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2013

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Computational Analysis Of A Bead On A Wire, Kristofer William Schobert Dec 2013

Computational Analysis Of A Bead On A Wire, Kristofer William Schobert

Physics

No abstract provided.


The Imperative Of Conserving California's Foothill Oak Woodlands, Lauren Phillips Dec 2013

The Imperative Of Conserving California's Foothill Oak Woodlands, Lauren Phillips

Social Sciences

No abstract provided.


Pedagogical Development Of Zen Buddhism And Taoism For Taos Ed. Ventures, Kelsey Tyler Dec 2013

Pedagogical Development Of Zen Buddhism And Taoism For Taos Ed. Ventures, Kelsey Tyler

Social Sciences

Taos Ed. Ventures is an outdoor guiding company that will be offering backpacking trips in Taos, New Mexico to high school and college students, with ages ranging from 16 – 29, starting the summer of 2015. Along with backpacking skills, the philosophies of Zen Buddhism and Taoism will be taught while on the trail. To teach these philosophies, a pedagogy was created, combining aspects of Sentipensante and Contemplative pedagogies that seeks to teach the daily applications of Zen Buddhism and Taoism through experiential and innovative learning methods, such as journaling, meditation, and mindfulness practices. The benefits of these alternative learning …


Distribution Of Seaside Sparrows (Ammodramus Maritimus) During The Breeding And Nonbreeding Seasons, Bonnie J. Slaton Dec 2013

Distribution Of Seaside Sparrows (Ammodramus Maritimus) During The Breeding And Nonbreeding Seasons, Bonnie J. Slaton

Honors Capstones

No abstract provided.


The Manufacturing Sector In The Greater Northeastern/Northern Region Of Pennsylvania, Ziona Austrian, Candi Clouse, Merissa Piazza, Nikki Glazer, Eunkyu Lee, Hyejin Jung, Eric Esoda Dec 2013

The Manufacturing Sector In The Greater Northeastern/Northern Region Of Pennsylvania, Ziona Austrian, Candi Clouse, Merissa Piazza, Nikki Glazer, Eunkyu Lee, Hyejin Jung, Eric Esoda

All Maxine Goodman Levin School of Urban Affairs Publications

This report summarizes the findings of an in-depth study of the manufacturing sector in the Greater Northeastern/Northern region of Pennsylvania. The objective of the first section is to draw attention to the role manufacturing plays in the regional economy. It compares manufacturing to other sectors of the economy in terms of employment, gross regional product, wages, productivity, and number of establishments (See Table E-1). It also briefly describes trends in the value of shipments of manufacturing goods as a proxy for exports, manufacturers’ investments in capital expenditures as a measure of capital intensity and adoption of technology, and patenting activity …


Novel Functions Of Cetuximab In Egfr-Targeted Therapy: Radiosensitization, Glycolysis Inhibition, And Cellular Redox Status Regulation, Haiquan Lu Dec 2013

Novel Functions Of Cetuximab In Egfr-Targeted Therapy: Radiosensitization, Glycolysis Inhibition, And Cellular Redox Status Regulation, Haiquan Lu

Dissertations and Theses (Open Access)

Epidermal growth factor receptor (EGFR) is overexpressed in the majority of head and neck cancers. The anti-EGFR antibody cetuximab has been approved by the FDA for the treatment of head and neck cancers, however, only a small fraction of patients respond to cetuximab treatment. Further investigation to understand the mechanisms underlying cetuximab-mediated EGFR-targeted therapy and to develop novel therapeutic strategies to improve the efficacy of cetuximab is urgently needed. In the present study, we elucidated the mechanism of cetuximab in radiosensitization, and discovered novel functions of cetuximab in glycolysis inhibition and cellular redox status regulation. We found that cetuximab inhibits …


Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff Dec 2013

Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff

Dissertations and Theses (Open Access)

Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been …


Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz Dec 2013

Developmental And Molecular Functions Of Plakophilin-3, William A. Munoz

Dissertations and Theses (Open Access)

Plakophilin-3, the less studied member of the plakophilin-catenin subfamily, and the larger catenin family, binds directly to desmosomal cadherin cytoplasmic domains and enhances desmosome formation and stability. In mammals, plakophilin-3 is expressed at the highest levels in desmosome-enriched tissues such as epithelia, with the knock-out in mice producing corresponding reductions in ectodermal integrity. In tissue, cellular and intracellular contexts where plakophilin-3 is not at the desmosomal plaque, little is known about its functions in the cytoplasm or nucleus, where it also localizes.

My work employed embryos of the amphibian, Xenopus laevis, to examine plakophilin-3’s developmental roles. I first evaluated …


The Role And Mechanism Of The Homeobox Gene Hoxa9 In The Growth Of Epithelial Ovarian Cancer, Song Yi Ko Dec 2013

The Role And Mechanism Of The Homeobox Gene Hoxa9 In The Growth Of Epithelial Ovarian Cancer, Song Yi Ko

Dissertations and Theses (Open Access)

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer death among women in the United States. The high lethality of EOCs stems from rapid peritoneal involvement. EOCs frequently colonize peritoneal surfaces that overlie connective and adipose tissues. However, the mechanisms that enable ovarian cancer cells to readily adapt to the peritoneal environment are poorly understood. HOXA9, a homeobox gene that is normally expressed in the developing female reproductive tract, is aberrantly expressed in EOCs and controls the morphologic features of these tumors. The differentiation pattern of a tumor is an important determinant of its clinical behavior and …


Therapeutic Efficacy Of P53 Restoration In Mdm2-Overexpressing Tumors, Qin Li Dec 2013

Therapeutic Efficacy Of P53 Restoration In Mdm2-Overexpressing Tumors, Qin Li

Dissertations and Theses (Open Access)

The TP53 tumor suppressor is the most mutated gene in human cancers. Recent studies using genetically modified mouse models have shown that restoring the expression of wild-type p53 has led to tumor growth suppression in various types of tumors lacking p53. Other mechanisms, e.g. upregulation of Mdm2 levels, exist in tumors to inactivate the p53 pathway. Mdm2, an E3 ubiquitin-ligase that targets p53 for proteasomal degradation, is present at high levels in many tumors with wild-type p53. In this study, we probed the effects of restoring p53 activity in Mdm2-overexpressing tumors genetically using animal models. Here we demonstrated high levels …


Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin Dec 2013

Mtorc1 Signaling In Memory Formation And Dysfunction, Natalia S. Rozas De O'Laughlin

Dissertations and Theses (Open Access)

The mechanistic Target of Rapamycin Complex 1 (mTORC1) pathway integrates cellular availability of growth factors, energy and amino acids to regulate protein synthesis and autophagy. The mTORC1 pathway has also been shown to be required for memory consolidation, and its dysregulation is associated with many neurological disorders. MTORC1 is negatively regulated by the tuberous sclerosis complex (TSC1/2). When ATP and growth factors are available, TSC1/2 is inhibited and mTORC1 activity can be restored. In a complementary regulatory pathway, amino acids signal to mTORC1 through the Rag GTPases and Ragulator complex, which modulate the translocation of mTORC1 from the cytoplasm to …


Characterization Of The Role(S) Of Env Protein Of Human Endogenous Retrovirus-K In Multiple Human Cancers, Ming Li Dec 2013

Characterization Of The Role(S) Of Env Protein Of Human Endogenous Retrovirus-K In Multiple Human Cancers, Ming Li

Dissertations and Theses (Open Access)

Human endogenous retroviruses (HERVs) are remnants from ancient retroviral infections, and most of them are inactive in normal tissues. One family of HERV, HERV-K, is found to be associated with multiple human cancers including breast cancer, pancreatic cancer and melanoma, but the causal relationship between HERV-K and cancer is still unclear. Increased expression of HERV-K in melanoma cells correlates with malignant transformation, while a serological response to HERV-K in breast cancer or melanoma patients correlates with survival probability. However, the mechanism behind these observations remains obscure. Our laboratory reported that anti-HERV-K envelope (Env) protein antibodies show antitumor potential in targeting …


The Staphylococcus Pseudintermedius Adhesin Spsd Contains A Central Fibronectin-Binding Domain, Andrea S. Bordt Dec 2013

The Staphylococcus Pseudintermedius Adhesin Spsd Contains A Central Fibronectin-Binding Domain, Andrea S. Bordt

Dissertations and Theses (Open Access)

Staphylococcus pseudintermedius is a Gram-positive bacterium significant because of its ability to cause costly and difficult to treat veterinary infections worldwide. It exhibits several similarities to Staphylococcus aureus, however, very little is known about its surface adhesins. Surface adhesins in S. aureus are significant contributors to pathogenesis. S. pseudintermedius encodes the surface protein SpsD, which contains characteristics of the microbial surface components recognizing adhesive matrix molecules family and confers attachment of the heterologous host Lactococcus lactis to fibronectin. This work has identified a centrally-located fibronectin binding domain in SpsD which binds the 30 kDa N-terminal domain of fibronectin with …


Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang Dec 2013

Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang

Dissertations and Theses (Open Access)

Targeted therapy and immunotherapy eradicate malignant cells through different mechanisms, and the strengths and weaknesses of these two approaches are potentially complementary. Therefore, the combination of molecular targeted drugs with immune- based therapies is considered an attractive approach for improving the therapeutic efficacy of cancer treatment. The mutation and amplification of the c-KIT proto- oncogene are associated with multiple different cancer types, and multiple c-KIT inhibitors have been tested clinically. In spite of some encouraging results using these agents, most patients with c-KIT mutant cancers still relapse due to drug resistance. This also demonstrates the inherent limitation of molecular targeted …


Ventral Tegmental Area Neuronal Responses To Methylphenidate Correlated To Behavioral Responses Of Adolescent And Adult Rats, Zachary Jones Dec 2013

Ventral Tegmental Area Neuronal Responses To Methylphenidate Correlated To Behavioral Responses Of Adolescent And Adult Rats, Zachary Jones

Dissertations and Theses (Open Access)

Methylphenidate (MPD) is a psychostimulant used in the treat treatment of attention deficit hyperactivity disorder and more recently is being used as a cognitive enhancement and recreational drug. Its therapeutic effects are not fully understood, nor are the long term effects of the drug on brain development. The ventral tegmental area (VTA) is a site of psychostimulant action thought to be involved in behavioral sensitization. The aim of the this study was to first determine if there are differences in neuronal responses between individuals, with respect to neuronal firing patterns in the ventral tegmental area (VTA), and whether these differences …


C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein Dec 2013

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy. Moreover, …


Basis For Targeting Met Activation Mediated Resistance To Pi3k Inhibition In Breast Cancer, Ana M. Gonzalez-Angulo Dec 2013

Basis For Targeting Met Activation Mediated Resistance To Pi3k Inhibition In Breast Cancer, Ana M. Gonzalez-Angulo

Dissertations and Theses (Open Access)

The identification of resistance mechanisms to emerging therapies, such as those targeting the PI3K pathway and the MET receptor, has the potential to benefit a significant number of patients with breast cancer. In this study we hypothesized that concurrent aberrations in PI3K and MET will render breast cancers resistant to therapies targeting each pathway, and that combination therapy targeting the PI3K and MET pathway will optimize therapy-effect by preventing the acquisition of resistance.

We analyzed cMET and phospho-cMET levels in 257 breast cancer samples and found that high levels of both the proteins were seen in all breast cancer subtypes, …


Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum Dec 2013

Neural Correlates Of Audiovisual Speech Perception In Aphasia And Healthy Aging, Sarah H. Baum

Dissertations and Theses (Open Access)

Understanding speech in face-to-face conversation utilizes the integration of multiple pieces of information, most importantly the auditory vocal sounds and visual lip movements. Prior studies of the neural underpinnings of audiovisual integration in the brain have provided converging evidence to suggest that neurons within the left superior temporal sulcus (STS) provide a critical neural hub for the integration of auditory and visual information in speech. While most studies of audiovisual processing focus on neural mechanisms within healthy, young adults, we currently know very little about how changes to the brain can affect audiovisual integration in speech. To examine this further, …


Regulation Of The Myostatin Protein In Overload-Induced Hypertrophied Rat Skeletal Muscle, Paige Abriel Affleck Dec 2013

Regulation Of The Myostatin Protein In Overload-Induced Hypertrophied Rat Skeletal Muscle, Paige Abriel Affleck

Theses and Dissertations

Myostatin (GDF-8) is the chief chalone in skeletal muscle and negatively controls adult skeletal muscle growth. The role of myostatin during overload-induced hypertrophy of adult muscle is unclear. We tested the hypothesis that overloaded adult rodent skeletal muscle would result in reduced myostatin protein levels. Overload-induced hypertrophy was accomplished by unilateral tenotomy of the gastrocnemius tendon in male adult Sprague-Dawley rats followed by a two-week period of compensatory overload of the plantaris and soleus muscles. Western blot analysis was performed to evaluate changes in active, latent and precursor myostatin protein levels. Significant hypertrophy was noted in the plantaris (494 ± …


Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins Dec 2013

Association Between In Utero Arsenic Exposure, Placental Gene Expression, And Infant Birth Weight: A Us Birth Cohort Study, Dennis Liang Fei, Devin C. Koestler, Zhigang Li, Camilla Giambelli, Avencia Sanchez-Mejias, Julie Gosse, Carmen J. Marsit, Margaret R. Karagas, David J. Robbins

Dartmouth Scholarship

Epidemiologic studies and animal models suggest that in utero arsenic exposure affects fetal health, with a negative association between maternal arsenic ingestion and infant birth weight often observed. However, the molecular mechanisms for this association remain elusive. In the present study, we aimed to increase our understanding of the impact of low-dose arsenic exposure on fetal health by identifying possible arsenic-associated fetal tissue biomarkers in a cohort of pregnant women exposed to arsenic at low levels.

Methods: Arsenic concentrations were determined from the urine samples of a cohort of 133 pregnant women from New Hampshire. Placental tissue samples collected from …


Rendez Donc A Cesar, Problemes Avec Les Mots De Dieu: Land And The Civil Constitution Of The Clergy Of 1790-1791, Jonathan Monroe Dec 2013

Rendez Donc A Cesar, Problemes Avec Les Mots De Dieu: Land And The Civil Constitution Of The Clergy Of 1790-1791, Jonathan Monroe

All Theses

This study investigates the state's sale of Church lands and the Civil Constitution of the Clergy during the French Revolution. The Civil Constitution has been seen as a turning point in the era's progression; it created very sharp divisions in revolutionary ideals by forcing clergy members to take an oath to the state that was condemned by the pope. These divisions helped feed Jacobin extremism and an era of Christian suppression and the Terror eventually ensued. Despite these problems, the struggling country under the Old Regime was desperate for Church reform that the Civil Constitution provided. The prohibition of the …


Macroscopic Investigation Of Ionic- And Nano-Silver Toxicity To Soil Nitrification Process, Abdurrahman Masrahi Dec 2013

Macroscopic Investigation Of Ionic- And Nano-Silver Toxicity To Soil Nitrification Process, Abdurrahman Masrahi

All Theses

The worldwide production of engineered nanoparticles (ENPs) has grown rapidly in our era because of the popular applications in industrial and consumer markets. Especially silver (Ag) NP is one of mostly common ENPs in our consumer products due to its unique antimicrobial property. However, release of AgNPs into environment through wastewater treatment plants poses a question that what impact AgNPs have on microbially mediated processes in environment (e.g., nutrient and trace element cycles). In the last decades, numerous toxicological studies of AgNPs on bacteria have been conducted in pure culture systems, and several different antimicrobial mechanisms of AgNPs have been …


The Effect Of Cell Culture Environment On Expression Of Cd44+, Ki67, And Foxo3a And Its Implications On The Role Of Foxo3a In Triple Negative Breast Cancer, Erin Vegter Dec 2013

The Effect Of Cell Culture Environment On Expression Of Cd44+, Ki67, And Foxo3a And Its Implications On The Role Of Foxo3a In Triple Negative Breast Cancer, Erin Vegter

All Theses

Triple negative breast cancer (TNBC) is a highly aggressive cancer, which is known for a high rate of metastasis and poor prognosis. TNBC cells are hypothesized to undergo the cellular processes epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). The known prognostic markers CD44+ and Ki67 as well as the transcription factor and proposed tumor suppressor FoxO3a are thought to be indicators of EMT and MET activity in cancer cells. In order to better understand these processes an effective cell culture technique to mimic the tumor environment needs to be established. The purpose of this study was to determine if changing …


Remembering And The Everyday: The Fleeting, Fragmented, And Sensual, Alyssa Prince Dec 2013

Remembering And The Everyday: The Fleeting, Fragmented, And Sensual, Alyssa Prince

All Theses

Our memories are malleable. There is no identifiable truth; we consistently change them based on our present state of being. Nevertheless, our memories influence us greatly. My paintings engage this topic of the remembering process and display the active, reconstructive nature of how we remember. This idea is approached through making paintings that engage my own involuntary memories that are inevitably impossible to grasp. The resulting paintings explore issues pertaining to the remembering process, partiality, and the inaccuracies of representation. In this thesis, I discuss the importance of the reconstructed, provisional image, the fluctuating nature of our memories, an interaction …


Functional Stroke Recovery Through Tissue Engineered Niche Neural Constructs, Natasha Topoluk Dec 2013

Functional Stroke Recovery Through Tissue Engineered Niche Neural Constructs, Natasha Topoluk

All Theses

According to the Centers for Disease Control and Prevention, stroke is statistically responsible for 1 in every 19 deaths of American citizens.5 Stroke is the leading cause of permanent disability due to the fact that it compromises both cellular and tissue components of the brain, leading to the formation of a physical void within the tissue. Current research approaches address the cellular component by injecting stem cells into this void; however, extremely low cell engraftment, high injected cell death, and overall no matrix regeneration are observed. Additionally, these stem cells do not remain committed to a neural lineage. We propose …


The Effects Of Different Size Gold Nanoparticles On Mechanical Properties Of Vascular Smooth Muscle Cells Under Mechanical Stretching, Tri Kieu Dec 2013

The Effects Of Different Size Gold Nanoparticles On Mechanical Properties Of Vascular Smooth Muscle Cells Under Mechanical Stretching, Tri Kieu

All Theses

The field of nanotechnology research has seen a large growth in the past few decades due to the great potential of novel nano-size material for useful applications such as drug delivery and medical imaging. Also, they are a promising platform for the detection of terrible diseases such as cancer and atherosclerosis. Although these materials hold great promise, there is very limited understanding about the biological effects of these nanoparticles on normal healthy cells, such as vascular smooth muscle cells (VSMCs). The VSMCs are unique cells due to the two distinct phenotype characteristics it can express: a contractile and a synthetic …


Methane Prediction By Nutrient Profiles In Ruminal Continuous Cultures Fed An All Forage Diet Of Bermudagrass Or Annual Ryegrass, Kaylin Young Dec 2013

Methane Prediction By Nutrient Profiles In Ruminal Continuous Cultures Fed An All Forage Diet Of Bermudagrass Or Annual Ryegrass, Kaylin Young

All Theses

Extensive research has been done on the effect of diet on rumen methane (CH4) production, and on developing equations to accurately predict CH4 in cattle. However, the majority of this research has been gathered from feedlot cattle or cattle fed a total mixed ration (TMR). To date, no studies have examined nutrient correlations with CH4 when feeding an all pasture diet of warm season or cool season grasses. This study included two in vitro experiments, one with a warm season forage and one with a cool season forage to see which nutrient characteristics of each forage best correlated with CH4 …


Teaching Methods For A Holistic Computer Graphics Curriculum Incorporating Active Learning Techniques, Zachariah Inks Dec 2013

Teaching Methods For A Holistic Computer Graphics Curriculum Incorporating Active Learning Techniques, Zachariah Inks

All Theses

This paper presents various concepts and techniques for creating an educational pipeline targeted at the field of computer graphics. This proposed pipeline focuses on the teaching of core concepts, core methodologies and finally core techniques employed within the field of computer graphics. Each component is then paired with an example of an active learning strategy used to enlighten and reinforce the abstract ideas behind these components. Throughout this document outlines the importance of supporting a holistic and platform agnostic approach, which sets the foundation for learning of all core computer graphics concepts, methodologies and techniques. The end result is a …


Studies Of Molecular Mechanisms Of Cranberry Mediated Healthspan Promotion In Caenorhabditis Elegans, Sujay Guha Dec 2013

Studies Of Molecular Mechanisms Of Cranberry Mediated Healthspan Promotion In Caenorhabditis Elegans, Sujay Guha

All Dissertations

Extensive studies have demonstrated the potent ability of many nutraceuticals to alleviate the symptoms of aging and stress. We found that cranberry extract (CBE) supplementation at an optimum concentration could prolong Caenorhabditis elegans (C. elegans) lifespan in a manner of daf-16 and osr-1 dependence. Considering that aging is a progressive degeneration of physiological functions, it is intriguing to know whether CBE consumption may delay the age-related degenerative changes in animals. Thus, we examined the effect of CBE consumption on healthspan in C. elegans populations with different ages and age-related disorders. Our results suggest that long-term CBE supplementation leads to a …


Vascular Nanomedicine: Site Specific Delivery Of Elastin Stabilizing Therapeutics To Damaged Arteries, Aditi Sinha Dec 2013

Vascular Nanomedicine: Site Specific Delivery Of Elastin Stabilizing Therapeutics To Damaged Arteries, Aditi Sinha

All Dissertations

Elastin, a structural protein in the extra-cellular matrix, plays a critical role in the normal functioning of blood vessels. Apart from performing its primary function of providing resilience to arteries, it also plays major role in regulating cell-cell and cell-matrix interactions, response to injury, and morphogenesis. Medial arterial calcification (MAC) and abdominal aortic aneurysm (AAA) are two diseases where the structural and functional integrity of elastin is severely compromised. Although the clinical presentation of MAC and AAA differ, they have one common underlying causative mechanism--pathological degradation of elastin. Hence prevention of elastin degradation in the early stages of MAC and …