bluuebunny/crossref_metadata_2025 huggingface dataset:
Eye-Specific Measurement of the Microstructure and Biomechanics of the Human Lamina Cribrosa
Authors: Sigal Ian A. , Grimm Jonathan L. , Jan Ning-Jiun , Reid Korey , Brown Donald J.
Published: July 2013

Loss of vision in glaucoma, one of the leading causes of blindness worldwide, is due to damage to the axons of cells that transmit visual information from the retina to the brain [1]. This damage is believed to initiate in the lamina cribrosa (LC), a specialized structure in the back of the eye. Elevated intraocular pressure (IOP) is the main risk factor for the development of glaucoma, yet the mechanisms by which an elevated IOP leads to loss of vision are not understood. This is, in part, because measuring directly the effects of IOP on the LC is very challenging. Thus most of what is known about the structure of the LC and of the effects of IOP on it has been determined from indirect measures or from analysis of histological samples. Histological analysis, however, is problematic because it susceptible to artifacts, such as shrinkage and warping.
Effects of Dynamic Loading on Cell Viability in Intervertebral Disc
Authors: Zhu Qiaoqiao , Gu Weiyong
Published: July 2013

Sufficient nutrient supply has long been regarded as a crucial factor for maintaining intervertebral disc (IVD) cell viability and preventing IVD degeneration1,2. Due to avascular nature of the tissue, nutrients for IVD cells are transported, mainly by diffusion, through the dense extracellular matrix of the tissue from the peripheral and endplate vasculatures. Experimental studies on the effects of nutrient deprivation on IVD cell viability showed that glucose is the most critical nutrient affecting the cell density in IVD3–5. Because of the difficulties in studying mechano-biology of human IVD in vivo, numerical simulations are necessary to investigate how the disturbances of biological, physical, and chemical signals can affect the cellular metabolism and viability in IVD. However, to date, there is no adequate theoretical model that is able to describe the change of cell density in IVD under dynamic conditions. Therefore, the objective of this study was to develop a new constitutive model for cell growth/death in human IVD and to analyze the cell metabolism and cell viability in IVD under dynamic, mechanical loading conditions using numerical methods based on the mechano-electrochemical mixture theory6,7.
Device Specific Aortic Outflow Cannula Jets Studied Using 2D PIV and High-Performance 3D CFD Simulation
Authors: Menon Prahlad G. , Teslovich Nikola , Chen Chia-Yuan , Sotiropoulos Fotis , Undar Akif , Pekkan Kerem
Published: July 2013

In the US, approximately 1 in 100 children are born with a clinically significant congenital heart defect (CHD). The palliative repair of these defects requires complex biventricular and univentricular surgical operations in newborns often smaller than 2 kg. However, recovery after neonatal intervention remains suboptimal 1. A major component of these surgeries is the cardiopulmonary by-pass (CPB) procedure which if prolonged can potentially lead to neurological complications and developmental defects in a young patient. During CPB, tiny aortic cannulae (2–3 mm inner diameter), with micro-scale blood-wetting features transport relatively large blood volumes (0.3 to 1.0 L/min) resulting in high blood flow velocities. Our recent 3D computational fluid dynamics (CFD) simulations of jet flows in device specific cannulae 2 have indicated that the turbulent jet wake at high physiological neonatal extracorporeal life support (ECLS) circuit blood flow rates can potentially have damaging hemolytic effects, when evaluated in a cuboidal flow domain, as well as in in-silico aortic insertion configurations. Such severe flow conditions can result in platelet activation, vascular injuries and blood damage. Despite these risks, cannulation methods have received little attention compared to the effort expended to assure the safety and efficacy of the mechanical circulatory support blood pumps. Qui et al 3 report that cannula problems are the second most frequently reported mechanical complication in ECLS therapy for respiratory cases and the third most frequent complication in cardiac cases. The purpose of this study is to quantitatively evaluate the jet wake region of two popular 8FR pediatric cannulae, DLP Medtronic 77008 and RMI FEM II – 008 – AT (inner diameter ∼1850 microns), using stereo particle image velocimetry (PIV) to validate numerically computed flow fields.
CFD Challenge: Computational Hemodynamics Analysis of Patient-Specific Internal Carotid Artery Aneursym Using an In-House Finite Difference Cardiovascular Flow Solver
Authors: Menon Prahlad G. , Sotiropoulos Fotis , Pekkan Kerem
Published: July 2013

An important focus of our cardiovascular fluid mechanics studies is the development and application of computational fluid dynamics (CFD) tools for patient-specific evaluation of internal hemodynamics in vascular anatomies. The validated unsteady internal flow solver utilized in this study has been applied to a multitude of cardiovascular geometries, particularly Fontan surgical anastomoses, pediatric venous flow confluences 1, idealized developing embryonic chick-heart models 2, neonatal aortic arch models and several complex geometries involving jet flow behavior 3. We have also recently started to explore the capability of this solver for evaluating internal flows and wall shear stresses in abdominal aortic aneursyms. For the 2012 SBC Challenge, 3D transient CFD simulations have been performed for a patient-specific internal carotid artery aneurysm case.
The Effect of Prosthetic Foot Component Stiffness on Gait Initiation and Termination of Transtibial Amputees
Authors: Peterson Travis J. , Roland Michelle , Adamczyk Peter , Hahn Michael E.
Published: July 2013

Matching a prosthetic foot to meet the activity requirements of the user can be a difficult process. The ideal stiffness characteristics of different functional activities may vary. This variation dictates that the prescribed foot must be a compromise of multiple ideals due to functional necessity. The effects of lower limb stiffness have been studied in regards to their ability to reproduce “normal” lower limb mechanics [1,2]. Other studies have tracked gait stability and performance measures for lower limb amputees during gait initiation and termination [3–5]. However, it remains unknown what effects prosthetic stiffness may have on amputee function during gait initiation and termination. The objective of this study was to compare the effects of different component stiffness ranges on locomotion and stability measures during gait initiation and termination
Tensile Properties and Collagen Organization of the Rat Cervix
Authors: Wagoner Johnson A. J. , Poellmann M. , McFarlin B. L. , Chien E. K.
Published: July 2013

Preterm birth is the leading cause of newborn death. Many premature survivors have serious and lifelong complications like cerebral palsy, learning and developmental disabilities, and hearing and vision impairment [1]. An accurate, predictive tool for preterm birth risk assessment does not exist. This research works towards developing tools based on mechanical measures of the cervix to assess risk for preterm birth.
MRI-Based Inflow Boundary Conditions for Patient Specific Fluid Structure Interaction Modeling of Abdominal Aortic Aneurysms
Authors: Chandra Santanu , Raut Samarth , Jana Anirban , Biederman Robert W. , Doyle Mark , Muluk Satish C. , Finol Ender A.
Published: July 2013

Rupture of abdominal aortic aneurysm (AAA) is the 10th leading cause of death for men over age of 50 in US. The decision for surgical intervention is currently based on aneurysm diameter or its expansion rate. However, the use of these criteria for all patients is debatable. For example, small aneurysms do rupture or become symptomatic before reaching the critical diameter. Computationally predicted mechanical wall stress is considered a viable alternative criterion for rupture risk assessment. Hence, it is important to evaluate the effect of different modeling approaches on the accuracy of the predicated AAA wall stress. For computational solid stress (CSS) analysis or finite element analysis (FEA), a uniform static or transient intraluminal pressure is generally applied on the wall-lumen surface whereas in fluid-structure interaction (FSI) modeling the wall-lumen surface experiences transient and non-uniform fluid stress. An earlier comparison on idealized AAA models [1] revealed that static and transient CSS underestimate the peak wall stress (PWS) by an average 20–30% for variable wall thickness and 10% for uniform wall thickness when compared to fully coupled FSI. However, FSI-predicted stresses and strains were observed to be sensitive to inflow and outflow boundary conditions, warranting further study on a more accurate approach for FSI modeling. Though significant work has been performed on modeling outflow boundary conditions [2], studies on the sensitivity of computed stress or strain to the type of FSI inflow boundary condition is scarce [2–4]. We hypothesize that a FSI framework with a patient specific velocity boundary condition derived from magnetic resonance imaging (MRI) data applied to patient specific AAA geometry would provide better accuracy of PWS calculations compared to a FEA model. In this work, we present a framework where the AAA geometry is reconstructed from computed tomography (CT) images, on which FSI simulations were performed with inlet velocity components extracted from patient MR images of the abdominal aorta. Fully coupled FSI simulations were performed and results were compared with CSS simulations with uniform transient pressure boundary conditions.
Multi-Scale Structural and Tensile Mechanical Response of Annulus Fibrosus to Osmotic Loading
Authors: Han Woojin M. , Nerurkar Nandan L. , Smith Lachlan J. , Jacobs Nathan T. , Mauck Robert L. , Elliott Dawn M.
Published: July 2013

The annulus fibrosus (AF) is a multi-lamellar fibrocartilagenous ring in the intervertebral disc. The variation of biochemical composition from the outer to the inner AF is largely responsible for the heterogeneous mechanical properties. In vitro tissue-level studies require mechanical testing in aqueous buffers to avoid tissue dehydration. The varying glycosaminoglycan (GAG) contents from outer to inner AF suggest that the response to high and low PBS osmolarity may also be different with radial position. Previous studies in tendon and ligament have been conflicting: soaking tendon fascicles in PBS decreased tensile modulus1 and treating ligament in buffer had no effect on modulus.2
Virtual Deployment of Self-Expanding Stents in Aneurysmatic Intracranial Vessels: Do Stent Design and Vessel Geometry Matter?
Authors: Iannaccone F. , De Bock S. , De Santis G. , De Beule M. , Mortier P. , Vermassen F. , Segers P. , Verhegghe B.
Published: July 2013

Cerebral aneurysms are weakened, balloon like dilations of the intracranial vessels. Rupture of these swelled vessels, with a prevalence of 1 to 5% not uncommon [1], is associated with a high mortality and morbidity [2]. Clipping (by craniotomy) or coiling (passing platinum wires into the aneurysm) is often performed to reduce the risk of rupture. Coiling of wide necked or fusiform aneurysms, which is not easily achieved without risk of coil displacement, is often assisted by placement of intracranial stents, serving as a scaffold for the platinum coils. Cerebral stents can be of either closed or open cell design. Both designs have shown to be successful at assisting coiling, yet each design has its own strengths and weaknesses [3].
Dynamic Simulation of Upper Limb Movement in Two Software Platforms
Authors: Saul Katherine R. , Goehler Craig M. , Daly Melissa , Vidt Meghan E. , Velisar Anca , Murray Wendy M.
Published: July 2013

There are several opensource or commercially available software platforms widely used for the development of dynamic simulations of movement. While computational approaches to calculating the dynamics of a musculoskeletal model are conceptually similar across platforms, differences in implementation may influence simulation output. To understand predictions made using simulation, it is important to understand differences that may result from the choice of model or platform. Our aims were to 1) develop a musculoskeletal model of the upper limb suitable for dynamic simulation and 2) evaluate the influence of the choice between SIMM-SD/Fast and OpenSim simulation platforms on gravity- and EMG-driven simulations of movement.
A Wave Reflection Analog Extension for Reduced Order Vocal Fold Investigations With Asymmetric Intraglottal Flows
Authors: Erath Byron D. , Peterson Sean D. , Zañartu Matias , Plesniak Michael W.
Published: July 2013

Voiced speech involves complex fluid-structure-acoustic interactions. When a critical lung pressure is achieved, the vocal folds are pushed apart inciting self-sustained oscillations. The interplay between the aerodynamic forces and the myoelastic tissue properties produces robust oscillation of the vocal folds. The pulsatile nature of the flow as it emanates from vocal folds creates an oscillatory pressure field which acoustically excites the vocal tract and ultimately forms intelligible sound. Recently, it has been shown that the acoustic pressures are high enough in magnitude that they modulate the static fluid pressures which drive the flow.1 This coupling effect creates a feedback loop with the fluids, acoustics, and vocal fold dynamics becoming interconnected. Consequently, speech science investigations that aim to capture the relevant physics must consider all three components to yield credible, clinically-relevant results.
Aerosol Deposition Study of Subject-Specific Upper Respiratory Model
Authors: Fratino Anthony L. , Hyun Sinjae , Kim Chong S.
Published: July 2013

An accurate model of the human respiratory system allows health professionals to gain insight into the interactions between particulate matter (PM) and the exposed surfaces of the lung airways. Respiratory dose simulations and modeling are frequently used for evaluating health effects of inhaled toxic substances [1–4] and for analyzing the risk potentials of inhaled toxic or harmful PM such as vehicle emissions [4,5].
Umbilical Cord Artery Mechanical Properties in Pre-Term Neonates at Various Ages
Authors: Nye Kevin S. , Esplin M. Sean , Monson Kenneth L.
Published: July 2013

Premature and very low birthweight (VLBW) infants are susceptible to numerous injuries during, and after parturition. If these injuries are neurological in nature, they can result in long-term cognitive and motor skill deficiencies. Cerebral hemorrhaging is a disease that has disastrous consequences on preterm and VLBW infants, and the mechanism for this type of hemorrhaging is currently not known. Bleeding in the ventricle region of the brain is termed intraventricular hemorrhage (IVH) and occurs in 32% of infants with birth weights less than 1500 grams and born prior to 32 weeks gestation[1]; 75% of these will experience long-term neurological disabilities[2]. A lack of tissue structure of the cerebral vasculature in early stages of development is a possible underlying cause for such high occurrences of IVH[3,4,5]. Mechanical characterization of neonatal vasculature could show structural underdevelopment as the underlying cause of IVH and provide valuable insight into neonatal vascular development. We previously characterized the mechanical properties of whole umbilical cord arteries and found a correlation between vessel stiffness and gestational age[6]. Considerations of the helical structure of late term umbilical cord vessels prompted a revisit of the characterization of the vessels with altered testing methods. To negate the effects of the vessels’ tortuous structure on stiffness values, we tested axial and circumferential small strips of human umbilical cord artery at various gestational time.
Step Count Validation of a Tri-Axial Accelerometer During Walking and Jogging
Authors: Fortune Emma , Lugade Vipul , Morrow Melissa , Kaufman Kenton
Published: July 2013

Gait analysis is an important tool in assessing the health and activity levels of patients and regular physical activity has been associated with health improvements in a number of populations. Step counting is one of the most commonly used measures of physical activity [1] and many studies have investigated the use of wearable sensors for step counts [2–4]. Their small size and light weight mean that they may be used in a free living environment and are suitable for home deployment. One of the main issues associated with step counts as a measure of physical activity is that a very high level of accuracy in step detection is needed.
Validation of Static and Dynamic Activity Detection Using a Tri-Axial Accelerometer and Video
Authors: Lugade Vipul , Fortune Emma , Morrow Melissa , Kaufman Kenton
Published: July 2013

Recording body accelerations has been investigated previously to monitor health, metabolic energy expenditure, postural sway and falls [1]. Activity monitoring and the subsequent analysis of the accelerometry data have also proven useful in detecting physical activity levels among Parkinson’s [2] and osteoarthritis patients [3].
Biomechanical Effects of Radiofrequency Ablation With Simultaneous Cryogenic Anchoring
Authors: Boronyak Steven M. , Merryman W. David
Published: July 2013

Mitral valve (MV) disease is the most common form of heart valve disease, occurring in approximately 2% of the population and resulting in 43,000 open-chest surgical procedures every year [1]. One subtype is mitral valve prolapse (MVP), which is often characterized by severe regurgitant flow, thickened and enlarged leaflets, and disrupted and mechanically compromised collagen architecture.
In Vivo Administration of an Inflammatory Stimulant can Trigger Loss of Biomechanical and Biochemical Properties of the Intervertebral Disc
Authors: Rajan Neena , Stetson Nate , Maidhof Robert , Levine Mitchell , Chahine Nadeen
Published: July 2013

Human intervertebral disc (IVD) degeneration is accompanied by chronic inflammation, particularly seen in the elevated levels of pro-inflammatory cytokines IL-1β and TNF-α [1–3]. Animal models of disc degeneration (DD) using stab or laceration of the disc generally reproduce morphological changes of IVD degeneration. However, inflammatory changes in these models are thought to be acute and transient post injury [4–6]. The goal of this study is to explore the effect of direct inflammatory stimulation of the IVD on disc biochemical and biomechanical properties in vivo. We utilize lipopolysaccharide (LPS), an inflammatory stimulant that provokes secretion of multiple cytokines by disc cells. We have previously shown that direct injection of LPS into the disc results in significantly higher protein levels of IL-1β, TNF-α, HMGB-1 and MIF vs. sham injection up to 7 days post administration [7]. The goal of this study is to explore the dose-dependent response of this inflammatory stimulation on the biochemical and biomechanical properties of IVD in vivo. We hypothesize that LPS stimulation mimics the pathophysiology of DD by triggering a group of cytokines that are associated with IVD degeneration. LPS is administered using micro needles (<10% disc height) in order to minimize the potential disruption by needle injection.
5-HT2B Antagonism Inhibits Strain- and Cytokine-Dependent Formation of Calcific Nodules by Aortic Valve Interstitial Cells
Authors: Hutcheson Joshua D. , Chen Joseph , Ryzhova Larisa M. , Merryman W. David
Published: July 2013

The progression of aortic valve (AV) disease is often characterized by the formation of calcific nodules on thickened AV leaflets, limiting the biomechanical function of the valve. In these cases, the association of extracellular Ca2+ with phosphates remaining in cellular debris within the decellularized scaffolds has been proposed to lead to the nucleation and growth of calcific nodules. In native tissue, calcification is thought to be a more active process involving AV interstitial cells (AVICs). AVICs have been shown to form nodule-like structures in vitro through differentiation to a phenotype with osteogenic character. Additionally, in vitro nodules are characterized by activated smooth muscle α-actin (αSMA) positive AVICs and high levels of apoptosis [1–2]. Mechanical strain has also been shown to influence nodule formation in excised AV leaflets [3]. Our lab has recently developed a model system that recapitulates the formation of calcific nodules in vitro [4]. AVICs treated with TGF-β1 for 24 h prior to the addition of 15% cyclic strain in a Flexcell strain system form nodules that appear to be dependent upon the initiation of AVIC activation. These observations are consistent with previous studies that have shown that αSMA expression is required for nodule formation by AVICs in static culture, with statins shown to inhibit in vitro nodule formation [1]. However, retrospective epidemiological studies have shown that these drugs may not be as effective in preventing calcific valve disease in patients [5]. Additionally, the molecular target and relevant pathways for statins in AVICs remain largely unknown. Therefore, a therapeutically relevant target to prevent AVIC activation and subsequent nodule formation is greatly needed. In this study we investigated the ability of antagonists to 5-HT2B, a receptor known to be upstream of TGF-β1, to oppose strain- and TGF-β1-induced AVIC activation and nodule formation. We also assessed the efficacy of an antagonist to a receptor, the angiotensin II type I receptor (AT1R), known to crosstalk with both 5-HT2B and TGF-β1 signaling in other cell types in inhibiting AVIC nodule formation. Our results indicate that 5-HT2B antagonism inhibits AVIC activation and nodule formation by blocking non-canonical TGF-β1 signaling, whereas AT1R antagonism does not inhibit these outcomes. We believe that the results of this study may indicate novel therapeutic targets to prevent the progression of AV calcification.
Aortic Valve Interstitial Cell Activation Does Not Occur at Low Tissue Stiffness During Embryogenesis
Authors: Chun Young Wook , Barnett Joey , Merryman W. David
Published: July 2013

An estimated 2.5 percent of the American population has heart valve (HV) disease and more than 100,000 US patients require a prosthetic valve replacement each year [1]. However, prosthetic valves can cause accelerated calcification leading to recurrence of HV disease in patients [2]. Thus, the development of a suitable tissue-engineered heart valve (TEHV) would greatly benefit patients with HV disease. Aortic valve interstitial cells (AVICs) play a crucial role in the progression of aortic valve disease as well as the maintenance of normal valve. Therefore, in order to design a suitable TEHV, these specialized cells need to be better understood. AVICs are known to synthesize ECM and express matrix degrading enzymes and their inhibitors that mediate and regulate remodeling of ECM components [3]. Interestingly, it was recently established that AVICs sense the stiffness of their surrounding ECM in vivo and are phenotypically responsive to mechanical cues with AVICs differentiating into myofibroblasts or osteoblasts, which are pathologic markers. Specifically, soft collagen gels (∼34kPa) caused less differentiation of AVICs than stiffer collagen gel (∼100kPa) [4]. However, for these experiments the AVICs were cultured on tissue culture polystyrene (TCPS) for at least one passage, and it is likely that AVICs cultured on TCPS might retain modified characteristics of AVICs in tissue prior to seed them on soft gels because of the memory to rigid substrate stiffness. Therefore, in this study, we examined the phenotype and function of AVICs on substrates that mimic ECM stiffness of adult leaflet as well as of developing embryo. In addition, we examine the effects of transforming growth factor-β1 (TGF-β1) which has been the most extensively studied cytokine initiator of fibrotic response of AVICs.
Implementation of Smoothed Profile Modeling in Two Phase Flow Analysis of RBCs in Blood
Authors: Mohaghegh F. , Udaykumar H. S. , Mousel J. , Chivukula V. , Chandran K. B.
Published: July 2013

Analysis of blood as a two phase flow of densely packed finite size particles is a challenging problem that requires a numerical approach that can efficiently and accurately handle large numbers of objects moving through a fluid. Numerical schemes such as the Arbitrary Lagrangian-Eulerian method (ALE), Distributed Lagrangian Multiplier (DLM) or the Immersed Boundary Method (IBM) are useful for simulating particulate flows. However, in the development of a multiscale framework where the dynamics of particles may be evolved at different scales, these methods may be too expensive for the desired resolution.
Dynamic Annular Motion Effects on Mitral Valve Simulation
Authors: Rim Yonghoon , Kee Patrick , Laing Susan T. , McPherson David D. , Chandran Krishnan B. , Kim Hyunggun
Published: July 2013

Characteristics of normal and pathologic mitral valves (MVs) are influenced by physiologic function and component interaction of the mitral apparatus which consists of the annulus, leaflets, chordae tendineae, and papillary muscles (PMs) [1]. In particular, the shape, size, and motion of the mitral annulus are closely related to MV function [2]. Finite element (FE) analysis studies have demonstrated that alterations in the mitral annulus can affect MV motion. However, most of these computational studies have performed the simulations using geometrically simplified MV models created with representative geometric parameters using data collected from normal MVs [3,4]. These computational studies with simplified MV geometric models may not provide patient-specific biomechanical and functional information for clinical evaluation.
Plaque Deformation in Atherosclerotic Porcine Arteries
Authors: Speelman L. , Goffi M. , Akyildiz A. C. , Nieuwstadt H. , Van der Heiden K. , van der Steen A. , Wentzel J. , Gijsen F.
Published: July 2013

Atherosclerosis is the main cause of cardiovascular disease and is characterized by plaque formation, with lipid accumulation in the arterial wall, covered by a fibrous cap. Rupture of such a cap is the main underlying cause of sudden coronary deaths and strokes. Cap rupture occurs when the mechanical stress in the cap exceeds local cap strength. Accurate determination of cap stresses might therefore play an important role in the prediction of cap rupture. An important determinant of plaque deformation and cap stress is the mechanical behaviour of the diseased plaque components, of which little is known. The aim of this study is to determine material properties of atherosclerotic plaques using a mixed experimental-numerical approach. Plaque deformation as measured ex-vivo with magnetic resonance imaging (MRI) will be matched with computed deformations based on the measured plaque geometry.
CFD Challenge: Application of the Commercial Finite Element Solver FIDAP in a Clinical Setting
Authors: Cibis Merih , Wentzel Jolanda J. , Gijsen Frank J. H.
Published: July 2013

The Rotterdam group mainly focuses on the influence of shear stress on plaque localization and progression in human coronary and carotid arteries. Since we are in an academic hospital, we always have been working in close collaboration with cardiologists and radiologists. Since clinicians do not have the time or the sources that academic engineering groups have, we limited ourselves to perform the simulations on a standard desktop computer (Intel Xeon six core processor, 2.40 GHz CPU and 12 GB RAM) using commercial finite element software (FIDAP 8.7.4 with GAMBIT 2.4.6) within a reasonable time-frame (the weekend). The simulations were carried out by our PhD student Merih Cibis.
Next-Generation Techniques for Analysis of Lamina Cribrosa Microstructure
Authors: Ethier C. Ross , Abel Richie , Sander E. A. , Flanagan John G. , Girard Michael
Published: July 2013

Glaucoma describes a group of potentially blinding ocular disorders, afflicting c. 60 million people worldwide. Of these, c. 8 million are bilaterally blind, estimated to increase to 11 million by 2020. The central event in glaucoma is slow and irreversible damage of retinal ganglion cells, responsible for carrying visual information from the retina to the brain (Figure 1). Intraocular pressure (IOP) is a risk factor for glaucoma1–4, and significant, sustained IOP reduction is unequivocally beneficial in the clinical management of glaucoma patients2, 3, 5. Unfortunately, we do not understand how elevated IOP leads to the loss of retinal ganglion cells.
Patient-Specific Modeling and Hemodynamic Simulation in Healthy and Diseased Coronary Arteries
Authors: Itu Lucian , Sharma Puneet , Zheng Xudong , Mihalef Viorel , Kamen Ali , Suciu Constantin
Published: July 2013

Coronary Artery Disease is one of the leading causes of deaths worldwide, with an estimated 7.2 million deaths each year. In spite of the improvements in imaging and other diagnostic modalities, the incidence of premature morbidity and mortality is still very high, the main reason being the lack of accurate in-vivo and in-vitro patient-specific estimates for diagnosis and disease progression. Recently, CFD-based models have been proposed for analyzing the coronary circulation [1, 2]. The main challenges for such methods are the lack of patient-specific data (anatomy, boundary conditions), inefficient multi-scale coupling and computational resources. These challenges limit the scope of such methods in a routine clinical setting.
Cryomacroscopy in 3D: A Device Prototype for the Study of Cryopreservation
Authors: Rabin Yoed , Feig Justin S. G. , Williams Alexander C. , Lin Christopher C. , Thaokar Chandrajit
Published: July 2013

This study presents a new device prototype for visualization of physical effects associated with large-scale cryopreservation—the preservation of tissues at very low temperatures. Cryopreservation represents the only method for long-term preservation of biomaterials. While techniques for cryopreservation of single cells and small tissue structures are well established, cryopreservation techniques for bulky tissues and organs are still at the developmental stage. Critical to the success of cryopreservation is the control of ice formation—the cornerstone of cryoinjury. One of the most promising techniques for large-scale cryopreservation is known as vitrification, where the crystal phase is suppressed, and the biological material is trapped in a glassy-like state (vitreous in Latin means glassy) [1].
An In Vitro Study on Adjuvant Enhanced Irreversible Electroporation
Authors: Jiang Chunlan , Qin Zhenpeng , Long Gary , Bischof John C.
Published: July 2013

Recently, irreversible electroporation (IRE) has emerged as a promising tumor ablation technique. IRE induces cell death by irreversibly compromising membrane integrity with a series of short, high voltage electrical pulses [1]. IRE offers many advantages over surgery and thermal ablations including that it 1) is fast and minimally invasive, 2) destroys the tumor while preserving adjacent connective tissues [2], and 3) can be delivered with negligible thermal injury [3]. Here we hypothesize that the thresholds necessary to successfully electroporate cancer cell membranes, and therefore more effectively destroy an entire tumor, can be dramatically improved by careful choice of 1) electroporation parameter, and 2) chemical adjuvants that specifically impact the cell membrane.
Development of a Wearable Motion Analysis System for Evaluation and Rehabilitation of Mild Traumatic Brain Injury (mTBI)
Authors: Carey Stephanie L. , Hufford Kevin , Martori Amanda , Simoes Mario , Sinatra Francy , Dubey Rajiv V.
Published: July 2013

Mild traumatic brain injuries (mTBI) stem from a number of causes such as illnesses, strokes, accidents or battlefield traumas. These injuries can cause issues with everyday tasks, such as gait, and are linked with vestibular dysfunction [1]. Current technology that measures gait parameters often requires time consuming set up and post processing and is limited to the laboratory setting. The purpose of this study was to develop a wearable motion analysis system (WMAS) using five commercially available inertial measurement units (IMU) working in unison to record and output four gait parameters in a clinically relevant way. The WMAS has the potential to be used to 1) help diagnose mTBI or other neurocognitive disorders; 2) provide feedback to a clinician during a training session; 3) collect gait parameter data outside of the laboratory setting to determine rehabilitation progress; 4) provide quantitative outcome measures for rehabilitation efficacy.
CFD Challenge: Solutions Using an Open-Source Finite Volume Solver, OpenFOAM
Authors: Degroote Joris , Segers Patrick , Vierendeels Jan
Published: July 2013

The Institute Biomedical Technology and the Department of Flow, Heat and Combustion Mechanics of Ghent University have for more than a decade worked on the development and analysis of algorithms for the simulation of computational fluid dynamics (CFD) and fluid-structure interaction (FSI). These algorithms are applied to blood flow in large arteries, among others. For this Challenge, grid generation and CFD simulations have been performed by postdoctoral fellow Joris Degroote, using an open-source finite volume flow solver, OpenFOAM.
Extra-Fibrilar Matrix Properties of Human Annulus Fibrosus are Location and Age Dependent
Authors: Cortes Daniel H. , Han Woojin M. , Smith Lachlan J. , Elliott Dawn M.
Published: July 2013

Aging and degeneration of the intervertebral discs are cell mediated processes that include biochemical, mechanical and structural changes. Although these processes are similar, disc degeneration is defined as an accelerated aging process that results in a detriment in the function of the disc. Biochemical changes include protein cross-linking, proteoglycan depletion and changes on collagen type. These compositional changes are related to changes in the mechanical properties of the disc and its tissues. For instance, it has been shown that an increase of protein cross-linking by glycation or genipin treatment causes an increase of the stiffness in disc tissues [1,2]. On the other hand, a decrease on the amount of proteoglycan has been shown to cause a decrease on tissue stiffness due to a reduction of the osmotic pressure [3,4]. However, during aging and degeneration, these two processes occur simultaneously with opposing effects on the mechanical properties of the tissue. Consequently, it is important to analyze these effects separately. Additionally, many multiphasic models for soft charged tissues, such articular cartilage and intervertebral disc, also consider the ionic phases separately from non-charged solids. Although multiphasic models for the disc have been used in the past, the mechanical properties of the non-charged extra-fibrillar matrix (EFM) have not been measured directly.
Optofluidic Cytometry on a Chip
Authors: Hashemi Nastaran
Published: July 2013

The effects of global warming, pollution in river effluents, and changing ocean currents can be studied by characterizing variations in phytoplankton populations. We demonstrate the design and fabrication of a microflow cytometer for characterization of phytoplankton. Guided by chevron-shaped grooves on the top and bottom of a microfluidic channel, two symmetric sheath streams wrap around a central sample stream and hydrodynamically focus it in the center of the channel. The lasers are carefully chosen to provide excitation light close to the maximum absorbance wavelengths for the intrinsic fluorophores chlorophyll and phycoerythrin, and the excitation light is coupled to the flow cytometer through the use of an optical fiber. Fluorescence and light scatter are collected using two multimode optical fibers placed at 90-degree angles with respect to the excitation fiber. Light emerging from these collection fibers is directed through optical bandpass filters into photomultiplier tubes. The cytometer measured the optical and side scatter properties of Karenia b., Synechococcus sp., Pseudo-Nitzchia, Alexandrium, Nitzschia, and Thallassiosira pseudonana. The microflow cytometer proved sensitive enough to detect and characterize picoplankton with diameter approximately 1 μm and larger phytoplankton of up to 80 μm in length. The wide range in size discrimination coupled with detection of intrinsic fluorescent pigments suggests that this microflow cytometer will be able to distinguish different populations of phytoplankton on unmanned underwater vehicles. We also studied the effect of the sheath-to-sample flow-rate ratio on the light scatter and fluorescence of these marine microorganisms.
Effects of the Scleral Collagen Structure on the Biomechanical Response of the Optic Nerve Head
Authors: Coudrillier Baptiste , Boote Craig , Nguyen Thao D.
Published: July 2013

The sclera is a fiber-reinforced material composed of dense superimposed lamellae of type I collagen fibrils embedded in a matrix of elastin and proteoglycan. Recent Wide-Angle X-ray Scattering (WAXS) experiments (Meek, 2009) showed that the collagen lamellae are strongly aligned circumferentially in the region closest to the optic nerve head (ONH). The collagen structure was more disperse and heterogeneous away from the peripapillary region. The collagen structure of the sclera directly influences its material stiffness properties and therefore the level of strain transmitted to the tissues of the ONH, which is the primary site of damage in glaucoma. The effects of the fiber structure on the ONH biomechanics have been studied on the monkey eye (Girard, 2009), but not on the human eye. Recent work evaluating the influence of the human sclera on ONH biomechanics approximated the scleral behavior as linear elastic (Sigal, 2009) or hyperelastic orthotropic (Eilaghi, 2009).
Ex Vivo Blood Damage Measurement for an Intravascular Blood Cooling and Delivery System
Authors: Mingin Todd , Akers Jennifer A. , Merrill Denise R. , Chapman Benjamin E. , Jones Bernard , Merrill Thomas L.
Published: July 2013

An intravascular cooling system was developed to provide localized cooling directly to organs. Therapeutic hypothermia has been shown to reduce both ischemic and reperfusion injury related damage in both animal models and clinically for a range of organs including the heart, brain, and kidneys [1–4]. Cooling may ultimately aid in reducing damage from heart attack and stroke as well as problems associated with other organs.
Histology-Based, Lesion-Specific Modeling of Relative Stress Distributions Indicates Plaque Rupture Unlikely in Mice
Authors: Campbell Ian C. , Weiss Daiana , Virmani Renu , Vito Raymond P. , Oshinski John N. , Taylor W. Robert
Published: July 2013

Despite decades of research, atherosclerosis remains one of the leading killers in the modern world. Consequently, the atherosclerosis-prone mouse is frequently employed to study the pathophysiology of atherogenesis. To date, no investigator has conclusively observed natural plaque rupture in these commonly-studied strains. A likely explanation for the lack of observation of plaque rupture is that mouse plaques are morphologically different than human plaques and that the consequence of this difference is a solid mechanical environment in the mouse that is unlike that of humans. To investigate this possibility, we used finite element modeling based on histology specimens of mouse and human plaques to examine the spatial distribution of stresses within the walls of plaques in each organism.
Dynamic Tensile Loading and Altered Cell Contractility Modulate Nuclear Deformation and Cytoskeletal Connectivity
Authors: Driscoll Tristan P. , Heo Su-Jin , Mauck Robert L.
Published: July 2013

Effective use of progenitor cells in orthopaedic tissue engineering will require a thorough understanding of the mechanisms by which forces are transmitted and sensed, and how these change with differentiation. Nesprins are a family of structural proteins that partially localize to the nuclear envelope where they interact with both cytoskeletal and nucleoskeletal proteins [1]. At their C-terminus, nesprins interact through a KASH domain with proteins of the nuclear membrane, including SUN and Lamin A/C [1]. Multiple isoforms of the 4 nesprin genes are produced by alternative transcriptional initiation, translation and splicing. Specifically, nesprin 1 and nesprin 2 giant contain an N-terminal calponin homology domain (CH) that binds to and co-localizes with F-actin [2]. These nesprins are necessary for transmission of stress to the nucleus and are also differentially regulated with myogenesis, neurogenesis and adipogenesis [3,4]. We previously demonstrated that addition of TGF-3 induced nuclear Lamin A/C reorganization and nuclear stiffening in mesenchymal stem cells (MSCs), along with increased cell contractility and altered accumulation of smaller nesprin isoforms [5,6]. This study sought to determine the importance of contractility in transmission of force to the nucleus and the effect of dynamic loading on the expression of the giant nesprin isoforms.
Towards a Biomechanically-Based Diagnosis for Glaucoma: In Vivo Deformation Mapping of the Human Optic Nerve Head
Authors: Girard Michaël J. A. , Zimmo Lyn , White Edward T. , Mari Jean Martial , Ethier C. Ross , Strouthidis Nicholas G.
Published: July 2013

Glaucoma is the most common cause of irreversible blindness. It is associated with a progressive loss of cells within the optic nerve head (ONH) at the back of the eye. Glaucoma remains incurable and its exact causes are not well understood. It was once thought to occur only in eyes with elevated pressure (i.e., intraocular pressure or IOP) and to date, lowering IOP is the only clinical treatment proven to be beneficial for slowing the progression of glaucoma. However, the success rate of such therapy is only 50%. Multiple lines of evidence now indicate that IOP is not the only important risk factor in the disease. For instance, while some patients develop glaucoma at elevated IOP (high-tension glaucoma), some develop glaucoma at normal IOP levels (normal-tension glaucoma), and some others with elevated IOP do not develop glaucoma at all.
Predictions of Condylar Contact During Normal and Medial Thrust Gait
Authors: Manal Kurt , Buchanan Thomas S.
Published: July 2013

The medial compartment of the knee is the joint most often affected in those with osteoarthritis (OA). The knee adduction moment is a widely used surrogate measure of joint loading as direct measures are not possible except for a few individuals fitted with a force sensing prosthesis. A reduction in the frontal plane moment is believed to be associated with reduced joint compression. As such, treatments and/or gait alterations to reduce the magnitude of the adduction moment have been sought for those with knee OA. Walking with a medial thrust gait has been shown to reduce the magnitude of the knee adduction moment. The purpose of this paper is to apply our EMG-driven musculoskeletal model of the knee to predict muscle forces and condylar loading during normal and medial thrust gait for an individual fitted with an instrumented knee. It was anticipated that walking with a medial thrust gait would produce a reduced knee adduction moment. We propose however that a reduced knee adduction moment may not necessarily be associated with a decrease in medial compartment loading, and importantly, one must consider how the knee extensor moment changes before making inferences about joint loading.
In-Vivo Measurement of Vitreous Motion Using an Ultrasound Imaging Velocimetry Technique
Authors: Rossi Tommaso , Querzoli Giorgio , Repetto Rodolfo , Stocchino Alessandro , Pasqualitto Giacomo , Iossa Mario , Placentino Luca
Published: July 2013

Vitreous dynamics plays a fundamental role in the pathogenesis of various vitreo-retinal diseases, such as vitreous haemorrhage, peripheral retinal degeneration and tears, retinal detachment,… Quantitative measurement of vitreous motion has been attempted in the past using ultrasound imaging [1] and MRI [2]. However, information about vitreous motion secondary to eye rotations as well as knowledge of vitreous rheology is still limited.
Insulin and Ascorbate Have a Much Greater Influence Than Transferrin and Selenous Acid on the Growth of Engineered Cartilage in Chondrogenic Media
Authors: Cigan Alexander D. , Nims Robert J. , Albro Michael B. , Breves Sarah L. , Hung Clark T. , Ateshian Gerard A.
Published: July 2013

Tissue engineering of cartilage, which is a much sought-after approach for treatment of osteoarthritis and cartilage defects, requires appreciable culture time. Chemically defined chondrogenic media (CM) are commonly employed as they offer a promising alternative to serum-based media, and often include insulin, transferrin, and selenous acid (ITS) as well as ascorbate [1]. Concentrations of ITS constituents have been optimized based upon their ability to stimulate proliferation of a variety of cell types [2]. However, little is reflected in the literature as to the influences of various ITS constituent concentrations upon cartilage matrix deposition by chondrocytes. In engineered cartilage constructs that seek to match compositional and mechanical properties of native cartilage, knowledge of such influences would be highly desirable, especially when optimizing nutrient, hormone and vitamin supply for large constructs wherein rates of transport and consumption become more critical. Furthermore, this information would prove useful in modeling growth and remodeling of engineered tissues. Therefore, this study seeks to elucidate mechanical and biochemical properties as a direct result of modulating ITS and ascorbate concentrations within chondrocyte-agarose constructs.
Photoregulated Gene Expression in Human Cells With Light-Inducible Engineered Transcription Factors
Authors: Polstein Lauren R. , Gersbach Charles A.
Published: July 2013

Systems for controlling gene expression in mammalian cells have a wide range of applications in medicine, biotechnology and basic science. An ideal gene regulatory system would allow for precise and specific control over the magnitude and kinetics of gene expression in space and time, while also exerting minimal influence on other genes and cellular components. Several gene regulatory systems have been developed in which orthogonal transcription machinery from prokaryotes or insects has been imported into mammalian cells and used to control the expression of a specific gene. Despite the transformative impact of these systems in biomedical and biological research, several limitations of these technologies restrict the scope of possible applications. For example, gene expression in these systems is controlled by a freely diffusible small molecule, such as an antibiotic or steroid. Consequently, it is not possible to achieve spatial control over gene expression within cell culture, tissues, or whole organisms. This is in contrast to natural mechanisms of biological regulation in which spatial control is critical, such as developmental patterning and tissue morphogenesis. Second, dynamic gene regulation requires the removal of these small molecules, which may be slow, laborious, and/or impractical for a particular application. To overcome these limitations, we have engineered an optogenetic system in which the magnitude of gene expression in human cells can be finely tuned by photoregulated synthetic transcription factors.