On General Axial Gauges for QCD

General Axial Gauges within a perturbative approach to QCD are plagued by 'spurious' propagator singularities. Their regularisation has to face major conceptual and technical problems. We show that this obstacle is naturally absent within a Wilsonian or 'Exact' Renormalisation Group approach and explain why this is so. The axial gauge turns out to be a fixed point under the flow, and the universal 1-loop running of the gauge coupling is computed.Comment: 4 pages, latex, talk presented by DFL at QCD'98, Montpellier, July 2-8, 1998; to be published in Nucl. Phys. B (Proc. Suppl.

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.

Molecular characterization of transforming growth factor-beta3

Normal tissue homeostasis is controlled by a critical balance of positive and negative modulators. Chapter 2 gives an overview of the molecular aspects of growth control, in particular the role of growth factors and oncogene and anti-oncogene products. Uncontrolled growth of cancer cells may result from either an abrogation of growth stimulatory or a deficiency of growth inhibitory pathways. Mediators of growth inhibition include secretory polypeptide growth inhibitors, like transforming growth factor β(TGF-β) and nuclear proteins, like the retinoblastoma gene product. Early studies on organogenesis suggested the presence of growth inhibitors (challones) to regulate the growth of organs. Postulating that growth inhibitory proteins might have potential in cancer therapy, we began to analyze human tissues for the presence of novel tumor inhibitory factors. Purification of these activities and physico-chemical characterization suggested a relatedness to TGF-β. The biochemistry and cell biology of (TGF-β) will be reviewed in Chapter 3.At the start of the investigation, only one (TGF-β) had been identified. Our subsequent results indicated that a family of TGF-βproteins exists. Conventional purification of these TGF-βlike activities provided only limited quantities of material for analysis. We therefore adopted an alternative strategy which included the isolation of the cDNAs for TGF-β-like factors using TGF-β1 as a probe, assuming that related molecules might possess sufficient sequence similarity to cross-hybridize to a TGF-β1 probe. Differential hybridization of a Southern blot with human genomic DNA probed with TGF-β1 cDNA suggested the presence of a related gene, which we termed TGF-β3. The research described in this thesis includes the molecular cloning and expression of TGF-β3. Furthermore, experiments were carried out to gain insight into the effects of TGF-β3 on cell growth and differentiation and its mechanism of action, including initial studies to gauge the potential therapeutic uses of this factor.In Chapter 4, we report the cloning of the human TGF-β3 cDNA and the encoded TGF-β3 protein is compared with other members of the TGF-βfamily. In Chapter 5 the interspecies conservation of TGF-B3 is examined and the chromosomal location of the human TGF-β3 gone is determined. In Chapter 6, the recombinant expression and purification of TGF-β3 is described. The purified TGF-β3 protein has potent growth modulating effects on a number of normal as well as tumor cells. The studies in Chapter 7 were performed to assess the effect of TGF-β3 on osteoblasts and to characterize the specific binding of TGF-β3 to bone cells. TGF-β3 appears to be a potent regulator of functions associated with bone formation. Crosslinking studies showed that TGF-β3 and TGF-β1 associate in a similar fashion with three cell surface binding proteins, which have been characterized as putative receptor types I and II and a membrane-bound proteoglycan, termed betaglycan. The different (TGF-β) isoforms appear to have different potencies on Mv1Lu mink lung epithelia] and fetal bovine heart endothelial cells. In Chapter 8, we investigate the role of TGF-β. receptors and serum factors as determinants of the cell-specific responsiveness to the three homodimeric isoforms. The induction of mesoderm in Xenopus laevis animal cap explants by TGF-β3 is discussed in Chapter 9. Finally, in Chapter 10 we review the therapeutic applications of growth factors for wound healing

Targeting TGF beta signal transduction for cancer therapy

Transforming growth factor-beta (TGF beta) family members are structurally and functionally related cytokines that have diverse effects on the regulation of cell fate during embryonic development and in the maintenance of adult tissue homeostasis. Dysregulation of TGF beta family signaling can lead to a plethora of developmental disorders and diseases, including cancer, immune dysfunction, and fibrosis. In this review, we focus on TGF beta, a well-characterized family member that has a dichotomous role in cancer progression, acting in early stages as a tumor suppressor and in late stages as a tumor promoter. The functions of TGF beta are not limited to the regulation of proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and metastasis of cancer cells. Recent reports have related TGF beta to effects on cells that are present in the tumor microenvironment through the stimulation of extracellular matrix deposition, promotion of angiogenesis, and suppression of the anti-tumor immune reaction. The pro-oncogenic roles of TGF beta have attracted considerable attention because their intervention provides a therapeutic approach for cancer patients. However, the critical function of TGF beta in maintaining tissue homeostasis makes targeting TGF beta a challenge. Here, we review the pleiotropic functions of TGF beta in cancer initiation and progression, summarize the recent clinical advancements regarding TGF beta signaling interventions for cancer treatment, and discuss the remaining challenges and opportunities related to targeting this pathway. We provide a perspective on synergistic therapies that combine anti-TGF beta therapy with cytotoxic chemotherapy, targeted therapy, radiotherapy, or immunotherapy.Cancer Signaling networks and Molecular Therapeutic

E3 ubiquitin ligases: key regulators of TGF beta signaling in cancer progression

Transforming growth factor beta (TGF beta) is a secreted growth and differentiation factor that influences vital cellular processes like proliferation, adhesion, motility, and apoptosis. Regulation of the TGF beta signaling pathway is of key importance to maintain tissue homeostasis. Perturbation of this signaling pathway has been implicated in a plethora of diseases, including cancer. The effect of TGF beta is dependent on cellular context, and TGF beta can perform both anti- and pro-oncogenic roles. TGF beta acts by binding to specific cell surface TGF beta type I and type II transmembrane receptors that are endowed with serine/threonine kinase activity. Upon ligand-induced receptor phosphorylation, SMAD proteins and other intracellular effectors become activated and mediate biological responses. The levels, localization, and function of TGF beta signaling mediators, regulators, and effectors are highly dynamic and regulated by a myriad of post-translational modifications. One such crucial modification is ubiquitination. The ubiquitin modification is also a mechanism by which crosstalk with other signaling pathways is achieved. Crucial effector components of the ubiquitination cascade include the very diverse family of E3 ubiquitin ligases. This review summarizes the diverse roles of E3 ligases that act on TGF beta receptor and intracellular signaling components. E3 ligases regulate TGF beta signaling both positively and negatively by regulating degradation of receptors and various signaling intermediates. We also highlight the function of E3 ligases in connection with TGF beta's dual role during tumorigenesis. We conclude with a perspective on the emerging possibility of defining E3 ligases as drug targets and how they may be used to selectively target TGF beta-induced pro-oncogenic responses.Cancer Signaling networks and Molecular Therapeutic

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Cancer Signaling networks and Molecular Therapeutic

Cancer associated-fibroblast-derived exosomes in cancer progression

To identify novel cancer therapies, the tumor microenvironment (TME) has received a lot of attention in recent years in particular with the advent of clinical successes achieved by targeting immune checkpoint inhibitors (ICIs). The TME consists of multiple cell types that are embedded in the extracellular matrix (ECM), including immune cells, endothelial cells and cancer associated fibroblasts (CAFs), which communicate with cancer cells and each other during tumor progression. CAFs are a dominant and heterogeneous cell type within the TME with a pivotal role in controlling cancer cell invasion and metastasis, immune evasion, angiogenesis and chemotherapy resistance. CAFs mediate their effects in part by remodeling the ECM and by secreting soluble factors and extracellular vesicles. Exosomes are a subtype of extracellular vesicles (EVs), which contain various biomolecules such as nucleic acids, lipids, and proteins. The biomolecules in exosomes can be transmitted from one to another cell, and thereby affect the behavior of the receiving cell. As exosomes are also present in circulation, their contents can also be explored as biomarkers for the diagnosis and prognosis of cancer patients. In this review, we concentrate on the role of CAFs-derived exosomes in the communication between CAFs and cancer cells and other cells of the TME. First, we introduce the multiple roles of CAFs in tumorigenesis. Thereafter, we discuss the ways CAFs communicate with cancer cells and interplay with other cells of the TME, and focus in particular on the role of exosomes. Then, we elaborate on the mechanisms by which CAFs-derived exosomes contribute to cancer progression, as well as and the clinical impact of exosomes. We conclude by discussing aspects of exosomes that deserve further investigation, including emerging insights into making treatment with immune checkpoint inhibitor blockade more efficient.Cancer Signaling networks and Molecular Therapeutic

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