ABSTRACT
Heat dissipation threatens the performance and lifetime of many electronic devices. As the size of devices shrinks to the nanoscale, we require spatially and thermally resolved thermometry to observe their fine thermal features. Scanning thermal microscopy (SThM) has proven to be a versatile measurement tool for characterizing the temperature at the surface of devices with nanoscale resolution. SThM can obtain qualitative thermal maps of a device using an operating principle based on a heat exchange process between a thermo-sensitive probe and the sample surface. However, the quantification of these thermal features is one of the most challenging parts of this technique. Developing reliable calibration approaches for SThM is therefore an essential aspect to accurately determine the temperature at the surface of a sample or device. In this work, we calibrate a thermo-resistive SThM probe using heater-thermometer metal lines with different widths (50 nm to 750 nm), which mimic variable probe-sample thermal exchange processes. The sensitivity of the SThM probe when scanning the metal lines is also evaluated under different probe and line temperatures. Our results reveal that the calibration factor depends on the probe measuring conditions and on the size of the surface heating features. This approach is validated by mapping the temperature profile of a phase change electronic device. Our analysis provides new insights on how to convert the thermo-resistive SThM probe signal to the scanned device temperature more accurately.
ABSTRACT
Adoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been successfully utilized to treat graft versus host disease and represents a promising strategy for the treatment of autoimmune diseases and transplant rejection. The aim of this study was to evaluate the effects of all-trans retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. Naive T cells were polyclonally stimulated and cultured for five days in the presence of different combinations of IL-2, TGF-ß1, atRA and RAPA. The resulting cells were characterized by the expression of FOXP3, activation, surface and homing markers. Methylation of the Conserved Non-coding Sequence 2 was also evaluated. Functional comparison of the different culture conditions was performed by suppression assays in vitro. Culturing naive human T cells with IL-2/TGFß1 resulted in the generation of 54.2% of Treg cells (CD4+CD25+FOXP3+) whereas the addition of 100 nM atRA increased the yield of Treg cells to 66% (p = 0.0088). The addition of RAPA did not increase the number of Treg cells in any of these settings. Treg cells generated in the presence of atRA had an increased expression of the ß7 integrin to nearly 100% of the generated Treg cells, while RAPA treated cells showed enhanced expression of CXCR4. The differential expression of homing molecules highlights the possibility of inducing Treg cells with differential organ-specific homing properties. Neither atRA nor RAPA had an effect on the highly methylated CNS2 sites, supporting reports that their contribution to the lineage stability of Treg cells is not mediated by methylation changes in this locus. Treg cells generated in the presence of RAPA show the most potent suppression effect on the proliferation of effector cells.
