-bill schemes. In particular, standard on-bill financing and on-bill repayment business models are developed in detail. In addition, more complicated and innovative business models, namely on-bill repayment via a Special Purpose Vehicle and on-bill repayment with a Master Servicer, are also developed for more complex schemes. These four fundamental business models can be used and adapted according to market context of operation. Finally, the possible involvement of Distribution System Operators as service providers or facilitators for on-bill schemes is also outlined