Finite element analysis of yield functions of Kelvin foams with open cells

Thesis (M.S.) University of Alaska Fairbanks, 2001Proper design of foams requires an understanding of the response of the materials to stress. This thesis, based on finite element analysis, provides numerical solutions in modeling the yield behavior of Kelvin foams. The FEA model, representing a complicated unit cell, was calculated and meshed. C++ programs were designed and implemented to generate meshes for unit cells. Finite element analyses were performed for many cases. Multiple methods were employed for the determination of yield points which form yield surfaces. Comparisons between several results have been made. Our FEA results, Zhang's function and Gibson's theory show good agreements except some differences under hydrostatic loading. A conclusion can be made: besides the void fraction and the yield strength of the wall material, the structure of foams also has a significant effect on the yield behavior of foams. Yield surfaces normalized by the uniaxial tensile strength of foams are more reasonable

KNOWLEDGE FLOW AND VALUE CREATION: INTEGRATING STRUCTURAL EMBEDDEDNESS AND KNOWLEDGE EMBEDDEDNESS IN ALLIANCE NETWORKS

Scholars in a variety of disciplines, including organizational theory, strategic management, and economics, have devoted substantial attention to the question: why are some firms more innovative than others? It has been largely accepted that when the knowledge base of an industry is both complex and expanding and the sources of expertise are widely dispersed, the locus of innovation will be found in networks of inter-organizational collaborations than individual firms. Strategy researchers have recently begun to explore how inter-firm networking affects organizational innovation performance, and reported intriguing yet conflicting findings. Drawing perspectives from strategic alliance, social networks, and technology innovation, I proposed an integrative framework to investigate the combined effects of a firm's network centrality and structural hole on organizational innovation performance. Furthermore, I examine the innovation performance both in terms of innovation rate and innovation value. I conducted a longitudinal study on a population of firms from 1990 to 1999 in pharmaceutical industry (SIC 2834). The results of the study indicate that: 1) Network centrality helps a firm to increase its rate of innovation, and structural hole helps to improve its value of innovation, while both effects are non-linear. 2) Network centrality positively moderates the relationship between structural hole and innovation value. 3) Structural hole negatively moderates the effect of network centrality on innovation rate. The joint effects suggest that firms with advantageous network positions are more capable of making wise technology selections and focusing their efforts on innovations of greater value

The Role of Glutaminase and Extracellular Vesicles in Macrophages and Microglia

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune activation. The GLS-containing EVs induce neurotoxicity through the overproduction of glutamate, implicating the pathogenic role of EVs and GLS1 in HAND. Regulation of EV remains to be fully elucidated in HAND. Interestingly, when carried as cargo, GLS1 showed a potential effect on the release of EV. Therefore, we hypothesize that the release of EV is dependent on GLS1-mediated glutamine and sphingolipid metabolism. In chapter III, we investigated the involvement of GLS1 in EV release in GLS1-overexpressing HeLa cells, HIV-1-infected macrophages, and immune-activated microglia through the use of GLS1 inhibitors. In the aforementioned cell types, GLS1 inhibitor significantly decreased the level of EVs, suggesting an important role of GLS1 in EV regulation. In chapter IV, we further investigated the mechanism of GLS1-mediated EV release. We identified that GLS1-mediated EV release is dependent upon the level of glutamine and α-ketoglutarate (α-KG). Because α-KG is an important metabolite of glutamate, these data suggest that α-KG is an essential GLS1 downstream factor that regulates the release of EVs. Biogenesis of EVs requires the sphingolipid ceramide. However, it is unknown whether GLS1-mediated EV release involves ceramide. We have demonstrated that the addition of ceramide rescued the suppression of EV release by GLS1 inhibitors, suggesting that GLS1 mediates EV release through ceramide. In summary, our data revealed two interesting insights into the biology of EVs. First, GLS-containing EVs is a pathogenic component of neurodegeneration in HAND. Second, the release of EVs is dependent on GLS1-mediated glutamine and sphingolipid metabolism. Studies on both of these aspects in EVs could lead to potential novel therapeutic targets for HAND and other neurodegenerative diseases

Molecular and cellular studies of zoledronic acid : a potent inhibitor of multiple myeloma-induced osteolysis

Myelomatosis (MM) is an incurable B cell malignancy, characterised by the presence of osteolytic bone lesions, a major cause of morbidity and mortality. This study investigated the effect of zoledronic acid, a potent nitrogen-containing bisphosphonate (BP), on myeloma cells and osteoblasts-like cells to establish the molecular and cellular mechanism responsible for the clinical effectiveness of BPs in the treatment of patients with MM. These studies indicate that zoledronic acid induces apoptotic and non-apoptotic cell death in myeloma cell lines bV (1) inducing S phase arrest in a time and dose dependent manner, (2) inhibiting the mevalonate pathway, and (3) up regulating TRAIL expression and uncoupling the regulated expression of TRAIL death and decoy receptors. Using an established model of osteoblast differentiation, zoledronic acid was found to increase the number of mature osteoblast/osteocyte-like cells, with a concomitant decrease in the number of stromal precursor cells. In accordance with these findings, zoledronic acid was found to enhance the osteoblast-like cells' ability to form a mineralised bone matrix, when used at concentrations in the range of 5pM and 25 pM. Therefore, we conclude that zoledronic acid mediates the differentiation of osteoblasts-like cells, which accounts for the enhanced bone formation. Zoledronic acid also upregulates the gene expression of IL-l8 and TNF-cr, which serve to increase the number of osteoprogenitors cells which in tum can respond to zoledronic acid. Furthermore, zoledronic acid was found to decrease the expression of membrane-associated RANKL by increasing TACE expression, a metalloproteinase disintegrin. In conclusion, the studies presented herein show that zoledronic acid enhances bone formation by directly acling on osteoblasts. In conclusion, work reported in this thesis suggests that myeloma cell death, and proliferation and maturation of osteoblasts represent two mechanisms that zoledronic acid inhibits MMinduced ostolysis.Thesis (M.Med.Sc.)-- University of Adelaide, Dept. of Medicine, 200

Statistical Analysis of MOBVE Distribution with TFR Model Under Step-Stress Accelerated Life Test

We obtain the maximum likelihood estimates of parameters of MOBVE distribution with tampered failure rate model under step-stress accelerated life test. Thereafter we show the feasibility of this method by using the Monte-Carlo simulation

Tactile-like corpuscles in gastric mucosa: a case report

BACKGROUND: The presence of tactile corpuscle-like structures in Schwannomas, Neurofibromas and Neuroid Intradermal Melanocytic Nevi is well-documented. We report a case describing the presence of such structures in the lamina propria of grossly normal gastric mucosa. CASE PRESENTATION: A 30 year-old male underwent esophagogastrectomy for carcinoma. Examination of hematoxylin and eosin stained sections reveal tactile corpuscle-like structures in the mucosa adjacent to the main tumor mass. CONCLUSION: This is a rare phenomenon and a literature search revealed only one paper describing such structures in the benign colonic mucosa of a colectomy done for carcinoma. We did not come across any cases in the literature describing such structures in gastrointestinal specimen resected for reasons other than carcinoma. To our knowledge this would be the first case reporting the existence of tactile corpuscles-like structures in gastric mucosa

The Statistical Analysis of a Certain Kind of Sales Diffusion Model

The essay works out MLE (Maximum Likelihood Estimation) of probability model parameter about the third sales diffusion curve given by ZHENG Zukang and researches the existence of the estimation. Besides, this essay inspects the accuracy of the estimation via Monte Carlo simulation and throws light on methods of essay by simulated data.Key words: Sales diffusion model; Maximum Likelihood Estimation; Monte Carlo simulatio

Serial deletion reveals structural basis and stability for the core enzyme activity of human glutaminase 1 isoforms: relevance to excitotoxic neurodegeneration.

BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence. We have previously identified that KGA and GAC are differentially regulated during inflammatory stimulation and HIV infection. Furthermore, glutaminase 1 has been linked to brain diseases such as amyotrophic lateral sclerosis, Alzheimer\u27s disease, and hepatic encephalopathy. Core enzyme structure of KGA and GAC has been published recently. However, how other coding sequences affect their functional enzyme activity remains unclear. METHODS: We cloned and performed serial deletions of human full-length KGA and GAC from the N-terminal and the C-terminal at an interval of approximately 100 amino acids (AAs). Prokaryotic expressions of the mutant glutaminase 1 protein and a glutaminase enzyme activity assay were used to determine if KGA and GAC have similar efficiency and efficacy to convert glutamine into glutamate. RESULTS: When 110 AAs or 218 AAs were deleted from the N-terminal or when the unique portions of KGA and GAC that are beyond the 550 AA were deleted from the C-terminal, KGA and GAC retained enzyme activity comparable to the full length proteins. In contrast, deletion of 310 AAs or more from N-terminal or deletion of 450 AAs or more from C-terminal resulted in complete loss of enzyme activity for KGA/GAC. Consistently, when both N- and C-terminal of the KGA and GAC were removed, creating a truncated protein that expressed the central 219 AA - 550 AA, the protein retained enzyme activity. Furthermore, expression of the core 219 AA - 550 AA coding sequence in cells increased extracellular glutamate concentrations to levels comparable to those of full-length KGA and GAC expressions, suggesting that the core enzyme activity of the protein lies within the central 219 AA - 550 AA. Full-length KGA and GAC retained enzyme activities when kept at 4 °C. In contrast, 219 AA - 550 AA truncated protein lost glutaminase activities more readily compared with full-length KGA and GAC, suggesting that the N-terminal and C-terminal coding regions are required for the stability KGA and GAC. CONCLUSIONS: Glutaminase isoforms KGA and GAC have similar efficacy to catalyze the conversion of glutamine to glutamate. The core enzyme activity of glutaminase 1 protein is within the central 219 AA - 550 AA. The N-terminal and C-terminal coding regions of KGA and GAC help maintain the long-term activities of the enzymes

CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment