Tissue-resident memory T cells orchestrate tumour-immune equilibrium

The immune system can prevent tumour development by engaging in a process termed cancer immunosurveillance, during which immune cells such as T cells restrict tumour growth either by completely eradicating cancer cells in a process of ‘elimination’ or by suppressing cancer cell outgrowth by establishing a state of tumour-immune ‘equilibrium’. Most cancers develop within epithelial layers of tissues but circulating T cells are largely excluded from these epithelial tissue compartments in the absence of infection or overt inflammation. In contrast, CD8+ tissue-resident memory T (TRM) cells reside permanently within epithelial layers of peripheral tissues without recirculating in blood. Accumulating evidence suggests that TRM cells are found in diverse human solid cancers where they correlate with improved prognosis and can protect against tumour challenge in mice. However, the mechanisms through which these cells mediate cancer protection are poorly understood. In our recent study (Park SL et al, Nature 565(7739), 2019) we developed a melanoma model that allowed us to identify a critical role for TRM cells in the establishment and maintenance of tumour-immune equilibrium in skin. Our findings provide insight into the immune cell populations important for maintaining long-term tumour dormancy in peripheral tissues and imply that targeting TRM cells may serve as a novel cancer treatment strategy

Potentials of Light Electric Vehicles for Climate Protection by Substituting Passenger Car Trips

For the transformation of the mobility sector, small and light electric vehicles (LEV) show great promise, owing to their efficiency and low vehicle weight resulting in low energy consumption and lower greenhouse gas emissions per driven kilometer. The presented study focuses on the theoretical potential of substitutability of passenger car trips in Germany by varied LEVs based on the “Mobilität in Deutschland 2017” (“Mobility in Germany 2017”) dataset, for the year 2030. A detailed approach for identifying substitutable car trips was developed, reflecting age, trip purpose, number of passengers, and other decision criteria. By conducting a life cycle assessment of the considered LEVs and passenger cars, potential emission savings were analyzed. In the considered baseline scenario, it is found that emissions could be reduced by 44 % with 50% of passenger car mileage being substitute by LEVs. This study, thereby, gives way to further research on LEVs, and would urge both policy makers and general users to steer towards comprehensive measures that encourage a switch from cars to LEVs

The Potential of Light Electric Vehicles for Climate Protection through Substitution for Passenger Car Trips - Germany as a Case Study

This presentation summarizes the results of the LEV4Climate Study. Light electric vehicles can reduce greenhouse gas emissions by replacing large and heavy vehicles. Emissions decrease for replacement of passenger cars with any type of propulsion, albeit to different extents. In order to quantify the theoretical potential of emission reduction, this study models a scenario in 2030, in which a major modal shift away from trips with full-sized passenger cars to LEVs has taken place. This analysis assumes today’s patterns of mobility are maintained, but using full sized cars only for those few trips which are very long or include many occupants. The work employs Germany as a case study for potential savings, given the national importance of cars as both a means of mobility and an economic sector. Statistical data from a representative national survey serves as the basis for analysing which car trips can be substituted with LEVs. We use the characteristics of vehicles (e.g. speed, range, number of seats) and trips (e.g. distance) to determine which trips may be conducted in LEVs, and thus derive a total for substitutable car kilometers. Together with an assessment of greenhouse gas emissions per vehicle kilometer for both LEVs and the replaced vehicles (considering production via life cycle analyses and energy for vehicle use), a theoretical, calculative potential of greenhouse gas emissions savings is derived for Germany. The analysis shows that up to 50 % of car mileage could be replaced with LEVs which corresponds to up to 44 % savings of greenhouse gas emissions

Deregulation of Rab and Rab Effector Genes in Bladder Cancer

Growing evidence indicates that Rab GTPases, key regulators of intracellular transport in eukaryotic cells, play an important role in cancer. We analysed the deregulation at the transcriptional level of the genes encoding Rab proteins and Rab-interacting proteins in bladder cancer pathogenesis, distinguishing between the two main progression pathways so far identified in bladder cancer: the Ta pathway characterized by a high frequency of FGFR3 mutation and the carcinoma in situ pathway where no or infrequent FGFR3 mutations have been identified. A systematic literature search identified 61 genes encoding Rab proteins and 223 genes encoding Rab-interacting proteins. Transcriptomic data were obtained for normal urothelium samples and for two independent bladder cancer data sets corresponding to 152 and 75 tumors. Gene deregulation was analysed with the SAM (significant analysis of microarray) test or the binomial test. Overall, 30 genes were down-regulated, and 13 were up-regulated in the tumor samples. Five of these deregulated genes (LEPRE1, MICAL2, RAB23, STXBP1, SYTL1) were specifically deregulated in FGFR3-non-mutated muscle-invasive tumors. No gene encoding a Rab or Rab-interacting protein was found to be specifically deregulated in FGFR3-mutated tumors. Cluster analysis showed that the RAB27 gene cluster (comprising the genes encoding RAB27 and its interacting partners) was deregulated and that this deregulation was associated with both pathways of bladder cancer pathogenesis. Finally, we found that the expression of KIF20A and ZWINT was associated with that of proliferation markers and that the expression of MLPH, MYO5B, RAB11A, RAB11FIP1, RAB20 and SYTL2 was associated with that of urothelial cell differentiation markers. This systematic analysis of Rab and Rab effector gene deregulation in bladder cancer, taking relevant tumor subgroups into account, provides insight into the possible roles of Rab proteins and their effectors in bladder cancer pathogenesis. This approach is applicable to other group of genes and types of cancer

Can shared E-scooters reduce CO2 emissions by substituting car trips in Germany?

This paper explores which trips currently made in Germany by personal motorized transportation could be replaced by e-scooters and what effect this would have on greenhouse gas emissions. This potential for substitution is estimated on the basis of data from the national household travel survey in Germany. Our analysis shows that 13% of the daily car trips, corresponding to 2% of the car kilometers in Germany, are suitable for replacement. Based on these results, we show that saving potentials of greenhouse gas emissions are heavily dependent on the general conditions of the specific use case (e.g. e-scooter lifetime) and the type of vehicle replaced. At best, a saving potential of about 5.8 kt of CO2eq per day could be achieved when trips with conventional cars are replaced by e-scooter driving. However, if battery electric cars are replaced, an increase in emissions may even occur under certain conditions

The Potential of Light Electric Vehicles for Climate Protection through Substitution for Passenger Car Trips - Germany as a Case Study

Light electric vehicles can reduce greenhouse gas emissions by replacing large and heavy vehicles. Emissions decrease for replacement of passenger cars with any type of propulsion, albeit to different extents. In order to quantify the theoretical potential of emission reduction, this study models a scenario in 2030, in which a major modal shift away from trips with full-sized passenger cars to LEVs has taken place. This analysis assumes today’s patterns of mobility are maintained, but using full sized cars only for those few trips which are very long or include many occupants. The work employs Germany as a case study for potential savings, given the national importance of cars as both a means of mobility and an economic sector. Statistical data from a representative national survey serves as the basis for analysing which car trips can be substituted with LEVs. We use the characteristics of vehicles (e.g. speed, range, number of seats) and trips (e.g. distance) to determine which trips may be conducted in LEVs, and thus derive a total for substitutable car kilometers. Together with an assessment of greenhouse gas emissions per vehicle kilometer for both LEVs and the replaced vehicles (considering production via life cycle analyses and energy for vehicle use), a theoretical, calculative potential of greenhouse gas emissions savings is derived for Germany. The analysis shows that up to 50 % of car mileage could be replaced with LEVs which corresponds to up to 44 % savings of greenhouse gas emissions

E-Scooter - Potentiale, Herausforderungen und Implikationen für das Verkehrssystem: Abschlussbericht Kurzstudie E-Scooter

In Deutschland werden mit dem Pkw täglich fast 30 Mio. Fahrten unter 2 km zurückgelegt. Weitere rund 30 Mio. Pkw-Fahrten sind unter 5 km lang. Im Sinne einer nachhaltigen, städtischen Mobilität gilt es die Frage zu beantworten, wie bzw. mit welchen alternativen Verkehrsmitteln diese kurzen Strecken zurückgelegt werden könnten. Als ein Lösungsansatz werden, seit ihrer Straßenzulassung im Juni 2019, in Deutschland elektrische Tretroller, die sogenannten E-Scooter, diskutiert. Mit der Einführung der E-Scooter war die Hoffnung verbunden, dass sie als ein Baustein nachhaltiger, multimodaler Mobilität einen Beitrag zur angestrebten Verkehrswende leisten. Da E-Scooter ohne lokale Emissionen betrieben werden, können sie einen Beitrag zur Verbesserung der innerstädtischen Luftqualität leisten, insbesondere, wenn konventionelle Pkw-Fahrten substituiert werden. Darüber hinaus stellt sich die Frage, inwieweit die Nutzung von E-Scootern die Treibhausgas-Emissionen des städtischen Verkehrs beeinflusst. Gleichzeitig gibt es aber auch kritische Stimmen, die die Nachhaltigkeit von E-Scootern in Frage stellen, da E-Scooter in Konkurrenz zu aktiver Mobilität und zum ÖV stehen. Zudem werden E-Scooter als Gefahr für andere Verkehrsteilnehmer:innen gesehen. Die Grundlage, auf der diese Diskussion stattfindet, ist bis dato wissenschaftlich nicht hinreichend fundiert. Nach wie vor fehlt es an Zahlen sowohl zur tatsächlichen Nutzung als auch zu Potentialen, bspw. in Hinblick auf eine Reduktion des motorisierten Individualverkehrs (MIV). Vor diesem Hintergrund gibt dieser Bericht einen Überblick über das bisherige Wissen zur E-Scooter-Nutzung sowie zu Implikationen, die mit der Nutzung einhergehen. Hierfür werden wissenschaftliche Studien und empirische Daten analysiert. Anhand einer Auswertung von Daten der Mobilitätserhebung MiD 2017 wird in einer Potentialanalyse das theoretische Substitutionspotential von E-Scootern für Wege, die bisher mit dem Pkw zurückgelegt werden, abgeschätzt. Diese Abschätzung ist gleichzeitig der Ausgangspunkt für die Analyse der Treibhausgasemissionen

Das Potenzial von Elektroleichtfahrzeugen für den Ersatz von Pkw-Fahrten - Deutschland als Fallbeispiel

Der Vortrag zeigt das Potenzial von Elektroleichtfahrzeugen (Light Electric Vehicles - LEV) für den Ersatz von Pkw-Fahrten in Deutschland auf und erläutert das methodische Vorgehen der zugehörigen Analysen