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Full-Text Articles in Life Sciences

Nuclear Envelope Rupture And Genomic Instability In Cancer, Yuntao Xia Jan 2019

Nuclear Envelope Rupture And Genomic Instability In Cancer, Yuntao Xia

Publicly Accessible Penn Dissertations

Cell migration through narrow interstitial space in tissues is commonly seen in both physiological and pathological conditions. The bulky stiff nucleus in the cell becomes a barrier during constricted migration making such process pore-size dependent with smaller pores exponentially alleviate the passage capability. However, in some cases, cells actively deform their nuclei to squeeze through constrictions, during which nuclear envelope can rupture. As key intracellular processes such as DNA replication and transcription take place in the nucleus, the consequences of nuclear envelope rupture become intriguing.

In the past five years, we have observed increased DNA damage, cell cycle delay and ...


Development And Utilization Of Ultrasound Imaging Techniques To Evaluate The Role Of Vascularity In Adult And Aged Rat Achilles Tendon Healing, Corinne Nicole Riggin Jan 2018

Development And Utilization Of Ultrasound Imaging Techniques To Evaluate The Role Of Vascularity In Adult And Aged Rat Achilles Tendon Healing, Corinne Nicole Riggin

Publicly Accessible Penn Dissertations

Tendons are hypovascular tissues, undergoing angiogenesis only during development, wound healing, and pathogenesis. Injured tendons exhibit a healing response with vascular ingrowth during the proliferative phase and vascular regression during remodeling. Despite this normal healing response, tendons never fully regain their original structure or composition. Additionally, aging further increases tendon risk of rupture and impairs healing response. Since the optimal vascularization level and timing during tendon healing is currently unknown, modulating the vascular response during healing could elucidate the role of angiogenesis in tendon injury and ultimately improve the tendon healing outcome. Furthermore, new ultrasound technologies allow for the evaluation ...


Force Transmission Mechanisms In Fibrous Biological Structures, Hossein Ahmadzadeh Jan 2017

Force Transmission Mechanisms In Fibrous Biological Structures, Hossein Ahmadzadeh

Publicly Accessible Penn Dissertations

Understanding the mechanism of the load bearing and force transmission throughout fibrous biological structures can help decode complex physiological and pathological phenomena and provide insight into possible therapeutic solutions. Fibrous structures are characterized by one-dimensional fibers stabilized by cross-linking proteins and molecules. Preferentially aligned fibers form well-organized parallel bundles, whereas randomly distributed fibers create isotropic three-dimensional networks. Tendons, composed of staggered arrangements of collagen fibrils, and axonal cytoskeleton in neurons, composed of alternate rows of microtubules, are two instances of structures with aligned fibers. Collagen fibrous networks which make up the extracellular matrix (ECM) of connective tissues are an example ...


Mechanics Of Fluctuating Elastic Plates And Fiber Networks, Xiaojun Liang Jan 2017

Mechanics Of Fluctuating Elastic Plates And Fiber Networks, Xiaojun Liang

Publicly Accessible Penn Dissertations

Lipid membranes and fiber networks in biological systems perform important mechanical functions at the cellular and tissue levels. In this thesis I delve into two detailed problems -- thermal fluctuation of membranes and non-linear compression response of fiber networks. Typically, membrane fluctuations are analysed by decomposing into normal modes or by molecular simulations. In the first part of my thesis, I propose a new semi-analytic method to calculate the partition function of a membrane. The membrane is viewed as a fluctuating von Karman plate and discretized into triangular elements. Its energy is expressed as a function of nodal displacements, and then ...


Multiscale Mechanical, Structural, And Compositional Response Of Tendon To Static And Dynamic Loading During Healing, Benjamin Freedman Jan 2017

Multiscale Mechanical, Structural, And Compositional Response Of Tendon To Static And Dynamic Loading During Healing, Benjamin Freedman

Publicly Accessible Penn Dissertations

The extracellular matrix (ECM) is a major component of the biomechanical environment with which tendon cells (tenocytes) interact. Alterations to matrix structural and mechanical properties due to mechanical loading may promote normal tendon homeostasis or create pathological conditions. For example, fatigue loading of tendon elevates collagen fiber waviness (crimp), which correlates linearly with tissue laxity. The tendon ECM may also be altered following tendon injury. Aberrant tissue phenotypes caused by tendon ruptures are exemplified not only at transcript and protein levels, but also can extend to include disorganized collagen structure, inferior mechanical properties, and reduced in vivo limb function in ...


Colonial Korea And The Olympic Games, 1910–1945, Seok Lee Jan 2016

Colonial Korea And The Olympic Games, 1910–1945, Seok Lee

Publicly Accessible Penn Dissertations

This dissertation examines how Koreans received and consumed the Olympic Games under Japanese colonial rule (1910–1945). Although a growing body of research on colonial Korea addresses a range of topics beyond politics and economy, sports is still a relatively neglected topic in this field. By exploring Olympic fever in colonial Korea, this study shows how multifaceted aspects of Korean society became a part of the global sports world. Korean athletes participated in the 1932 Summer, 1936 Winter, and 1936 Summer Games as part of the Japanese delegation, attracting much attention from members of all walks of life in colonial ...


The Courage Trial: A Phase Ii Randomized Clinical Trial To Evaluate The Dose-Response Effects Of Exercise On Prognostic Biomarkers Among Colon Cancer Survivors, Justin Charles Brown Jan 2016

The Courage Trial: A Phase Ii Randomized Clinical Trial To Evaluate The Dose-Response Effects Of Exercise On Prognostic Biomarkers Among Colon Cancer Survivors, Justin Charles Brown

Publicly Accessible Penn Dissertations

Observational epidemiologic data suggest that participation in physical activity after a diagnosis of colon cancer reduces the risk of cancer recurrence, cancer-specific mortality, and all-cause mortality. However, the biologic mechanisms that mediate the relationship between physical activity and disease outcomes among colon cancer survivors have not been characterized. Excess visceral adipose tissue and hyperinsulinemia promote the growth and progression of existing micro-metastases and the development of new distant metastases. Exercise reduces visceral adipose tissue and hyperinsulinemia among non-diabetic persons with obesity. However, it is unknown if exercise alters visceral adipose tissue and hyperinsulinemia among colon cancer survivors. We conducted a ...


Tensile Mechanics Of The Knee Meniscus In The Context Of Cracks: Failure And Fracture Mechanisms, Strain Concentrations, And The Effect Of Specimen Shape, John Mark Peloquin Jan 2016

Tensile Mechanics Of The Knee Meniscus In The Context Of Cracks: Failure And Fracture Mechanisms, Strain Concentrations, And The Effect Of Specimen Shape, John Mark Peloquin

Publicly Accessible Penn Dissertations

Knee meniscus tears (cracks) are a major cause of knee dysfunction and osteoarthritis, but little is known about how they grow or what effects they have on meniscus mechanics. The objective of this work was to investigate the mechanics and failure of crack-free and cracked meniscus in uniaxial tension, with specific attention to failure mechanisms (fracture and bulk rupture) and local strain concentrations. A finite element model was used to find a test configuration likely to cause fracture and crack propagation. Center cracks with a 45° crack–fiber angle were selected for producing large fiber stresses, and 90° edge cracks ...


Mechanical Crosstalk Between Cell-Cell And Cell-Matrix Adhesions And Modulation Of N-Cadherin-Mediated Proliferation By Cell Spreading, Keeley Ling Mui Jan 2015

Mechanical Crosstalk Between Cell-Cell And Cell-Matrix Adhesions And Modulation Of N-Cadherin-Mediated Proliferation By Cell Spreading, Keeley Ling Mui

Publicly Accessible Penn Dissertations

Cell-matrix and cell-cell adhesions are often characterized as functionally distinct adhesion systems within the cell that mediate different proliferative outcomes. In contrast to the widely accepted pro-proliferative effect of cell-matrix adhesion, the proliferative effect of cadherin-dependent cell-cell adhesion remains unresolved. While the majority of studies demonstrate that cadherins mediate contact inhibition of proliferation, there have also been compelling reports of cadherins stimulating cell cycling. Here, we show that matrix stiffness is the mechanistic basis for crosstalk between N-cadherin at cell-cell junctions and focal adhesion kinase (FAK) at cell-matrix adhesions, and that this interplay between adhesive systems modulates the proliferative role ...


The Connection Of Composition, Structure, And Dynamic Processes To Tendon Mechanics: Structure-Function Relationships In Collagen V Deficient Tendons, Brianne Kathryn Connizzo Jan 2015

The Connection Of Composition, Structure, And Dynamic Processes To Tendon Mechanics: Structure-Function Relationships In Collagen V Deficient Tendons, Brianne Kathryn Connizzo

Publicly Accessible Penn Dissertations

Tendons are able to withstand the broad range of stresses and strains via their finely tuned composition and structure. In addition, tendons undergo a coordinated set of dynamic responses, specifically collagen uncrimping, re-alignment, sliding and deformation, within the matrix. To date, a complete understanding of the hierarchical structure-function relationships in tendon is lacking. Therefore, the overall goal of this thesis was to measure tendon structure and function in a mouse supraspinatus model of altered structure, and to analyze links between mechanical properties, dynamic processes and composition/structure using a series of statistical analyses. In the studies presented here, we used ...


Adaptations Of The Supraspinatus Tendon And Muscle In A Rat Model Of Exercise, Sarah Ilkhanipour Rooney Jan 2015

Adaptations Of The Supraspinatus Tendon And Muscle In A Rat Model Of Exercise, Sarah Ilkhanipour Rooney

Publicly Accessible Penn Dissertations

Rotator cuff tendon and muscle can beneficially adapt to exercise, but it is unknown how acute responses following a single bout of exercise lead to chronic, beneficial adaptations. To develop new prevention and treatment strategies for overuse injuries, we must first characterize how tissues adapt to non-injurious loading. One feature that may distinguish beneficial and detrimental responses are pathways associated with inflammation and tissue healing, including activation of the arachidonic acid cascade and matrix turnover facilitated by matrix metalloproteinases (MMPs). The objective of this dissertation was to characterize temporal, acute and chronic responses of the rat supraspinatus to non-injurious exercise ...


The Effect Of Cell Contractility And Packing On Extracellular Matrix And Soft Tissue Rheology, Anne Sofieke Geertruide Van Oosten Jan 2015

The Effect Of Cell Contractility And Packing On Extracellular Matrix And Soft Tissue Rheology, Anne Sofieke Geertruide Van Oosten

Publicly Accessible Penn Dissertations

In the past decades it has become clear that the mechanical properties of tissues are important for healthy functioning. The mechanical properties of tissues and their load-bearing components found in the extracellular matrix (ECM) have been tested mechanically to provide more insight. However, there is a discrepancy between tissue and ECM mechanics. In this thesis this discrepancy is investigated with a novel multiaxial rheology method, which addresses a physiologically relevant combination of shear and axial strains. Blood clots are used to study the effect of cell traction and cell packing on ECM mechanics.

The results show that ECM networks compression ...


Nuclear Connectivity In Mesenchymal Stem Cell Differentiation And Its Role In Mechanotransduction, Tristan Patrick Driscoll Jan 2015

Nuclear Connectivity In Mesenchymal Stem Cell Differentiation And Its Role In Mechanotransduction, Tristan Patrick Driscoll

Publicly Accessible Penn Dissertations

Mechanical forces transmitted through the cellular microenvironment are critically important for tissue development, homeostasis, and degeneration, particularly for tissues in the musculoskeletal system that play primary load bearing roles. When these tissues degenerate, their limited healing capacity has lead many to propose tissue engineering strategies in order to provide functional replacements. While native tissue structural and mechanical benchmarks are commonly used to quantify and validate outcomes for tissue engineering and to refine experimental approaches, these same benchmarks have not yet been extended to the cellular and sub-cellular level. This is true despite the fact that it is at this length ...


Validation And Application Of An Intervertebral Disc Finite Element Model Utilizing Independently Constructed Tissue-Level Constitutive Formulations That Are Nonlinear, Anisotropic, And Time-Dependent, Nathan Jacobs Jan 2014

Validation And Application Of An Intervertebral Disc Finite Element Model Utilizing Independently Constructed Tissue-Level Constitutive Formulations That Are Nonlinear, Anisotropic, And Time-Dependent, Nathan Jacobs

Publicly Accessible Penn Dissertations

Finite element models are advantageous in the study of intervertebral disc mechanics as the stress-strain distributions can be determined throughout the tissue and the applied loading and material properties can be controlled and modified. However, the complicated nature of the disc presents a challenge in developing an accurate and predictive disc model, which has led to limitations in finite element geometries, material constitutive models and properties, and model validation. The objective of this dissertation is to develop a new finite element model of the intervertebral disc, to validate the model's nonlinear and time-dependent responses without tuning or calibration, and ...


Intervertebral Disc Structure And Mechanical Function Under Physiological Loading Quantified Non-Invasively Utilizing Mri And Image Registration, Jonathon H. Yoder Jan 2014

Intervertebral Disc Structure And Mechanical Function Under Physiological Loading Quantified Non-Invasively Utilizing Mri And Image Registration, Jonathon H. Yoder

Publicly Accessible Penn Dissertations

The intervertebral discs (IVD) functions to permit motion, distribute load, and dissipate energy in the spine. It performs these functions through its heterogeneous structural organization and biochemical composition consisting of several tissue substructures: the central gelatinous nucleus pulposus (NP), the surrounding fiber reinforced layered annulus fibrosus (AF), and the cartilaginous endplates (CEP) that are positioned between the NP and vertebral endplates. Each tissue contributes individually to overall disc mechanics and by interacting with adjacent tissues. Disruption of the disc's tissues through aging, degeneration, or tear will not only alter the affected tissue mechanical properties, but also the mechanical behavior ...


The Role Of Scapular Dyskinesis In Rotator Cuff And Biceps Tendon Pathology, Katherine E. Reuther Jan 2014

The Role Of Scapular Dyskinesis In Rotator Cuff And Biceps Tendon Pathology, Katherine E. Reuther

Publicly Accessible Penn Dissertations

Shoulder tendon injuries including impingement, rotator cuff disease, and biceps tendon pathology are common clinical conditions and are a significant source of joint pain, instability, and dysfunction. These injuries may progress into partial tears then to complete tendon ruptures, which have limited healing capacity even when surgically repaired. These injuries are frequently seen in the presence of abnormal scapulothoracic joint kinematics (termed scapular dyskinesis). However, the cause and effect relationship between scapular dyskinesis and shoulder injury has not been directly defined. Additionally, while the incidence of shoulder injuries and recurrent failure of repairs is well-documented, the mechanisms behind them are ...


Defining The Role Of Mechanical Signals During Nerve Root Compression In The Development Of Sustained Pain And Neurophysiological Correlates That Develop In The Injured Tissue And Spinal Cord, Kristen Nicholson Jan 2013

Defining The Role Of Mechanical Signals During Nerve Root Compression In The Development Of Sustained Pain And Neurophysiological Correlates That Develop In The Injured Tissue And Spinal Cord, Kristen Nicholson

Publicly Accessible Penn Dissertations

Cervical nerve root injury commonly leads to pain. The duration of an applied compression has been shown to contribute to both the onset of persistent pain and also the degree of spinal cellular and molecular responses related to nociception that are produced. This thesis uses a rat model of a transient cervical nerve root compression to study how the duration of an applied compression modulates both peripherally-evoked activity in spinal cord neurons during a root compression and the resulting neuronal and glutamatergic responses in the nerve root and spinal cord. Studies define the compression duration threshold that inhibits peripherally-evoked action ...


Microscale Measurements Of Cell And Tissue Mechanics In Three Dimensions, Wesley Legant Jan 2012

Microscale Measurements Of Cell And Tissue Mechanics In Three Dimensions, Wesley Legant

Publicly Accessible Penn Dissertations

Two-dimensional (2D) studies have revealed that mechanical forces drive cell migration and can feedback to regulate proliferation, differentiation and the synthesis/remodeling of extracellular matrix (ECM) proteins. Whether these observations can be translated to clinical settings or be utilized for tissue engineering will depend critically on our ability to translate these findings into physiologically relevant three-dimensional (3D) environments. The general goal of this dissertation has been to develop and apply new technologies capable of extending studies of cell and tissue mechanics into 3D environments.

In the first project, we measured both shear and normal traction forces exerted by cells cultured ...


Relationships Between Decorin And Biglycan, Structure And Tendon Mechanics Using Mutant Mouse Models, Leann Dourte Jan 2011

Relationships Between Decorin And Biglycan, Structure And Tendon Mechanics Using Mutant Mouse Models, Leann Dourte

Publicly Accessible Penn Dissertations

Tendons have a complex mechanical behavior that depends on their composition and structure. Understanding structure-function relationships may elucidate important differences in the functional behaviors of specific tendons and guide targeted treatment modalities and tissue engineered constructs. Specifically, the interactions of small leucine-rich proteoglycans (SLRPs) with collagen fibrils, association with water and role in fibrillogenesis suggest that SLRPs may play an important role in tendon mechanics. Some studies have assessed the role of SLRPs in the mechanical response of tendon, but the relationships between sophisticated mechanics, assembly of collagen and SLRPs have not been well characterized. Therefore, the aim of this ...