528 research outputs found
Role of tumor-derived extracellular vesicles in immunosuppression in malignant melanoma patients
Das Ziel dieser Studie war es die Rolle von extrazellulären Vesikeln (EVs) bei der Umwandlung von zirkulierenden CD14+ Monozyten in monozytäre myeloide suppressor Zellen (M-MDSCs) zu untersuchen. Dabei wurden EVs aus humanen Melanomzelllinien, sowie Plasma von Melanompatienten isoliert. Wir haben gezeigt, dass EVs von HT-144 Zellen (HT-144 EVs) Bcl-2 in CD14+ Monozyten hochregulierten (auf mRNA -und Proteinebene) und dieses eine anti-apoptotische Wirkung hatten. Darüber hinaus zeigten CD14+ Monozyten ein verstärktes Entzündungsprofil, sowie eine verstärkte Migration nach der Stimulation mit HT-144 EVs. Nach der Behandlung der Monozyten mit EVs aus HT-144 und SK-MEL-28 Zellen, wurde ein Hochregulation von PD-L1 und eine herunter Regulierung von HLA-DR auf Monozyten beobachtet. Dieser Phänotyp bestätigte die Konvertierung von klassischen Monozyten zu M-MDSCs. Die stimulierten Monozyten zeigten eine starke immunsuppressive Aktivität, da diese die Proliferation von CD8+ T Zellen, sowie deren Produktion von IFN-ү unterdrückten. Die Hochregulation von PD-L1 wurde über den Toll-like-Rezeptor (TLR)2 und TLR4 Signalweg induziert, wobei TLR4 eine dominantere Rolle spielte. Der Signalweg aktivierte NF-κB, was zur Hochregulation von PD-L1 führte. Die Blockade von TLR4 mittels TLR4-blockierenden Antikörpern, sowie NF-κB mit NF-κB Inhibitoren verringerte die PD-L1 Expression signifikant. Des Weiteren fanden wir, dass auf EVs von Melanomzelllinien HSP86 exprimiert wurde. Der Vergleich von HSP86+ EVs mit HSP86low/- EVs verdeutlichte die Bedeutung von der HSP86 vermittelten PD-L1 Expression und der immunsuppressiven Aktivität. Zudem haben wir die Expression von HSP86 in Plasma EVs von Melanompatienten getestet, welche eine Anti-PD-1 Therapie erhielten. Wir haben gezeigt, dass EVs von Nicht-Respondern die PD-L1 Expression hochregulierten und eine immunsuppressive Aktivität in zirkulierenden Monozyten induzierten. Diese EVs zeigten zusätzlich eine deutlich höhere Expression von HSP86 im Vergleich zu EVs von Respondern. Schließlich untersuchten wir PBMCs von 30 Melanompatienten vor und nach einer Anti-PD-1 Behandlung. Wir fanden eine signifikante Abnahme der PD-L1-Expression in zirkulierenden Monozyten von Respondern im Vergleich zum Status beim Beginn der Therapie. Darüber hinaus zeigten Patienten mit niedrigerer PD-L1 Expression auf zirkulierenden Monozyten besseres progressionsfreies Überleben. Zusammengefasst demonstrieren unsere Ergebnisse eine bedeutende Rolle von Tumor-EVs bei der Umwandlung von zirkulierender Monozyten in M-MDSCs. Des Weiteren konnten wir zeigen, dass die PD-L1 Expression auf Monozyten bei Melanompatienten, welche sich einer Anti-PD-1 Therapie unterziehen, eine entscheidende Rolle bei der Vorhersage des Therapieerfolgs hat
R&D modes and firm performance in high-tech companies: A research based on cross-boundary ambidexterity and network structures
This paper draws on the cross-boundary ambidexterity theory to propose that four different R&D modes impact firm performance differently and that cooperative network structure moderates the above relationships. The theoretical model is tested by using financial and patent data of 587 high-tech firms for 10 consecutive years in China. We find that different R&D modes have different impacts on a firm’s financial and innovative performance, and network structure plays different moderating roles. Practically, this work guides high-tech enterprises to optimize their resource allocation, select the most appropriate R&D mode, and establish efficient cooperative networks
An Augmented Subspace Based Adaptive Proper Orthogonal Decomposition Method for Time Dependent Partial Differential Equations
In this paper, we propose an augmented subspace based adaptive proper
orthogonal decomposition (POD) method for solving the time dependent partial
differential equations. By augmenting the POD subspace with some auxiliary
modes, we obtain an augmented subspace. We use the difference between the
approximation obtained in this augmented subspace and that obtained in the
original POD subspace to construct an error indicator, by which we obtain a
general framework for augmented subspace based adaptive POD method. We then
provide two strategies to obtain some specific augmented subspaces, the random
vector based augmented subspace and the coarse-grid approximations based
augmented subspace. We apply our new method to two typical 3D
advection-diffusion equations with the advection being the Kolmogorov flow and
the ABC flow. Numerical results show that our method is more efficient than the
existing adaptive POD methods, especially for the advection dominated models.Comment: 28 pages, 4 figures, 7 table
Synapse: Interactive Guidance by Demonstration with Trial-and-Error Support for Older Adults to Use Smartphone Apps
As smartphones are widely adopted, mobile applications (apps) are emerging to
provide critical services such as food delivery and telemedicine. While bring
convenience to everyday life, this trend may create barriers for older adults
who tend to be less tech-savvy than young people. In-person or screen sharing
support is helpful but limited by the help-givers' availability. Video
tutorials can be useful but require users to switch contexts between watching
the tutorial and performing the corresponding actions in the app, which is
cumbersome to do on a mobile phone. Although interactive tutorials have been
shown to be promising, none was designed for older adults. Furthermore, the
trial-and-error approach has been shown to be beneficial for older adults, but
they often lack support to use the approach. Inspired by both interactive
tutorials and trial-and-error approach, we designed an app-independent mobile
service, \textit{Synapse}, for help-givers to create a multimodal interactive
tutorial on a smartphone and for help-receivers (e.g., older adults) to receive
interactive guidance with trial-and-error support when they work on the same
task. We conducted a user study with 18 older adults who were 60 and over. Our
quantitative and qualitative results show that Synapse provided better support
than the traditional video approach and enabled participants to feel more
confident and motivated. Lastly, we present further design considerations to
better support older adults with trial-and-error on smartphones
Cognitive Flexibility and Advice Network Centrality: The Moderating Role of Self-Monitoring
This study examined the role of individuals’ cognitive flexibility and self-monitoring in shaping their workplace advice network centrality. Drawing on advice network generation theory, we hypothesized a positive relationship between cognitive flexibility and advice network centrality, and a moderation effect of self-monitoring on this relationship. Then, we collected two time-points data from insurance salesmen to test the hypotheses. As predicted, cognitive flexibility was positively associated with advice network centrality. Furthermore, this positive relationship was only significant for low self-monitoring individuals, but not for high self-monitoring individuals. These findings indicated that individuals with high cognitive flexibility were more likely to have central positions in the advice network; however, this effect was attenuated as their self-monitoring increased
Boosting output performance of contact-separation mode triboelectric nanogenerators by adopting discontinuity and fringing effect: experiment and modelling studies
Triboelectric nanogenerators (TENGs) are promising self-powering supplies for
a diverse range of intelligent sensing and monitoring devices, especially due
to their capability of harvesting electric energy from low frequency and
small-scale mechanical motions. Inspired by the fact that contact-separation
mode TENGs with small contact areas harvest high electrical outputs due to
fringing effect, this study employed discontinuity on the dielectric side of
contact-separation mode TENGs to promote fringing electric fields for the
enhancement of electrical outputs. The results reveal that the TENGs with more
discontinuities show higher overall electric performance. Compared to pristine
TENGs, the TENGs with cross discontinuities increased the surface charge by 50%
and the power density by 114%. However, one should avoid generating
discontinuities on tribonegative side of TENGs using metal blade within a
positive-ion atmosphere due to the neutralization through electrically
conductive metal blade. The computational simulation validated that the TENGs
with discontinuities obtained higher electrical outputs, and further
investigated the effect of discontinuity gap size and array distance on TENGs
performance. This study has provided a promising method for the future design
of TENGs using discontinuous structures.Comment: 23 pages, 8 figure
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