Carbon nanotube thermal interfaces and related applications

The development of thermal interface materials (TIMs) is necessitated by the temperature drop across interfacing materials arising from macro and microscopic irregularities of their surfaces that constricts heat through small contact regions as well as mismatches in their thermal properties. Similar to other types of TIMs, CNT TIMs alleviate the thermal resistance across the interface by thermally bridging two materials together with cylindrical, high-aspect ratio, and nominally vertical conducting elements. Within the community of TIM engineers, the vision driving the development of CNT TIMs was born from measurements that revealed impressively high thermal conductivities of individual CNTs. This vision was then projected to efforts focused on packing many individual CNTs on a single substrate that efficiently conduct heat in parallel and ultimately through many contact regions at CNT-to-substrate contacts. This thesis encompasses a comprehensive investigation of the viability of carbon nanotube based thermal interface materials (CNT TIMs) to efficiently conduct heat across two contacting materials. The efforts in this work were initially devoted to engaging CNT TIMs with an opposing substrate using two bonding techniques. Using palladium hexadecanethiolate, Pd(SC16H35)2 the CNT ends were bonded to an opposing substrate (one-sided interface) or opposing CNT array (two-sided interface) to enhance contact conductance while maintaining a compliant joint. The palladium weld is particularly attractive for its mechanical stability at high temperatures. The engagement of CNT TIMs with an opposing substrate was also achieved by inserting a solder foil between the CNT TIM and opposing substrate and subsequently raising the temperature of the interface above the eutectic point of the solder foil. This bonding technique creates a strong weld that not only reduces the thermal resistance significantly but also minimizes the change in thermal resistance with an applied compressive load. The thermal performance was further improved by infiltrating the CNT TIM with paraffin wax, which serves as an alternate pathway for heat conduction across the interface that ultimately reduces the bulk thermal resistance of the CNT TIM. For CNT TIMs synthesized at the Birck Nanotechnology Center at Purdue University, the thermal resistance was shown to scale linearly with their aggregate, as-grown height. Thus, the bulk thermal resistance can alternatively be tuned by adjusting the as-grown height. The linear relationship between thermal resistance and CNT TIM height provides a simple and efficient methodology to estimate the contact resistance and effective thermal conductivity of CNT TIMs. In this work, the contact resistance and effective thermal conductivity were estimated using two measurement techniques: (i) one-dimensional, steady-state reference bar and (ii) photoacoustic technique. A discrepancy in the estimated contact resistance exists between the two measurement techniques, which is due to the difficulty in measuring the true contact area. In contrast, the effective thermal conductivities estimated from both measurement techniques moderately agreed and were estimated to be on the order of O(1 W/mK). The final chapter is in collaboration with Sandia National Laboratories and focuses on the development of an apparatus to measure the thermal conductivity of insulation materials critical for the operation of molten salt batteries. Molten salt batteries are particularly useful power sources for radar and guidance systems in military applications such as guided missiles, ordinance, and other weapons. Molten salt batteries are activated by raising the temperature of the electrolyte above its melting temperature using pyrotechnic heat pellets. The battery will remain active as long as the electrolyte is molten. As a result, the thermal processes within the components and interactions between them are critical to the overall performance of molten salt batteries. A molten salt battery is typically thermally insulated using wrappable and board-like insulation materials such as Fiberfrax wrap, Fiberfrax board, and Min-K insulation. The Fiberfrax board and Min-K insulation are composites of alumino-silicate and fumed silica-titania, respectively. In Chapter 9, the thermal conductivities of the Fiberfrax board and Min-K insulation were measured under different uniaxial compressive states and ambient environments. The thermal conductivity of the mixed separator pellets (LiCl/MgO/KCl) was also measured along with its contact resistances with interfacing members. To measure the thermal quantities, a steady-state reference bar with thermocouples was employed. The resulting values serve as inputs to a thermal model that aims to predict lifetimes of the batteries. (Abstract shortened by ProQuest.

Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression

Cancers may escape elimination by the host immune system by rewiring the tumour microenvironment towards an immune suppressive state. Transforming growth factor-β (TGF-β) is a secreted multifunctional cytokine that strongly regulates the activity of immune cells while, in parallel, can promote malignant features such as cancer cell invasion and migration, angiogenesis, and the emergence of cancer-associated fibroblasts. TGF-β is abundantly expressed in cancers and, most often, its abundance associated with poor clinical outcomes. Immunotherapeutic strategies, particularly T cell checkpoint blockade therapies, so far, only produce clinical benefit in a minority of cancer patients. The inhibition of TGF-β activity is a promising approach to increase the efficacy of T cell checkpoint blockade therapies. In this review, we briefly outline the immunoregulatory functions of TGF-β in physiological and malignant contexts. We then deliberate on how the therapeutic targeting of TGF-β may lead to a broadened applicability and success of state-of-the-art immunotherapies.Cancer Signaling networks and Molecular Therapeutic

Genomic characterization of the human DNA excision repair gene ERCC-1.

In this report the genomic characterization of the human excision repair gene ERCC-1 is presented. The gene consists of 10 exons spread over approximately 15 kb. By means of a transfection assay the ERCC-1 promoter was confined to a region of + 170 bp upstream of the transcriptional start site. Classical promoter elements like CAAT, TATA and GC-boxes are absent from this region. Furthermore, ERCC-1 transcription is not UV-inducible. A possible explanation is provided for the previously reported alternative splicing of exon VIII. Analysis of ERCC-1 cDNA clones revealed the occurrence of differential polyadenylation which gives ERCC-1 transcripts of 3.4 and 3.8 kb in addition to the major 1.1 kb mRNA. Apparent evolutionary conservation of differential polyadenylation of ERCC-1 transcripts suggests a possible role for this mode of RNA processing in the ERCC-1 repair function

Make me want to pay! A three-way interaction between procedural justice, distributive justice, and power on voluntary tax compliance

Tax compliance involves a decision where personal benefits come at the expense of society and its members. We explored the roles of procedural and distributive justice and citizens’ perceptions of the tax authority’s power in stimulating voluntary tax compliance. Distributive and procedural justice have often (but not always) been shown to interact in such a way that high distributive justice or high procedural justice is sufficient to predict positive responses to authorities and the social collective they represent. We examined whether this interaction predicts voluntary (but not enforced) tax compliance, in particular among citizens who perceive the tax authority’s power as high (vs. low). The results of two field studies among Ethiopian (Study 1) and United States (Study 2) taxpayers supported our pre

TGF-beta-mediated endothelial to mesenchymal transition (EndMT) and the functional assessment of EndMT effectors using CRISPR/Cas9 gene editing

In response to specific external cues and the activation of certain transcription factors, endothelial cells can differentiate into a mesenchymal-like phenotype, a process that is termed endothelial to mesenchymal transition (EndMT). Emerging results have suggested that EndMT is causally linked to multiple human diseases, such as fibrosis and cancer. In addition, endothelial-derived mesenchymal cells may be applied in tissue regeneration procedures, as they can be further differentiated into various cell types (e.g., osteoblasts and chondrocytes). Thus, the selective manipulation of EndMT may have clinical potential. Like epithelial-mesenchymal transition (EMT), EndMT can be strongly induced by the secreted cytokine transforming growth factor-beta (TGF-beta), which stimulates the expression of so-called EndMT transcription factors (EndMT-TFs), including Snail and Slug. These EndMT-TFs then up- and downregulate the levels of mesenchymal and endothelial proteins, respectively. Here, we describe methods to investigate TGF-beta-induced EndMT in vitro, including a protocol to study the role of particular TFs in TGF-beta-induced EndMT. Using these techniques, we provide evidence that TGF-beta 2 stimulates EndMT in murine pancreatic microvascular endothelial cells (MS-1 cells), and that the genetic depletion of Snail using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPRassociated protein 9 (Cas9)-mediated gene editing, abrogates this phenomenon. This approach may serve as a model to interrogate potential modulators of endothelial biology, and can be used to perform genetic or pharmacological screens in order to identify novel regulators of EndMT, with potential application in human disease.Cancer Signaling networks and Molecular Therapeutic

Willing and able: action-state orientation and the relation between procedural justice and employee cooperation

Existing justice theory explains why fair procedures motivate employees to adopt cooperative goals, but it fails to explain how employees strive towards these goals. We study self-regulatory abilities that underlie goal striving; abilities that should thus affect employees’ display of cooperative behavior in response to procedural justice. Building on action control theory, we argue that employees who display effective self-regulatory strategies (action oriented employees) display relatively strong cooperative behavioral responses to fair procedures. A multisource field study and a laboratory experiment support this prediction. A subsequent experiment addresses the process underlying this effect by explicitly showing that action orientation facilitates attainment of the cooperative goals that people adopt in response to fair procedures, thus facilitating the display of actual cooperative behavior. This goal striving approach better integrates research on the relationship between procedural justice and employee cooperation in the self-regulation and the work motivation literature. It also offers organizations a new perspective on making procedural justice effective in stimulating employee cooperation by suggesting factors that help employees reach their adopted goals

BMP-7 inhibits TGF-β-induced invasion of breast cancer cells through inhibition of integrin β3 expression

BACKGROUND The transforming growth factor (TGF)-β superfamily comprises cytokines such as TGF-β and Bone Morphogenetic Proteins (BMPs), which have a critical role in a multitude of biological processes. In breast cancer, high levels of TGF-β are associated with poor outcome, whereas inhibition of TGF-β-signaling reduces metastasis. In contrast, BMP-7 inhibits bone metastasis of breast cancer cells. METHODS In this study, we investigated the effect of BMP-7 on TGF-β-induced invasion in a 3 dimensional invasion assay. RESULTS BMP-7 inhibited TGF-β-induced invasion of the metastatic breast cancer cell line MCF10CA1a, but not of its premalignant precursor MCF10AT in a spheroid invasion model. The inhibitory effect appears to be specific for BMP-7, as its closest homolog, BMP-6, did not alter the invasion of MCF10CA1a spheroids. To elucidate the mechanism by which BMP-7 inhibits TGF-β-induced invasion, we analyzed invasion-related genes. BMP-7 inhibited TGF-β-induced expression of integrin α(v)β(3) in the spheroids. Moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin β(3) negatively affected TGF-β-induced invasion. On the other hand, overexpression of integrin β(3) counteracted the inhibitory effect of BMP7 on TGF-β-induced invasion. CONCLUSION Thus, BMP-7 may exert anti-invasive actions by inhibiting TGF-β-induced expression of integrin β(3).Prostatic carcinom

TGF-beta-induced endothelial to mesenchymal transition is determined by a balance between SNAIL and ID factors

Endothelial-to-mesenchymal transition (EndMT) plays an important role in embryonic development and disease progression. Yet, how different members of the transforming growth factor-beta (TGF-beta) family regulate EndMT is not well understood. In the current study, we report that TGF-beta 2, but not bone morphogenetic protein (BMP)9, triggers EndMT in murine endothelial MS-1 and 2H11 cells. TGF-beta 2 strongly upregulates the transcription factor SNAIL, and the depletion of Snail is sufficient to abrogate TGF-beta 2-triggered mesenchymal-like cell morphology acquisition and EndMT-related molecular changes. Although SLUG is not regulated by TGF-beta 2, knocking out Slug also partly inhibits TGF-beta 2-induced EndMT in 2H11 cells. Interestingly, in addition to SNAIL and SLUG, BMP9 stimulates inhibitor of DNA binding (ID) proteins. The suppression of Id1, Id2, or Id3 expression facilitated BMP9 in inducing EndMT and, in contrast, ectopic expression of ID1, ID2, or ID3 abrogated TGF-beta 2-mediated EndMT. Altogether, our results show that SNAIL is critical and indispensable for TGF-beta 2-mediated EndMT. Although SLUG is also involved in the EndMT process, it plays less of a crucial role in it. In contrast, ID proteins are essential for maintaining endothelial traits and repressing the function of SNAIL and SLUG during the EndMT process. These data suggest that the control over endothelial vs. mesenchymal cell states is determined, at least in part, by a balance between the expression of SNAIL/SLUG and ID proteins.Cancer Signaling networks and Molecular Therapeutic