Sample records for altered mechanical loading

  1. Evaluating Changes in Tendon Crimp with Fatigue Loading as an ex vivo Structural Assessment of Tendon Damage

    PubMed Central

    Freedman, Benjamin R.; Zuskov, Andrey; Sarver, Joseph J.; Buckley, Mark R.; Soslowsky, Louis J.

    2015-01-01

    The complex structure of tendons relates to their mechanical properties. Previous research has associated the waviness of collagen fibers (crimp) during quasi-static tensile loading to tensile mechanics, but less is known about the role of fatigue loading on crimp properties. In this study (IACUC approved), mouse patellar tendons were fatigue loaded while an integrated plane polariscope simultaneously assessed crimp properties. We demonstrate a novel structural mechanism whereby tendon crimp amplitude and frequency are altered with fatigue loading. In particular, fatigue loading increased the crimp amplitude across the tendon width and length, and these structural alterations were shown to be both region and load dependent. The change in crimp amplitude was strongly correlated to mechanical tissue laxity (defined as the ratio of displacement and gauge length relative to the first cycle of fatigue loading assessed at constant load throughout testing), at all loads and regions evaluated. Together, this study highlights the role of fatigue loading on tendon crimp properties as a function of load applied and region evaluated, and offers an additional structural mechanism for mechanical alterations that may lead to ultimate tendon failure. PMID:25773654

  2. Reduced Nucleus Pulposus Glycosaminoglycan Content Alters Intervertebral Disc Dynamic Viscoelastic Mechanics

    PubMed Central

    Boxberger, John I.; Orlansky, Amy S.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminglycan content alters dynamic mechanics. We hypothesized (1) that dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) that the disc would behave more elastically at higher frequencies, and finally, (3) that dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase-ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress. PMID:19539936

  3. Moderate tibia axial loading promotes discordant response of bone composition parameters and mechanical properties in a hindlimb unloading rat model.

    PubMed

    Yang, Peng-Fei; Huang, Ling-Wei; Nie, Xiao-Tong; Yang, Yue; Wang, Zhe; Ren, Li; Xu, Hui-Yun; Shang, Peng

    2018-06-01

    The purpose of the present study was to characterize the dynamic alterations of bone composition parameters and mechanical properties to disuse and mechanical intervention. A tail suspension hindlimb unloading model and an in vivo axial tibia loading model in rats were used. A moderate mechanical loading that was capable of engendering 800 µε tibia strain was applied to the right tibia of rats in both control and hindlimb unloading group across 28 days of the experimental period. The contralateral tibia served as control. Hindlimb unloading led to bone loss in tibia from day 14. Bone mineral density, mineral content and mechanical properties responded differently with microstructure to disuse in timing course. Mechanical loading of 800 µε tibia strain failed to alter the bone of the control group, but minimized the detrimental effects of unloading by completely prohibiting the decrease of bone mineral content and main mechanical properties after 28 days. Less obvious influence of mechanical loading on bone microstructure was found. The moderate mechanical loading is not able to stimulate the mechanical response of healthy tibia, but indeed lead to discordant recovery of bone composition parameters and mechanical properties.

  4. Security Policies for Mitigating the Risk of Load Altering Attacks on Smart Grid Systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ryutov, Tatyana; AlMajali, Anas; Neuman, Clifford

    2015-04-01

    While demand response programs implement energy efficiency and power quality objectives, they bring potential security threats to the Smart Grid. The ability to influence load in a system enables attackers to cause system failures and impacts the quality and integrity of power delivered to customers. This paper presents a security mechanism to monitor and control load according to a set of security policies during normal system operation. The mechanism monitors, detects, and responds to load altering attacks. We examined the security requirements of Smart Grid stakeholders and constructed a set of load control policies enforced by the mechanism. We implementedmore » a proof of concept prototype and tested it using the simulation environment. By enforcing the proposed policies in this prototype, the system is maintained in a safe state in the presence of load drop attacks.« less

  5. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis.

    PubMed

    Goldring, Mary B; Goldring, Steven R

    2010-03-01

    The articular surface plays an essential role in load transfer across the joint, and conditions that produce increased load transfer or altered patterns of load distribution accelerate the development of osteoarthritis (OA). Current knowledge segregates the risk factors into two fundamental mechanisms related to the adverse effects of "abnormal" loading on normal cartilage or "normal" loading on abnormal cartilage. Although chondrocytes can modulate their functional state in response to loading, their capacity to repair and modify the surrounding extracellular matrix is limited in comparison to skeletal cells in bone. This differential adaptive capacity underlies the more rapid appearance of detectable skeletal changes, especially after acute injuries that alter joint mechanics. The imbalance in the adaptation of the cartilage and bone disrupts the physiological relationship between these tissues and further contributes to OA pathology. This review focuses on the specific articular cartilage and skeletal features of OA and the putative mechanisms involved in their pathogenesis.

  6. An apparatus for altering the mechanical load of the respiratory system.

    PubMed

    Younes, M; Bilan, D; Jung, D; Kroker, H

    1987-06-01

    We describe an apparatus for altering the mechanical load against which the respiratory muscles operate in humans. A closed system incorporates a rolling seal spirometer. The spirometer piston shaft is coupled to a fast-responding linear actuator that develops force in proportion to desired command signals. The command signal may be flow (resistive loading or unloading), volume (elastic loading or unloading), constant voltage (continuous positive or negative pressure), or any external function. Combinations of loads can be applied. Logic circuits permit application of the load at specific times during the respiratory cycle, and the magnitude of the loads is continuously adjustable. Maximum pressure output is +/- 20 cmH2O. The apparatus permits loading or unloading over a range of ventilation extending from resting levels to those observed during high levels of exercise (over 100 l/min). In response to a square-wave input, pressure rises exponentially with a time constant of 20 ms.

  7. Compression Ratio Adjuster

    NASA Technical Reports Server (NTRS)

    Akkerman, J. W.

    1982-01-01

    New mechanism alters compression ratio of internal-combustion engine according to load so that engine operates at top fuel efficiency. Ordinary gasoline, diesel and gas engines with their fixed compression ratios are inefficient at partial load and at low-speed full load. Mechanism ensures engines operate as efficiently under these conditions as they do at highload and high speed.

  8. Effect of Age and Proteoglycan Deficiency on Collagen Fiber Re-Alignment and Mechanical Properties in Mouse Supraspinatus Tendon

    PubMed Central

    Connizzo, Brianne K.; Sarver, Joseph J.; Iozzo, Renato V.; Birk, David E.; Soslowsky, Louis J.

    2013-01-01

    Collagen fiber realignment is one mechanism by which tendon responds to load. Re-alignment is altered when the structure of tendon is altered, such as in the natural process of aging or with alterations of matrix proteins, such as proteoglycan expression. While changes in re-alignment and mechanical properties have been investigated recently during development, they have not been studied in (1) aged tendons, or (2) in the absence of key proteoglycans. Collagen fiber re-alignment and the corresponding mechanical properties are quantified throughout tensile mechanical testing in both the insertion site and the midsubstance of mouse supraspinatus tendons in wild type (WT), decorin-null (Dcn-/-), and biglycan-null (Bgn-/-) mice at three different ages (90 days, 300 days, and 570 days). Percent relaxation was significantly decreased with age in the WT and Dcn-/- tendons, but not in the Bgn-/- tendons. Changes with age were found in the linear modulus at the insertion site where the 300 day group was greater than the 90 day and 570 day group in the Bgn-/- tendons and the 90 day group was smaller than the 300 day and 570 day groups in the Dcn-/- tendons. However, no changes in modulus were found across age in WT tendons were found. The midsubstance fibers of the WT and Bgn-/- tendons were initially less aligned with increasing age. The re-alignment was significantly altered with age in the WT tendons, with older groups responding to load later in the mechanical test. This was also seen in the Dcn-/- midsubstance and the Bgn-/- insertion, but not in the other locations. Although some studies have found changes in the WT mechanical properties with age, this study did not support those findings. However, it did show fiber re-alignment changes at both locations with age, suggesting a breakdown of tendon′s ability to respond to load in later ages. In the proteoglycan-null tendons however, there were changes in the mechanical properties, accompanied only by location-dependent re-alignment changes, suggesting a site-specific role for these molecules in loading. Finally, changes in the mechanical properties did not occur in concert with changes in re-alignment, suggesting that typical mechanical property measurements alone are insufficient to describe how structural alterations affect tendon′s response to load. PMID:23445064

  9. Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

    ERIC Educational Resources Information Center

    Stevenson, Scott W.; Dudley, Gary A.

    2001-01-01

    Examined whether creatine (CR) monohydrate loading would alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with placebo loading in resistance-trained athletes. Overall, CR loading did not provide an ergogenic benefit for the unilateral dynamic knee extension…

  10. Diabetes Alters Mechanical Properties and Collagen Fiber Re-Alignment in Multiple Mouse Tendons

    PubMed Central

    Connizzo, Brianne K.; Bhatt, Pankti R.; Liechty, Kenneth W.; Soslowsky, Louis J.

    2014-01-01

    Tendons function to transfer load from muscle to bone through their complex composition and hierarchical structure, consisting mainly of type I collagen. Recent evidence suggests that type II diabetes may cause alterations in collagen structure, such as irregular fibril morphology and density, which could play a role in the mechanical function of tendons. Using the db/db mouse model of type II diabetes, the diabetic skin was found to have impaired biomechanical properties when compared to the non-diabetic group. The purpose of this study was to assess the effect of diabetes on biomechanics, collagen fiber re-alignment, and biochemistry in three functionally different tendons (Achilles, supraspinatus, patellar) using the db/db mouse model. Results showed that cross-sectional area and stiffness, but not modulus, were significantly reduced in all three tendons. However, the tendon response to load (transition strain, collagen fiber re-alignment) occurred earlier in the mechanical test, contrary to expectations. In addition, the patellar tendon had an altered response to diabetes when compared to the other two tendons, with no changes in fiber realignment and decreased collagen content at the midsubstance of the tendon. Overall, type II diabetes alters tendon mechanical properties and the dynamic response to load. PMID:24833253

  11. Altered sensory-motor control of the head as an etiological factor in space-motion sickness

    NASA Technical Reports Server (NTRS)

    Lackner, J. R.; DiZio, P.

    1989-01-01

    Mechanical unloading during head movements in weightlessness may be an etiological factor in space-motion sickness. We simulated altered head loading on Earth without affecting vestibular stimulation by having subjects wear a weighted helmet. Eight subjects were exposed to constant velocity rotation about a vertical axis with direction reversals every 60 sec. for eight reversals with the head loaded and eight with the head unloaded. The severity of motion sickness elicited was significantly higher when the head was loaded. This suggests that altered sensory-motor control of the head is also an etiological factor in space-motion sickness.

  12. Perceptual Load Alters Visual Excitability

    ERIC Educational Resources Information Center

    Carmel, David; Thorne, Jeremy D.; Rees, Geraint; Lavie, Nilli

    2011-01-01

    Increasing perceptual load reduces the processing of visual stimuli outside the focus of attention, but the mechanism underlying these effects remains unclear. Here we tested an account attributing the effects of perceptual load to modulations of visual cortex excitability. In contrast to stimulus competition accounts, which propose that load…

  13. Android Protection Mechanism: A Signed Code Security Mechanism for Smartphone Applications

    DTIC Science & Technology

    2011-03-01

    status registers, exceptions, endian support, unaligned access support, synchronization primitives , the Jazelle Extension, and saturated integer...supports comprehensive non-blocking shared-memory synchronization primitives that scale for multiple-processor system designs. This is an improvement... synchronization . Memory semaphores can be loaded and altered without interruption because the load and store operations are atomic. Processor

  14. Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice

    PubMed Central

    Wallace, Joseph M.; Golcuk, Kurtulus; Morris, Michael D.; Kohn, David H.

    2010-01-01

    Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which is independent of tissue quantity, suggests that deficiencies in tissue quality are responsible. However, the response to bgn-deficiency is inbred strain-specific. Mechanical loading influences bone matrix quality in addition to any increase in bone mass or change in bone formation activity. Since many diseases influence the mechanical integrity of bone through altered tissue quality, loading may be a way to prevent and treat extracellular matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response to mechanical loading vs. other inbred strains. It was therefore hypothesized that the bones from both wild type (WT) and KO B6;129 mice would be more responsive to exercise than the bones from C3H mice. To test these hypotheses at 11 weeks of age, following 21 consecutive days of exercise, we investigated cross-sectional geometry, mechanical properties, and tissue composition in the tibiae of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred strain-specific compositional and mechanical changes following exercise in WT and KO mice, and showed evidence of genotype-specific changes in bone in response to loading in a gene disruption model. This study further shows that exercise can influence bone tissue composition and/or mechanical integrity without changes in bone geometry. Together, these data suggest that exercise may represent a possible means to alter tissue quality and mechanical deficiencies caused by many diseases of bone. PMID:20033775

  15. The role of mechanical loading in ligament tissue engineering.

    PubMed

    Benhardt, Hugh A; Cosgriff-Hernandez, Elizabeth M

    2009-12-01

    Tissue-engineered ligaments have received growing interest as a promising alternative for ligament reconstruction when traditional transplants are unavailable or fail. Mechanical stimulation was recently identified as a critical component in engineering load-bearing tissues. It is well established that living tissue responds to altered loads through endogenous changes in cellular behavior, tissue organization, and bulk mechanical properties. Without the appropriate biomechanical cues, new tissue formation lacks the necessary collagenous organization and alignment for sufficient load-bearing capacity. Therefore, tissue engineers utilize mechanical conditioning to guide tissue remodeling and improve the performance of ligament grafts. This review provides a comparative analysis of the response of ligament and tendon fibroblasts to mechanical loading in current bioreactor studies. The differential effect of mechanical stimulation on cellular processes such as protease production, matrix protein synthesis, and cell proliferation is examined in the context of tissue engineering design.

  16. The Role of Mechanical Loading in Tendon Development, Maintenance, Injury, and Repair

    PubMed Central

    Galloway, Marc T.; Lalley, Andrea L.; Shearn, Jason T.

    2013-01-01

    ➤ Tendon injuries often result from excessive or insufficient mechanical loading, impairing the ability of the local tendon cell population to maintain normal tendon function. ➤ The resident cell population composing tendon tissue is mechanosensitive, given that the cells are able to alter the extracellular matrix in response to modifications of the local loading environment. ➤ Natural tendon healing is insufficient, characterized by improper collagen fibril diameter formation, collagen fibril distribution, and overall fibril misalignment. ➤ Current tendon repair rehabilitation protocols focus on implementing early, well-controlled eccentric loading exercises to improve repair outcome. ➤ Tissue engineers look toward incorporating mechanical loading regimens to precondition cell populations for the creation of improved biological augmentations for tendon repair. PMID:24005204

  17. THE ROLE OF MECHANOBIOLOGY IN TENDON HEALING

    PubMed Central

    Killian, Megan L.; Cavinatto, Leonardo; Galatz, Leesa M.; Thomopoulos, Stavros

    2011-01-01

    Mechanical cues affect tendon healing, homeostasis, and development in a variety of settings. Alterations in the mechanical environment are known to result in changes in the expression of extracellular matrix proteins, growth factors, transcription factors, and cytokines that can alter tendon structure and cell viability. Loss of muscle force in utero or in the immediate postnatal period delays tendon and enthesis development. The response of healing tendons to mechanical load varies depending on anatomic location. Flexor tendons require motion to prevent adhesion formation, yet excessive force results in gap formation and subsequent weakening of the repair. Excessive motion in the setting of anterior cruciate ligament reconstruction causes accumulation of macrophages, which are detrimental to tendon graft healing. Complete removal of load is detrimental to rotator cuff healing, yet large forces are also harmful. Controlled loading can enhance healing in most settings; however, a fine balance must be reached between loads that are too low (leading to a catabolic state) and too high (leading to micro-damage). This review will summarize existing knowledge of the mechanobiology of tendon development, homeostasis, and healing. PMID:22244066

  18. Microgravity Stress: Bone and Connective Tissue.

    PubMed

    Bloomfield, Susan A; Martinez, Daniel A; Boudreaux, Ramon D; Mantri, Anita V

    2016-03-15

    The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions. Copyright © 2016 John Wiley & Sons, Inc.

  19. Crack growth induced by thermal-mechanical loading

    NASA Astrophysics Data System (ADS)

    John, R.; Hartman, G. A.; Gallagher, J. P.

    1992-06-01

    Advanced aerospace structures are often subjected to combined thermal and mechanical loads. The fracture-mechanics behavior of the structures may be altered by the thermal state existing around the crack. Hence, design of critical structural elements requires the knowledge of stress-intensity factors under both thermal and mechanical loads. This paper describes the development of an experimental technique to verify the thermal-stress-intensity factor generated by a temperature gradient around the crack. Thin plate specimens of a model material (AISI-SAE 1095 steel) were used for the heat transfer and thermal-mechanical fracture tests. Rapid thermal loading was achieved using high-intensity focused infrared spot heaters. These heaters were also used to generate controlled temperature rates for heat-transfer verification tests. The experimental results indicate that thermal loads can generate stress-intensity factors large enough to induce crack growth. The proposed thermal-stress-intensity factors appear to have the same effect as the conventional mechanical-stress-intensity factors with respect to fracture.

  20. A micro-mechanical model to determine changes of collagen fibrils under cyclic loading

    NASA Astrophysics Data System (ADS)

    Chen, Michelle L.; Susilo, Monica E.; Ruberti, Jeffrey A.; Nguyen, Thao D.

    Dynamic mechanical loading induces growth and remodeling in biological tissues. It can alter the degradation rate and intrinsic mechanical properties of collagen through cellular activity. Experiments showed that repeated cyclic loading of a dense collagen fibril substrate increased collagen stiffness and strength, lengthened the substrate, but did not significantly change the fibril areal fraction or fibril anisotropy (Susilo, et al. ``Collagen Network Hardening Following Cyclic Tensile Loading'', Interface Focus, submitted). We developed a model for the collagen fibril substrate (Tonge, et al. ``A micromechanical modeling study of the mechanical stabilization of enzymatic degradation of collagen tissues'', Biophys J, in press.) to probe whether changes in the fibril morphology and mechanical properties can explain the tissue-level properties observed during cyclic loading. The fibrils were modeled as a continuous distribution of wavy elastica, based on experimental measurements of fibril density and collagen anisotropy, and can experience damage after a critical stress threshold. Other mechanical properties in the model were fit to the stress response measured before and after the extended cyclic loading to determine changes in the strength and stiffness of collagen fibrils.

  1. Influence of low glucose supply on the regulation of gene expression by nucleus pulposus cells and their responsiveness to mechanical loading.

    PubMed

    Rinkler, Christina; Heuer, Frank; Pedro, Maria Teresa; Mauer, Uwe Max; Ignatius, Anita; Neidlinger-Wilke, Cornelia

    2010-10-01

    Environmental alterations resulting in a decrease in the nutrient supply have been associated with intervertebral disc (IVD) degeneration, particularly of the nucleus pulposus (NP). The goal of the present study was to examine the hypothesis that glucose deprivation alters the metabolism of NP cells and their responsiveness to mechanical loading. A possible interaction of glucose supply and hydrostatic pressure (HP) with gene expression by NP cells has not been investigated. The influence of glucose supply (physiological concentration: 5 mM, reduction: 0 or 0.5 mM) and cyclic HP loading (2.5 MPa, 0.1 Hz, 30 minutes) on bovine and human NP cell matrix turnover was analyzed by quantitative real-time reverse transcriptase–polymerase chain reaction. Glucose-dependent effects on cell viability were determined by trypan blue exclusion. A glycosaminoglycan (GAG) assay was performed to determine nutritional effects on the protein level. Glucose reduction resulted in significant downregulations (p < 0.05) of aggrecan, collagen-I, and collagen-II gene expression by bovine NP cells. Exemplary human donors also displayed a similar trend for aggrecan and collagen-II, whereas matrix metalloproteinases (MMPs) tended to be upregulated under glucose deprivation. After HP loading, human NP cells showed individual upregulations of collagen-I and collagen-II expression, while MMP expression tended to be downregulated under glucose reduction relative to a normal glucose supply. Cell viability decreased with glucose deprivation. The GAG content was similar in all groups at Day 1, whereas at Day 3 there was a significant increase under physiological conditions. Glucose deprivation strongly affected NP cell metabolism. The effects of an altered glucose supply on gene expression were more pronounced than the mechanically induced effects. Data in this study demonstrate that the glucose environment is more critical for disc cell metabolism than mechanical loads. In individual human donors, however, adequate mechanical stimuli might have a beneficial effect on matrix turnover during IVD degeneration.

  2. Early life vitamin D depletion alters the postnatal response to skeletal loading in growing and mature bone

    PubMed Central

    Buckley, Harriet; Owen, Robert; Marin, Ana Campos; Lu, Yongtau; Eyles, Darryl; Lacroix, Damien; Reilly, Gwendolen C.; Skerry, Tim M.; Bishop, Nick J.

    2018-01-01

    There is increasing evidence of persistent effects of early life vitamin D exposure on later skeletal health; linking low levels in early life to smaller bone size in childhood as well as increased fracture risk later in adulthood, independently of later vitamin D status. A major determinant of bone mass acquisition across all ages is mechanical loading. We tested the hypothesis in an animal model system that early life vitamin D depletion results in abrogation of the response to mechanical loading, with consequent reduction in bone size, mass and strength during both childhood and adulthood. A murine model was created in which pregnant dams were either vitamin D deficient or replete, and their offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring were mechanically loaded and bone structure, extrinsic strength and growth measured both during growth and after skeletal maturity. Offspring of vitamin D deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone mass accrual in response to loading in both the growing skeleton and after skeletal maturity. Early life vitamin D depletion led to reduced bone strength and altered bone biomechanical properties. These findings suggest early life vitamin D status may, in part, determine the propensity to osteoporosis and fracture that blights later life in many individuals. PMID:29370213

  3. Hypertrophic gene expression induced by chronic stretch of excised mouse heart muscle.

    PubMed

    Raskin, Anna M; Hoshijima, Masahiko; Swanson, Eric; McCulloch, Andrew D; Omens, Jeffrey H

    2009-09-01

    Altered mechanical stress and strain in cardiac myocytes induce modifications in gene expression that affects cardiac remodeling and myocyte contractile function. To study the mechanisms of mechanotransduction in cardiomyocytes, probing alterations in mechanics and gene expression has been an effective strategy. However, previous studies are self-limited due to the general use of isolated neonatal rodent myocytes or intact animals. The main goal of this study was to develop a novel tissue culture chamber system for mouse myocardium that facilitates loading of cardiac tissue, while measuring tissue stress and deformation within a physiological environment. Intact mouse right ventricular papillary muscles were cultured in controlled conditions with superfusate at 95% O2/ 5% CO2, and 34 degrees C, such that cell to extracellular matrix adhesions as well as cell to cell adhesions were undisturbed and both passive and active mechanical properties were maintained without significant changes. The system was able to measure the induction of hypertrophic markers (BNP, ANP) in tissue after 2 hrs and 5 hrs of stretch. ANP induction was highly correlated with the diastolic load of the muscle but not with developed systolic load. Load induced ANP expression was blunted in muscles from muscle-LIM protein knockout mice, in which defective mechanotransduction pathways have been predicted.

  4. Observation of Failure and Domain Switching in Lead Zirconate Titanate Ceramics

    NASA Astrophysics Data System (ADS)

    Okayasu, Mitsuhiro; Sugiyama, Eriko; Sato, Kazuto; Mizuno, Mamoru

    The mechanical and electrical properties (electromechanical coupling coefficient, piezoelectric constant and dielectric constant) of lead zirconate titanate (PZT) ceramics are investigated during mechanical static and cyclic loading. There are several failure characteristics which can alter the material properties of PZT ceramics. The elastic constant increases and electrical properties decrease with increasing the applied load. This is due to the internal strain arising from the domain switching. In this case, 90° domain switching occurs anywhere in the samples as the sample is loaded. It is also apparent that electrogenesis occurs several times during cyclic loading to the final fracture. This occurrence is related to the domain switching. The elastic constant and electrical properties can decrease because of crack generation in the PZT ceramics. Moreover, the elastic constant increases with increase of the mechanical load and decreases with decrease of the load. On the contrary, the opposite sense of change of the electrical properties is observed.

  5. Role of Integrin in Mechanical Loading of Osteoblasts

    NASA Technical Reports Server (NTRS)

    Globus, Ruth; Demsky, Caroline

    2000-01-01

    Mechanical forces generated by gravity, weightbearing, and muscle contraction play a key role in the genesis and maintenance of skeletal structure. The molecular mechanisms that mediate changes in osteoblast activity in response to altered patterns of skeletal loading are not known, and a better understanding of these processes may be essential for developing effective treatment strategies to prevent disuse osteoporosis. We have elucidated specific integrin/ECM (extracellular matrix) interactions that are required for osteoblast differentiation and survival and have developed a useful loading system to further explore the molecular basis of mechano-sensitivity of osteoblasts. The long term goal of our collaborative research is to understand how the ECM and cell adhesion proteins and integrins interaction to mediate the response of osteoblasts and their progenitors to mechanical loading. We suggest that integrin/ECM interactions are crucial for basic cellular processes, including differentiation and survival, as well as to participate in detecting and mediating cellular responses to mechanical stimuli.

  6. Transcriptomics Profiling of Alzheimer’s Disease Reveal Neurovascular Defects, Altered Amyloid-β Homeostasis, and Deregulated Expression of Long Noncoding RNAs

    PubMed Central

    Magistri, Marco; Velmeshev, Dmitry; Makhmutova, Madina; Faghihi, Mohammad Ali

    2015-01-01

    Abstract The underlying genetic variations of late-onset Alzheimer’s disease (LOAD) cases remain largely unknown. A combination of genetic variations with variable penetrance and lifetime epigenetic factors may converge on transcriptomic alterations that drive LOAD pathological process. Transcriptome profiling using deep sequencing technology offers insight into common altered pathways regardless of underpinning genetic or epigenetic factors and thus represents an ideal tool to investigate molecular mechanisms related to the pathophysiology of LOAD. We performed directional RNA sequencing on high quality RNA samples extracted from hippocampi of LOAD and age-matched controls. We further validated our data using qRT-PCR on a larger set of postmortem brain tissues, confirming downregulation of the gene encoding substance P (TAC1) and upregulation of the gene encoding the plasminogen activator inhibitor-1 (SERPINE1). Pathway analysis indicates dysregulation in neural communication, cerebral vasculature, and amyloid-β clearance. Beside protein coding genes, we identified several annotated and non-annotated long noncoding RNAs that are differentially expressed in LOAD brain tissues, three of them are activity-dependent regulated and one is induced by Aβ1 - 42 exposure of human neural cells. Our data provide a comprehensive list of transcriptomics alterations in LOAD hippocampi and warrant holistic approach including both coding and non-coding RNAs in functional studies aimed to understand the pathophysiology of LOAD. PMID:26402107

  7. Load Carriage Induced Alterations of Pulmonary Function

    DTIC Science & Technology

    1989-01-01

    pulmonar , function reductions are directh’ related to the backpack load carried due to the mechanical constraint it imposes on the thoracic cage.2 To...and Fish- man. A.P.. 1965. The regulation of venttlation in diffuse Agostor. E.. D’Angelc, E. and Piolini, M., 1978. Breathing pulmonary fibrosis . J

  8. Energy cost and mechanical work of walking during load carriage in soldiers.

    PubMed

    Grenier, Jordane G; Peyrot, Nicolas; Castells, Josiane; Oullion, Roger; Messonnier, Laurent; Morin, Jean-Benoit

    2012-06-01

    In the military context, soldiers carry equipments of total mass often exceeding 30%-40% of their body mass (BM) and complexly distributed around their body (backpack, weapons, electronics, protections, etc.), which represents severe load carrying conditions. This study aimed to better understand the effects of load carriage on walking energetics and mechanics during military-type walking. Ten male infantrymen recently retired from the French Foreign Legion performed 3-min walking trials at a constant speed of 4 km·h(-1) on an instrumented treadmill, during which walking pattern spatiotemporal parameters, energy cost (C(W)), external mechanical work (W(ext)), and the work done by one leg against the other during the double-contact period (W(int,dc)) were specifically assessed. Three conditions were tested: (i) light sportswear (SP, reference condition considered as unloaded), (ii) battle equipment (BT, ∼22 kg, ∼27% of subjects' BM, corresponding to a military intermediate load), and (iii) road march equipment (RM, ∼38 kg, ∼46% of subjects' BM, corresponding to a military high load). Repeated-measures ANOVA showed that military equipment carriage significantly (i) altered the spatiotemporal pattern of walking (all P < 0.01), (ii) increased absolute gross and net CW (P < 0.0001), and (iii) increased both absolute and mass-relative W(ext) (P < 0.01) and W(int,dc) (P < 0.0001) but did not alter the inverted pendulum recovery or locomotor efficiency. Military equipments carriage induced significant changes in walking mechanics and energetics, but these effects appeared not greater than those reported with loads carried around the waist and close to the center of mass. This result was not expected because the latter has been hypothesized to be the optimal method of load carriage from a metabolic standpoint.

  9. FOOD WEB AND COMMUNITY COMPOSITION CHANGES IN RESPONSE TO NUTRIENT LOADING IN FRESHWATER AND MARINE COASTAL SYSTEMS (ESTUARIES AND COASTAL WETLANDS)

    EPA Science Inventory

    Our research will investigate the mechanisms by which increased loading of nutrients to coastal waters alters the structure and dynamics of food webs, resulting in declines in populations of ecologically and commercially important organisms. Research across NHEERL Divisions will...

  10. Computational characterization of fracture healing under reduced gravity loading conditions.

    PubMed

    Gadomski, Benjamin C; Lerner, Zachary F; Browning, Raymond C; Easley, Jeremiah T; Palmer, Ross H; Puttlitz, Christian M

    2016-07-01

    The literature is deficient with regard to how the localized mechanical environment of skeletal tissue is altered during reduced gravitational loading and how these alterations affect fracture healing. Thus, a finite element model of the ovine hindlimb was created to characterize the local mechanical environment responsible for the inhibited fracture healing observed under experimental simulated hypogravity conditions. Following convergence and verification studies, hydrostatic pressure and strain within a diaphyseal fracture of the metatarsus were evaluated for models under both 1 and 0.25 g loading environments and compared to results of a related in vivo study. Results of the study suggest that reductions in hydrostatic pressure and strain of the healing fracture for animals exposed to reduced gravitational loading conditions contributed to an inhibited healing process, with animals exposed to the simulated hypogravity environment subsequently initiating an intramembranous bone formation process rather than the typical endochondral ossification healing process experienced by animals healing in a 1 g gravitational environment. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1206-1215, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Alterations in gut transport of minerals and in binding proteins during simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Bikle, D. D.

    1984-01-01

    The structural components of the skeleton develop and are maintained in a 1 g environment, shaped by the mechanical load to which they are constantly exposed. Altering such a mechanical load by reducing the gravitational force imposed on the system, as in space flight, has profound effects on the skeleton and permits an exploration of the molecular events which regulate normal skeletal homeostasis. The objective was to determine whether simulated weightlessness reduced intestinal calcium transport, and if so, to determine the molecular mechanisms for such an effect. A nonstressful tail suspension in which the rats gained weight normally while suspended was used to simulate weightlessness. A significant change in intestinal calcium transport was not demonstrated. However, a cyclic change in bone formation with suspension was shown. Based on these observations, the objective changed to determination of the hormonal regulation of bone formation during simulated weightlessness.

  12. Features of lymphatic dysfunction in compressed skin tissues - Implications in pressure ulcer aetiology.

    PubMed

    Gray, Robert J; Voegeli, David; Bader, Dan L

    2016-02-01

    Impaired lymph formation and clearance has previously been proposed as a contributory factor in the development of pressure ulcers. The present study has been designed to trial fluorescence lymphangiography for establishing how lymphatic function is altered under a clinically relevant form of mechanical loading. Lymph formation and clearance was traced in both forearms by an intradermal injection of indocyanine green (ICG) (50 μl, 0.05%w/v), imaged using a commercial near-infrared fluorescence imaging unit (Fluobeam(®) 800). External uniaxial loading equivalent to a pressure of 60 mmHg was applied for 45 min in one arm using a custom-built indenter. Loading was associated with a decreased frequency of normal directional drainage (DD) of ICG within delineated vessels, both immediately after loading and 45 min thereafter. Loading was also associated with non-directional drainage (NDD) of ICG within the interstitium. Signal intensity within NDD was often greatest at areas of stress concentration, producing a 'halo pattern', corresponding to the rounded edges of the indenter. These results suggest that loading skin with a clinically relevant magnitude of pressure alters both lymph formation and clearance. Further work to quantify impaired clearance under mechanical loading could provide valuable insight into their involvement in the development of pressure ulcers. Copyright © 2016 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  13. Alterations in tendon microenvironment in response to mechanical load: potential molecular targets for treatment strategies

    PubMed Central

    Fouda, Mohamed B; Thankam, Finosh G; Dilisio, Matthew F; Agrawal, Devendra K

    2017-01-01

    Rotator cuff (RC) tendons could beinflicted in many ways with an eventual outcome of pain, weakness and disability, which represent a large burden on health care cost. However, optimal healing, either conservatively or with surgical intervention, remains an issue that needs further investigation. Disorders of the RC tendons may result from external factors like trauma, or internal factors through physiologic and metabolic derangement. Most RC tendon disorders may be asymptomatic and may result from an over-activity of the inflicted shoulder and its tendons. Such tendon disorders are poorly diagnosed since patients do not seek medical attention until pain or weakness ensue. Immunological and biochemical events in RC disorders due to mechanical intolerance have not been investigated. Generally, the mechanical load drives normal physiological properties of the tendon. But, mechanical overload/burden exerts stress on tenocytes, and disrupts the tendon microenvironment by triggering a multitude of signaling pathways leading to extracellular matrix remodeling, disorganization, alteration in collagen composition and apoptosis. These events result in weak tendon which is highly susceptible to rupture or tear. In this article, we critically reviewed the intrinsic signaling pathways that are excessively triggered by continuous mechanical load and the counteracting physiological responses and associated derangements. The elucidation of the molecular events underlying mechanical stress-induced symptomatic/asymptomatic tendinopathy could provide information on potential target sites for translational application in the management of rotator cuff disorders. PMID:29118899

  14. The effects of altered intrathoracic pressure on resting cerebral blood flow and its response to visual stimulation

    PubMed Central

    Hayen, Anja; Herigstad, Mari; Kelly, Michael; Okell, Thomas W.; Murphy, Kevin; Wise, Richard G.; Pattinson, Kyle T.S.

    2013-01-01

    Investigating how intrathoracic pressure changes affect cerebral blood flow (CBF) is important for a clear interpretation of neuroimaging data in patients with abnormal respiratory physiology, intensive care patients receiving mechanical ventilation and in research paradigms that manipulate intrathoracic pressure. Here, we investigated the effect of experimentally increased and decreased intrathoracic pressures upon CBF and the stimulus-evoked CBF response to visual stimulation. Twenty healthy volunteers received intermittent inspiratory and expiratory loads (plus or minus 9 cmH2O for 270 s) and viewed an intermittent 2 Hz flashing checkerboard, while maintaining stable end-tidal CO2. CBF was recorded with transcranial Doppler sonography (TCD) and whole-brain pseudo-continuous arterial spin labeling magnetic resonance imaging (PCASL MRI). Application of inspiratory loading (negative intrathoracic pressure) showed an increase in TCD-measured CBF of 4% and a PCASL-measured increase in grey matter CBF of 5%, but did not alter mean arterial pressure (MAP). Expiratory loading (positive intrathoracic pressure) did not alter CBF, while MAP increased by 3%. Neither loading condition altered the perfusion response to visual stimulation in the primary visual cortex. In both loading conditions localized CBF increases were observed in the somatosensory and motor cortices, and in the cerebellum. Altered intrathoracic pressures, whether induced experimentally, therapeutically or through a disease process, have possible significant effects on CBF and should be considered as a potential systematic confound in the interpretation of perfusion-based neuroimaging data. PMID:23108273

  15. Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load.

    PubMed

    Espinoza Orías, Alejandro A; Malhotra, Neil R; Elliott, Dawn M

    2009-03-01

    Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Cadaveric biomechanical study. Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081+/-0.026 (MPa/degrees, mean+/-SD) for lumbar axially loaded; 0.066+/-0.028 for caudal axially loaded; 0.091+/-0.033 for lumbar in pure torsion; and 0.056+/-0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/degrees. Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

  16. Rambling and trembling in response to body loading.

    PubMed

    Tahayor, Behdad; Riley, Zachary A; Mahmoudian, Armaghan; Koceja, David M; Hong, Siang Lee

    2012-04-01

    Various studies have suggested that postural sway is controlled by at least two subsystems. Rambling-Trembling analysis is a widely accepted methodology to dissociate the signals generated by these two hypothetical subsystems. The core assumption of this method is based on the equilibrium point hypothesis which suggests that the central nervous system preserves upright standing by transiently shifting the center of pressure (COP) from one equilibrium point to another. The trajectory generated by this shifting is referred to as rambling and its difference from the original COP signal is referred to as trembling. In this study we showed that these two components of COP are differentially affected when standing with external loads. Using Detrended Fluctuation analysis, we compared the pattern of these two signals in different configurations of body loading. Our findings suggest that by applying an external load, the dynamics of the trembling component is altered independently of the area of postural sway and also independently of the rambling component. The dynamics of rambling changed only during the backloading condition in which the postural sway area also substantially increased. It can be suggested that during loaded standing, the trembling mechanism (which is suggested to be activated by peripheral mechanisms and reflexes) is altered without affecting the central influence on the shifts of the equilibrium point.

  17. The effects of load carriage and muscle fatigue on lower-extremity joint mechanics.

    PubMed

    Wang, He; Frame, Jeff; Ozimek, Elicia; Leib, Daniel; Dugan, Eric L

    2013-09-01

    Military personnel are commonly afflicted by lower-extremity overuse injuries. Load carriage and muscular fatigue are major stressors during military basic training. To examine effects of load carriage and muscular fatigue on lower-extremity joint mechanics during walking. Eighteen men performed the following tasks: unloaded walking, walking with a 32-kg load, fatigued walking with a 32-kg load, and fatigued walking. After the second walking task, muscle fatigue was elicited through a fatiguing protocol consisting of metered step-ups and heel raises with a 16-kg load. Each walking task was performed at 1.67 m x s(-1) for 5 min. Walking movement was tracked by a VICON motion capture system at 120 Hz. Ground reaction forces were collected by a tandem force instrumented treadmill (AMTI) at 2,400 Hz. Lower-extremity joint mechanics were calculated in Visual 3D. There was no interaction between load carriage and fatigue on lower-extremity joint mechanics (p > .05). Both load carriage and fatigue led to pronounced alterations of lower-extremity joint mechanics (p < .05). Load carriage resulted in increases of pelvis anterior tilt, hip and knee flexion at heel contact, and increases of hip, knee, and ankle joint moments and powers during weight acceptance. Muscle fatigue led to decreases of ankle dorsiflexion at heel contact, dorsiflexor moment, and joint power at weight acceptance. In addition, muscle fatigue increased demand for hip extensor moment and power at weight acceptance. Statistically significant changes in lower-extremity joint mechanics during loaded and fatigued walking may expose military personnel to increased risk for overuse injuries.

  18. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

    NASA Technical Reports Server (NTRS)

    Westerlind, K. C.; Wronski, T. J.; Ritman, E. L.; Luo, Z. P.; An, K. N.; Bell, N. H.; Turner, R. T.

    1997-01-01

    Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

  19. Tissue adaptations to gravitational stress - Newborn versus adult giraffes

    NASA Technical Reports Server (NTRS)

    Hargens, Alan R; Gershuni, David H.; Danzig, Larry A.; Millard, Ronald W.; Pettersson, Knut

    1988-01-01

    Preliminary results on developmental alterations in load-bearing tissues of newborn and adult giraffes are presented. Attention is focused on vascular wall thickness in relation to local blood pressure, and on meniscal adaptations to increased load bearing in the developing giraffe. It is believed that the developing giraffe provides an excellent model for investigations of adaptive mechanisms of increased weight bearing.

  20. Effects of altered loading states on muscle plasticity: what have we learned from rodents?

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.

    1996-01-01

    This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

  1. The impact of substrate stiffness and mechanical loading on fibroblast-induced scaffold remodeling.

    PubMed

    Petersen, Ansgar; Joly, Pascal; Bergmann, Camilla; Korus, Gabriela; Duda, Georg N

    2012-09-01

    Fibroblasts as many other cells are known to form, contract, and remodel the extracellular matrix (ECM). The presented study aims to gain an insight into how mechanical boundary conditions affect the production of ECM components, their remodeling, and the feedback of the altered mechanical cell environment on these processes. The influence of cyclic mechanical loading (f=1 Hz, 10% axial compression) and scaffold stiffness (E=1.2 and 8.5 kPa) on the mechanical properties of fibroblast-seeded scaffold constructs were investigated in an in vitro approach over 14 days of culture. To do so, a newly developed bioreactor system was employed. While mechanical loading resulted in a clear upregulation of procollagen-I and fibronectin production, scaffold stiffness showed to primarily influence matrix metalloproteinase-1 (MMP-1) secretion and cell-induced scaffold contraction. Higher stiffness of the collagen scaffolds resulted in an up to twofold higher production of collagen-degrading MMP-1. The changes of mechanical parameters like Young's modulus, maximum compression force, and elastic portion of compression force over time suggest that from initially distinct mechanical starting conditions (scaffold stiffness), the construct's mechanical properties converge over time. As a consequence of mechanical loading a shift toward higher construct stiffness was observed. The results suggest that scaffold stiffness has only a temporary effect on cell behavior, while the impact of mechanical loading is preserved over time. Thus, it is concluded that the mechanical environment of the cell after remodeling is depending on mechanical loading rather than on initial scaffold stiffness.

  2. Rat Disc Torsional Mechanics: Effect of Lumbar and Caudal Levels and Axial Compression Load

    PubMed Central

    Elliott, Dawn M; Espinoza Orías, Alejandro A; Malhotra, Neil R

    2009-01-01

    Background Context Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior in order to evaluate changes following model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Purpose Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Study Design Cadaveric biomechanical study. Methods Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. Results The apparent torsional modulus was higher in the lumbar region than in the caudal region,: 0.081±0.026 (MPa/°, Mean±SD) for lumbar axially loaded; 0.066±0.028 caudal axially loaded; 0.091±0.033 for lumbar in pure torsion; and 0.056±0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/°. Conclusions Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics. PMID:18495544

  3. Deep Tissue Injury in Development of Pressure Ulcers: A Decrease of Inflammasome Activation and Changes in Human Skin Morphology in Response to Aging and Mechanical Load

    PubMed Central

    Stojadinovic, Olivera; Minkiewicz, Julia; Sawaya, Andrew; Bourne, Jonathan W.; Torzilli, Peter; de Rivero Vaccari, Juan Pablo; Dietrich, W. Dalton; Keane, Robert W.; Tomic-Canic, Marjana

    2013-01-01

    Molecular mechanisms leading to pressure ulcer development are scarce in spite of high mortality of patients. Development of pressure ulcers that is initially observed as deep tissue injury is multifactorial. We postulate that biomechanical forces and inflammasome activation, together with ischemia and aging, may play a role in pressure ulcer development. To test this we used a newly-developed bio-mechanical model in which ischemic young and aged human skin was subjected to a constant physiological compressive stress (load) of 300 kPa (determined by pressure plate analyses of a person in a reclining position) for 0.5–4 hours. Collagen orientation was assessed using polarized light, whereas inflammasome proteins were quantified by immunoblotting. Loaded skin showed marked changes in morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations and altered orientation of collagen fibers were observed in aged skin at earlier time points. Aged skin showed significant decreases in the levels of NLRP3 inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins expression in aged skin, whereas it significantly increased their levels in young skin. We conclude that aging contributes to rapid morphological changes and decrease in inflammasome proteins in response to tissue damage, suggesting that a decline in the innate inflammatory response in elderly skin could contribute to pressure ulcer pathogenesis. Observed morphological changes suggest that tissue damage upon loading may not be entirely preventable. Furthermore, newly developed model described here may be very useful in understanding the mechanisms of deep tissue injury that may lead towards development of pressure ulcers. PMID:23967056

  4. Effects of extreme-duration heavy load carriage on neuromuscular function and locomotion: a military-based study.

    PubMed

    Grenier, Jordane G; Millet, Guillaume Y; Peyrot, Nicolas; Samozino, Pierre; Oullion, Roger; Messonnier, Laurent; Morin, Jean-Benoît

    2012-01-01

    Trekking and military missions generally consist of carrying heavy loads for extreme durations. These factors have been separately shown to be sources of neuromuscular (NM) fatigue and locomotor alterations. However, the question of their combined effects remains unresolved, and addressing this issue required a representative context. The aim was to investigate the effects of extreme-duration heavy load carriage on NM function and walking characteristics. Ten experienced infantrymen performed a 21-h simulated military mission (SMM) in a middle-mountain environment with equipment weighing ∼27 kg during battles and ∼43 kg during marches. NM function was evaluated for knee extensors (KE) and plantar flexors (PF) pre- and immediately post-SMM using isometric maximal voluntary contraction (MVC) measurement, neural electrical stimulation and surface EMG. The twitch-interpolation method was used to assess central fatigue. Peripheral changes were examined by stimulating the muscle in the relaxed state. The energy cost, mechanical work and spatio-temporal pattern of walking were also evaluated pre-/post-SMM on an instrumented treadmill in three equipment conditions: Sportswear, Battle and March. After the SMM, MVC declined by -10.2±3.6% for KE (P<0.01) and -10.7±16.1% for PF (P = 0.06). The origin of fatigue was essentially peripheral for both muscle groups. A trend toward low-frequency fatigue was detected for KE (5.5%, P = 0.08). These moderate NM alterations were concomitant with a large increase in perceived fatigue from pre- (rating of 8.3±2.2) to post-SMM (15.9±2.1, P<0.01). The SMM-related fatigue did not alter walking energetics or mechanics, and the different equipment carried on the treadmill did not interact with this fatigue either. this study reports the first data on physiological and biomechanical consequences of extreme-duration heavy load carriage. Unexpectedly, NM function alterations due to the 21-h SMM were moderate and did not alter walking characteristics. Name: Effect of prolonged military exercises with high load carriage on neuromuscular fatigue and physiological/biomechanical responses. Number: NCT01127191.

  5. Effects of Extreme-Duration Heavy Load Carriage on Neuromuscular Function and Locomotion: A Military-Based Study

    PubMed Central

    Grenier, Jordane G.; Millet, Guillaume Y.; Peyrot, Nicolas; Samozino, Pierre; Oullion, Roger; Messonnier, Laurent; Morin, Jean-Benoît

    2012-01-01

    Trekking and military missions generally consist of carrying heavy loads for extreme durations. These factors have been separately shown to be sources of neuromuscular (NM) fatigue and locomotor alterations. However, the question of their combined effects remains unresolved, and addressing this issue required a representative context. Purpose The aim was to investigate the effects of extreme-duration heavy load carriage on NM function and walking characteristics. Methods Ten experienced infantrymen performed a 21-h simulated military mission (SMM) in a middle-mountain environment with equipment weighing ∼27 kg during battles and ∼43 kg during marches. NM function was evaluated for knee extensors (KE) and plantar flexors (PF) pre- and immediately post-SMM using isometric maximal voluntary contraction (MVC) measurement, neural electrical stimulation and surface EMG. The twitch-interpolation method was used to assess central fatigue. Peripheral changes were examined by stimulating the muscle in the relaxed state. The energy cost, mechanical work and spatio-temporal pattern of walking were also evaluated pre−/post-SMM on an instrumented treadmill in three equipment conditions: Sportswear, Battle and March. Results After the SMM, MVC declined by −10.2±3.6% for KE (P<0.01) and −10.7±16.1% for PF (P = 0.06). The origin of fatigue was essentially peripheral for both muscle groups. A trend toward low-frequency fatigue was detected for KE (5.5%, P = 0.08). These moderate NM alterations were concomitant with a large increase in perceived fatigue from pre- (rating of 8.3±2.2) to post-SMM (15.9±2.1, P<0.01). The SMM-related fatigue did not alter walking energetics or mechanics, and the different equipment carried on the treadmill did not interact with this fatigue either. Conclusion this study reports the first data on physiological and biomechanical consequences of extreme-duration heavy load carriage. Unexpectedly, NM function alterations due to the 21-h SMM were moderate and did not alter walking characteristics. Clinical Trial Registration Name: Effect of prolonged military exercises with high load carriage on neuromuscular fatigue and physiological/biomechanical responses. Number: NCT01127191. PMID:22927995

  6. Rotating electric machine with fluid supported parts

    DOEpatents

    Smith, Jr., Joseph L.; Kirtley, Jr., James L.

    1981-01-01

    A rotating electric machine in which the armature winding thereof and other parts are supported by a liquid to withstand the mechanical stresses applied during transient overloads and the like. In particular, a narrow gap is provided between the armature winding and the stator which supports it and this gap is filled with an externally pressurized viscous liquid. The liquid is externally pressurized sufficiently to balance the static loads on the armature winding. Transient mechanical loads which deform the armature winding alter the gap dimensions and thereby additionally pressurize the viscous liquid to oppose the armature winding deformation and more nearly uniformly to distribute the resulting mechanical stresses.

  7. Altered Tibiofemoral Joint Contact Mechanics and Kinematics in Patients with Knee Osteoarthritis and Episodic Complaints of Joint Instability

    PubMed Central

    Farrokhi, Shawn; Voycheck, Carrie A.; Klatt, Brian A.; Gustafson, Jonathan A.; Tashman, Scott; Fitzgerald, G. Kelley

    2014-01-01

    Background To evaluate knee joint contact mechanics and kinematics during the loading response phase of downhill gait in knee osteoarthritis patients with self-reported instability. Methods Forty-three subjects, 11 with medial compartment knee osteoarthritis and self-reported instability (unstable), 7 with medial compartment knee osteoarthritis but no reports of instability (stable), and 25 without knee osteoarthritis or instability (control) underwent Dynamic Stereo X-ray analysis during a downhill gait task on a treadmill. Findings The medial compartment contact point excursions were longer in the unstable group compared to the stable (p=0.046) and the control groups (p=0.016). The peak medial compartment contact point velocity was also greater for the unstable group compared to the stable (p=0.047) and control groups (p=0.022). Additionally, the unstable group demonstrated a coupled movement pattern of knee extension and external rotation after heel contact which was different than the coupled motion of knee flexion and internal rotation demonstrated by stable and control groups. Interpretation Our findings suggest that knee joint contact mechanics and kinematics are altered during the loading response phase of downhill gait in knee osteoarthritis patients with self-reported instability. The observed longer medial compartment contact point excursions and higher velocities represent objective signs of mechanical instability that may place the arthritic knee joint at increased risk for disease progression. Further research is indicated to explore the clinical relevance of altered contact mechanics and kinematics during other common daily activities and to assess the efficacy of rehabilitation programs to improve altered joint biomechanics in knee osteoarthritis patients with self-reported instability. PMID:24856791

  8. Mechanical load plays little role in contraction-mediated glucose transport in mouse skeletal muscle

    PubMed Central

    Sandström, Marie E; Zhang, Shi-Jin; Westerblad, Håkan; Katz, Abram

    2007-01-01

    The factors responsible for control of glucose transport during exercise are not fully understood. We investigated the role of mechanical load in contraction-mediated glucose transport in an isolated muscle preparation. Mouse extensor digitorum longus muscles were stimulated with repeated contractions for 10 min with or without N-benzyl-p-toluene sulphonamide (BTS, an inhibitor of myosin II ATPase) to block crossbridge activity. BTS inhibited force production during repeated contraction to ∼5% of control. In contrast, BTS had little effect on glucose transport in the basal state (control = 0.55 ± 0.04; BTS = 0.47 ± 0.09 μmol (20 min)−1 ml−1) or after contraction (control = 2.27 ± 0.15; BTS = 2.10 ± 0.16 μmol (20 min)−1 ml−1). BTS did not significantly alter the contraction-mediated changes in high-energy phosphates, glutathione status (a measure of oxidant status) or AMP-activated protein kinase activity. In conclusion, these data show that mechanical load plays little role in contraction-mediated glucose transport. Instead, it is likely that the increased glucose transport during contraction is a consequence of the increase in myoplasmic Ca2+ and the subsequent alterations in metabolism, e.g. increased energy turnover and production of reactive oxygen species. PMID:17185338

  9. Dynamic hydraulic fluid stimulation regulated intramedullary pressure.

    PubMed

    Hu, Minyi; Serra-Hsu, Frederick; Bethel, Neville; Lin, Liangjun; Ferreri, Suzanne; Cheng, Jiqi; Qin, Yi-Xian

    2013-11-01

    Physical signals within the bone, i.e. generated from mechanical loading, have the potential to initiate skeletal adaptation. Strong evidence has pointed to bone fluid flow (BFF) as a media between an external load and the bone cells, in which altered velocity and pressure can ultimately initiate the mechanotransduction and the remodeling process within the bone. Load-induced BFF can be altered by factors such as intramedullary pressure (ImP) and/or bone matrix strain, mediating bone adaptation. Previous studies have shown that BFF induced by ImP alone, with minimum bone strain, can initiate bone remodeling. However, identifying induced ImP dynamics and bone strain factor in vivo using a non-invasive method still remains challenging. To apply ImP as a means for alteration of BFF, it was hypothesized that non-invasive dynamic hydraulic stimulation (DHS) can induce local ImP with minimal bone strain to potentially elicit osteogenic adaptive responses via bone-muscle coupling. The goal of this study was to evaluate the immediate effects on local and distant ImP and strain in response to a range of loading frequencies using DHS. Simultaneous femoral and tibial ImP and bone strain values were measured in three 15-month-old female Sprague Dawley rats during DHS loading on the tibia with frequencies of 1Hz to 10Hz. DHS showed noticeable effects on ImP induction in the stimulated tibia in a nonlinear fashion in response to DHS over the range of loading frequencies, where they peaked at 2Hz. DHS at various loading frequencies generated minimal bone strain in the tibiae. Maximal bone strain measured at all loading frequencies was less than 8με. No detectable induction of ImP or bone strain was observed in the femur. This study suggested that oscillatory DHS may regulate the local fluid dynamics with minimal mechanical strain in the bone, which serves critically in bone adaptation. These results clearly implied DHS's potential as an effective, non-invasive intervention for osteopenia and osteoporosis treatments. © 2013. Published by Elsevier Inc. All rights reserved.

  10. Non-enzymatic glycation alters microdamage formation in human cancellous bone⋆

    PubMed Central

    Tang, S.Y.; Vashishth, D.

    2015-01-01

    Introduction The accumulation of advanced glycation end-products (AGEs) in bone has been suggested to adversely affect the fracture resistance of bone with aging, diabetes, and pharmacological treatments. The formation of AGEs increases crosslinking in the organic matrix of bone but it is unknown how elevated levels of AGEs affect the mechanisms of fracture resistance such as microdamage formation. Methods Human tibial cancellous bone cores were subjected to non-enzymatic glycation (NEG) by in vitro ribosylation and were mechanically loaded to pre- (0.6%) and post- (1.1%) yield apparent level strains. Loaded specimens were stained with lead–uranyl acetate and subjected to microCT-based 3D quantification and characterization of microdamage as either diffuse damage and linear microcracks. Damaged volume per bone volume (DV/BV) and damaged surface per damaged volume (DS/DV) ratios were used to quantify the volume and morphology of the detected microdamage, respectively. Results In vitro ribosylation increased the microdamage morphology parameter (DS/DV) under both pre-(p<0.05; +51%) and post-yield loading (p<0.001; +38%), indicating that the alteration of bone matrix by NEG caused the formation of crack-like microdamage morphologies. Under post-yield loading, the NEG-mediated increase in DS/DV was coupled with the reductions in microdamage formation (DV/BV; p<0.001) and toughness (p<0.001). Discussion Using a novel microCT technique to characterize and quantify microdamage, this study shows that the accumulation of AGEs in the bone matrix significantly alters the quantity and morphology of microdamage production and results in reduced fracture resistance. PMID:19747573

  11. Tendon biomechanics and mechanobiology - a mini-review of basic concepts and recent advancements

    PubMed Central

    Wang, James H-C.; Guo, Qianping; Li, Bin

    2011-01-01

    Due to their unique hierarchical structure and composition, tendons possess characteristic biomechanical properties, including high mechanical strength and viscoelasticity, which enable them to carry and transmit mechanical loads (muscular forces) effectively. Tendons are also mechano-responsive by adaptively changing their structure and function in response to altered mechanical loading conditions. In general, mechanical loading at physiological levels is beneficial to tendons, but excessive loading or disuse of tendons is detrimental. This mechano-adaptability is due to the cells present in tendons. Tendon fibroblasts (tenocytes) are the dominant tendon cells responsible for tendon homeostasis and repair. Tendon stem cells (TSCs), which were recently discovered, also play a vital role in tendon maintenance and repair by virtue of their ability to self-renew and differentiate into tenocytes. TSCs may also be responsible for chronic tendon injury, or tendinopathy, by undergoing aberrant differentiation into non-tenocytes in response to excessive mechanical loading. Thus, it is necessary to devise optimal rehabilitation protocols in order to enhance tendon healing while reducing scar tissue formation and tendon adhesions. Moreover, along with scaffolds that can mimic tendon matrix environments and platelet-rich plasma (PRP), which serves as a source of growth factors, TSCs may be the optimal cell type for enhancing repair of injured tendons. PMID:21925835

  12. Tendon biomechanics and mechanobiology--a minireview of basic concepts and recent advancements.

    PubMed

    Wang, James H-C; Guo, Qianping; Li, Bin

    2012-01-01

    Due to their unique hierarchical structure and composition, tendons possess characteristic biomechanical properties, including high mechanical strength and viscoelasticity, which enable them to carry and transmit mechanical loads (muscular forces) effectively. Tendons are also mechanoresponsive by adaptively changing their structure and function in response to altered mechanical loading conditions. In general, mechanical loading at physiological levels is beneficial to tendons, but excessive loading or disuse of tendons is detrimental. This mechanoadaptability is due to the cells present in tendons. Tendon fibroblasts (tenocytes) are the dominant tendon cells responsible for tendon homeostasis and repair. Tendon stem cells (TSCs), which were recently discovered, also play a vital role in tendon maintenance and repair by virtue of their ability to self-renew and differentiate into tenocytes. TSCs may also be responsible for chronic tendon injury, or tendinopathy, by undergoing aberrant differentiation into nontenocytes in response to excessive mechanical loading. Thus, it is necessary to devise optimal rehabilitation protocols to enhance tendon healing while reducing scar tissue formation and tendon adhesions. Moreover, along with scaffolds that can mimic tendon matrix environments and platelet-rich plasma, which serves as a source of growth factors, TSCs may be the optimal cell type for enhancing repair of injured tendons. Copyright © 2012 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

  13. The Effect of Mechanical Stimulation on Mineralization in Differentiating Osteoblasts in Collagen-I Scaffolds

    PubMed Central

    Damaraju, Swathi; Matyas, John R.; Rancourt, Derrick E.

    2014-01-01

    Developing a viable and functional bone scaffold in vitro that is capable of surviving and bearing mechanical load in vivo requires an understanding of the cell biology of osteoprogenitor cells, particularly how they are influenced by mechanical stimulation during cell differentiation and maturation. In this study, mechanical load was applied using a modified FlexCell plate to impart confined compression to collagen-I scaffolds seeded with undifferentiated murine embryonic stem cells. The activity, presence, and expression of osteoblast-cadherin (OB-Cad) and connexin-43, as well as various pluripotent and osteogenic markers were examined at 5–30 days of differentiation as cells were stimulated to differentiate to osteoblasts with and without applied mechanical load. Fluorescence recovery after photobleaching, immunofluorescence, viability, von Kossa, and real-time polymerase chain reaction assessments revealed that mechanical prestimulation of this cell-seeded scaffold altered the expression of OB-Cad and connexin-43 and resulted in significant differences in the structure and organization of mineralization present in the collagen matrix. Specifically, cells in gels that were loaded for 40 h after 5 days of differentiation and then left to fully differentiate for 30 days produced a highly structured honeycomb-shaped mineralization in the matrix; an outcome that was previously shown to be indicative of late osteoblast/early osteocyte activity. This study highlights the potential of mechanical load to accelerate differentiation and enhance osteoblast communication and function during the differentiation process, and highlights a time point of cell differentiation within this scaffold to apply load in order to most effectively transduce a mechanical signal. PMID:24851936

  14. Selected Contribution: Skeletal muscle focal adhesion kinase, paxillin, and serum response factor are loading dependent

    NASA Technical Reports Server (NTRS)

    Gordon, S. E.; Fluck, M.; Booth, F. W.

    2001-01-01

    This investigation examined the effect of mechanical loading state on focal adhesion kinase (FAK), paxillin, and serum response factor (SRF) in rat skeletal muscle. We found that FAK concentration and tyrosine phosphorylation, paxillin concentration, and SRF concentration are all lower in the lesser load-bearing fast-twitch plantaris and gastrocnemius muscles compared with the greater load-bearing slow-twitch soleus muscle. Of these three muscles, 7 days of mechanical unloading via tail suspension elicited a decrease in FAK tyrosine phosphorylation only in the soleus muscle and decreases in FAK and paxillin concentrations only in the plantaris and gastrocnemius muscles. Unloading decreased SRF concentration in all three muscles. Mechanical overloading (via bilateral gastrocnemius ablation) for 1 or 8 days increased FAK and paxillin concentrations in the soleus and plantaris muscles. Additionally, whereas FAK tyrosine phosphorylation and SRF concentration were increased by < or =1 day of overloading in the soleus muscle, these increases did not occur until somewhere between 1 and 8 days of overloading in the plantaris muscle. These data indicate that, in the skeletal muscles of rats, the focal adhesion complex proteins FAK and paxillin and the transcription factor SRF are generally modulated in association with the mechanical loading state of the muscle. However, the somewhat different patterns of adaptation of these proteins to altered loading in slow- vs. fast-twitch skeletal muscles indicate that the mechanisms and time course of adaptation may partly depend on the prior loading state of the muscle.

  15. The Effect of Tibial Plateau Levelling Osteotomy on Stifle Extensor Mechanism Load: A Canine Ex Vivo Study.

    PubMed

    Drew, Jarrod O; Glyde, Mark R; Hosgood, Giselle L; Hayes, Alex J

    2018-02-01

     To evaluate the effect of tibial plateau levelling osteotomy on stifle extensor mechanism load in an ex vivo cruciate-intact canine cadaveric model.   Ex vivo mechanical testing study.  Cadaveric canine pelvic limbs ( n  = 6).  A 21-mm tibial radial osteotomy was performed on pelvic limbs ( n  = 6) prior to being mounted into a load-bearing limb press. The proximal tibial segment was incrementally rotated until the anatomical tibial plateau angle had been rotated to at least 1°. The proportional change in stifle extensor mechanism load between the anatomical tibial plateau angle and the neutralized (∼6.5 degrees) and over-rotated (∼1°) tibial plateau angle was analysed using a one-sample t -test against a null hypothesis of no change. A p -value ≤0.05 was considered significant.  There was no significant change in the stifle extensor mechanism load from the anatomical tibial plateau angle (308 N [261-355 N]) to the neutralized tibial plateau angle (313 N [254-372 N]; p =.81), or from the anatomical tibial plateau angle to the over-rotated tibial plateau angle (303 N [254-352 N; p  = 0.67).  Tibial plateau levelling osteotomy does not significantly alter stifle extensor mechanism load at either a neutralized or over-rotated tibial plateau angle in our cruciate-intact model. Schattauer GmbH Stuttgart.

  16. Hydroclimatic and landscape controls on phosphorus loads to hypereutrophic Upper Klamath Lake, Oregon, United States

    NASA Astrophysics Data System (ADS)

    Records, R.; Fassnacht, S. R.; Arabi, M.; Duffy, W. G.

    2014-12-01

    Elevated total phosphorus (P) loading into Upper Klamath Lake, southern Oregon, United States has caused hypereutrophic conditions impacting endangered lake fish species. Increases in P loading have been attributed to land use changes, such as timber harvest and wetland drainage. The contribution of P to Upper Klamath Lake has been estimated from each major tributary, yet little research has explored what land use or other variables have most influence on P loading within the tributaries. In addition, previous work has shown a range of potential hydroclimatic shifts by the 2040s, with potential to alter P loading mechanisms. In this study, we use statistical methods including principle component analysis and multiple linear regression to determine what hydroclimatic and landscape variables best explain flow-weighted P concentration in the Sprague River, one of three main tributaries to Upper Klamath Lake. Identification of key variables affecting P loading has direct implications for management decisions in the Upper Klamath River Basin. Increases in P loading related to sediment loading are due to bank and upslope erosion. The former is more prevalent in areas of historic channel alteration and cattle grazing, while the latter is more dominant in areas of heavy timber harvesting and more precipitation as rain.

  17. Mechanical compression and hydrostatic pressure induce reversible changes in actin cytoskeletal organisation in chondrocytes in agarose.

    PubMed

    Knight, M M; Toyoda, T; Lee, D A; Bader, D L

    2006-01-01

    In numerous cell types, the cytoskeleton has been widely implicated in mechanotransduction pathways involving stretch-activated ion channels, integrins and deformation of intracellular organelles. Studies have also demonstrated that the cytoskeleton can undergo remodelling in response to mechanical stimuli such as tensile strain or fluid flow. In articular chondrocytes, the mechanotransduction pathways are complex, inter-related and as yet, poorly understood. Furthermore, little is known of how the chondrocyte cytoskeleton responds to physiological mechanical loading. This study utilises the well-characterised chondrocyte-agarose model and an established confocal image-analysis technique to demonstrate that both static and cyclic, compressive strain and hydrostatic pressure all induce remodelling of actin microfilaments. This remodelling was characterised by a change from a uniform to a more punctate distribution of cortical actin around the cell periphery. For some loading regimes, this remodelling was reversed over a subsequent 1h unloaded period. This reversible remodelling of actin cytoskeleton may therefore represent a mechanism through which the chondrocyte alters its mechanical properties and mechanosensitivity in response to physiological mechanical loading.

  18. Running stability is enhanced by a proximo-distal gradient in joint neuromechanical control.

    PubMed

    Daley, M A; Felix, G; Biewener, A A

    2007-02-01

    We currently know little about how animals achieve dynamic stability when running over uneven and unpredictable terrain, often characteristic of their natural environment. Here we investigate how limb and joint mechanics of an avian biped, the helmeted guinea fowl Numida meleagris, respond to an unexpected drop in terrain during running. In particular, we address how joint mechanics are coordinated to achieve whole limb dynamics. Based on muscle-tendon architecture and previous studies of steady and incline locomotion, we hypothesize a proximo-distal gradient in joint neuromechanical control. In this motor control strategy, (1) proximal muscles at the hip and knee joints are controlled primarily in a feedforward manner and exhibit load-insensitive mechanical performance, and (2) distal muscles at the ankle and tarsometatarso-phalangeal (TMP) joints are highly load-sensitive, due to intrinsic mechanical effects and rapid, higher gain proprioceptive feedback. Limb kinematics and kinetics during the unexpected perturbation reveal that limb retraction, controlled largely by the hip, remains similar to level running throughout the perturbed step, despite altered limb loading. Individual joints produce or absorb energy during both level and perturbed running steps, such that the net limb work depends on the balance of energy among the joints. The hip maintains the same mechanical role regardless of limb loading, whereas the ankle and TMP switch between spring-like or damping function depending on limb posture at ground contact. Initial knee angle sets limb posture and alters the balance of work among the joints, although the knee contributes little work itself. This distribution of joint function results in posture-dependent changes in work performance of the limb, which allow guinea fowl to rapidly produce or absorb energy in response to the perturbation. The results support the hypothesis that a proximo-distal gradient exists in limb neuromuscular performance and motor control. This control strategy allows limb cycling to remain constant, whereas limb posture, loading and energy performance are interdependent. We propose that this control strategy provides simple, rapid mechanisms for managing energy and controlling velocity when running over rough terrain.

  19. Running stability is enhanced by a proximo-distal gradient in joint neuromechanical control

    PubMed Central

    Daley, M. A.; Felix, G.; Biewener, A. A.

    2008-01-01

    Summary We currently know little about how animals achieve dynamic stability when running over uneven and unpredictable terrain, often characteristic of their natural environment. Here we investigate how limb and joint mechanics of an avian biped, the helmeted guinea fowl Numida meleagris, respond to an unexpected drop in terrain during running. In particular, we address how joint mechanics are coordinated to achieve whole limb dynamics. Based on muscle–tendon architecture and previous studies of steady and incline locomotion, we hypothesize a proximo-distal gradient in joint neuromechanical control. In this motor control strategy, (1) proximal muscles at the hip and knee joints are controlled primarily in a feedforward manner and exhibit load-insensitive mechanical performance, and (2) distal muscles at the ankle and tarsometatarso-phalangeal (TMP) joints are highly load-sensitive, due to intrinsic mechanical effects and rapid, higher gain proprioceptive feedback. Limb kinematics and kinetics during the unexpected perturbation reveal that limb retraction, controlled largely by the hip, remains similar to level running throughout the perturbed step, despite altered limb loading. Individual joints produce or absorb energy during both level and perturbed running steps, such that the net limb work depends on the balance of energy among the joints. The hip maintains the same mechanical role regardless of limb loading, whereas the ankle and TMP switch between spring-like or damping function depending on limb posture at ground contact. Initial knee angle sets limb posture and alters the balance of work among the joints, although the knee contributes little work itself. This distribution of joint function results in posture-dependent changes in work performance of the limb, which allow guinea fowl to rapidly produce or absorb energy in response to the perturbation. The results support the hypothesis that a proximo-distal gradient exists in limb neuromuscular performance and motor control. This control strategy allows limb cycling to remain constant, whereas limb posture, loading and energy performance are interdependent. We propose that this control strategy provides simple, rapid mechanisms for managing energy and controlling velocity when running over rough terrain. PMID:17234607

  20. Effects of Imbalanced Muscle Loading on Hip Joint Development and Maturation

    PubMed Central

    Ford, Caleb A.; Nowlan, Niamh C.; Thomopoulos, Stavros; Killian, Megan L.

    2017-01-01

    The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. PMID:27391299

  1. myo-Inositol 1,4,5-trisphosphate and Ca(2+)/calmodulin-dependent factors mediate transduction of compression-induced signals in bovine articular chondrocytes.

    PubMed Central

    Valhmu, Wilmot B; Raia, Frank J

    2002-01-01

    Although the effects of mechanical loading on chondrocyte metabolic activities have been extensively characterized, the sequence of events through which extracellular mechanical signals are transduced into chondrocytes and ultimately modulate cell activities is not well understood. Here, studies were performed to map out the sequential intracellular signalling pathways through which compression-induced signals modulate aggrecan mRNA levels in bovine articular chondrocytes. Bovine articular cartilage explants were subjected to a compressive stress of 0.1 MPa for 1 h in the presence or absence of inhibitors or antagonists of the phosphoinositol and Ca(2+)/calmodulin signalling pathways in order to determine the roles of second messengers and effector molecules of these pathways in transducing the compression-induced signals. In the absence of the inhibitors, aggrecan mRNA levels were stimulated by compression 2-4-fold relative to levels in tare-loaded (see below) explants. Treatment of the explants with graded levels of the protein kinase C inhibitor chelerythrine or bisindolylmaleimide I, followed by 1 h compressive loading, did not significantly alter the load-induced elevation of aggrecan mRNA levels. In contrast, thapsigargin, which depletes the Ins(1,4,5)P3-sensitive intracellular Ca(2+) stores, completely blocked the load response without significantly altering aggrecan mRNA levels in tare-loaded explants. Similarly, antagonists of the Ca(2+)/calmodulin signalling pathway dose-dependently or completely blocked the load-response. The results obtained demonstrate that transduction of the compression-induced aggrecan mRNA-regulating signals requires Ins(1,4,5)P3- and Ca(2+)/calmodulin-dependent signalling processes in bovine articular chondrocytes. PMID:11802800

  2. In vitro modeling of human tibial strains during exercise in micro-gravity

    NASA Technical Reports Server (NTRS)

    Peterman, M. M.; Hamel, A. J.; Cavanagh, P. R.; Piazza, S. J.; Sharkey, N. A.

    2001-01-01

    Prolonged exposure to micro-gravity causes substantial bone loss (Leblanc et al., Journal of Bone Mineral Research 11 (1996) S323) and treadmill exercise under gravity replacement loads (GRLs) has been advocated as a countermeasure. To date, the magnitudes of GRLs employed for locomotion in space have been substantially less than the loads imposed in the earthbound 1G environment, which may account for the poor performance of locomotion as an intervention. The success of future treadmill interventions will likely require GRLs of greater magnitude. It is widely held that mechanical tissue strain is an important intermediary signal in the transduction pathway linking the external loading environment to bone maintenance and functional adaptation; yet, to our knowledge, no data exist linking alterations in external skeletal loading to alterations in bone strain. In this preliminary study, we used unique cadaver simulations of micro-gravity locomotion to determine relationships between localized tibial bone strains and external loading as a means to better predict the efficacy of future exercise interventions proposed for bone maintenance on orbit. Bone strain magnitudes in the distal tibia were found to be linearly related to ground reaction force magnitude (R(2)>0.7). Strain distributions indicated that the primary mode of tibial loading was in bending, with little variation in the neutral axis over the stance phase of gait. The greatest strains, as well as the greatest strain sensitivity to altered external loading, occurred within the anterior crest and posterior aspect of the tibia, the sites furthest removed from the neutral axis of bending. We established a technique for estimating local strain magnitudes from external loads, and equations for predicting strain during simulated micro-gravity walking are presented.

  3. Dynamic Loading of Immature Epiphyseal Cartilage Pumps Nutrients out of Vascular Canals

    PubMed Central

    Albro, Michael B.; Banerjee, Rajan E.; Li, Roland; Oungoulian, Sevan R.; Chen, Bo; del Palomar, Amaya P.; Hung, Clark T.; Ateshian, Gerard A.

    2011-01-01

    The potential influence of mechanical loading on transvascular transport in vascularized soft tissues has not been explored extensively. This experimental investigation introduced and explored the hypothesis that dynamic mechanical loading can pump solutes out of blood vessels and into the surrounding tissue, leading to faster uptake and higher solute concentrations than could otherwise be achieved under unloaded conditions. Immature epiphyseal cartilage was used as a model tissue system, with fluorescein (332 Da), dextran (3, 10 and 70 kDa) and transferrin (80 kDa) as model solutes. Cartilage disks were either dynamically loaded (±10% compression over a 10% static offset strain, at 0.2 Hz) or maintained unloaded in solution for up to 20 hours. Results demonstrated statistically significant solute uptake in dynamically loaded (DL) explants relative to passive diffusion (PD) controls for all solutes except unbound fluorescein, as evidenced by the DL:PD concentration ratios after 20 hours (1.0 ± 0.2, 2.4 ± 1.1, 6.1 ± 3.3, 9.0 ± 4.0, and 5.5±1.6 for fluorescein, 3, 10, and 70 kDa dextran, and transferrin). Significant uptake enhancements were also observed within the first 30 seconds of loading. Termination of dynamic loading produced dissipation of enhanced solute uptake back to PD control values. Confocal images confirmed that solute uptake occurred from cartilage canals into their surrounding extracellular matrix. The incidence of this loading-induced transvascular solute pumping mechanism may significantly alter our understanding of the interaction of mechanical loading and tissue metabolism. PMID:21481875

  4. Mechanical signaling in the development of postmenopausal osteoporosis

    NASA Technical Reports Server (NTRS)

    Turner, R. T.

    1999-01-01

    Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

  5. Evaluation of nanostructural, mechanical, and biological properties of collagen-nanotube composites.

    PubMed

    Tan, Wei; Twomey, John; Guo, Dongjie; Madhavan, Krishna; Li, Min

    2010-06-01

    Collagen I is an essential structural and mechanical building block of various tissues, and it is often used as tissue-engineering scaffolds. However, collagen-based constructs reconstituted in vitro often lacks robust fiber structure, mechanical stability, and molecule binding capability. To enhance these performances, the present study developed 3-D collagen-nanotube composite constructs with two types of functionalized carbon nanotubes, carboxylated nanotubes and covalently functionalized nanotubes (CFNTs). The influences of nanotube functionalization and loading concentration on the collagen fiber structure, mechanical property, biocompatibility, and molecule binding were examined. Results revealed that surface modification and loading concentration of nanotubes determined the interactions between nanotubes and collagen fibrils, thus altering the structure and property of nanotube-collagen composites. Scanning electron microscopy and confocal microscopy revealed that the incorporation of CFNT in collagen-based constructs was an effective means of restructuring collagen fibrils because CFNT strongly bound to collagen molecules inducing the formation of larger fibril bundles. However, increased nanotube loading concentration caused the formation of denser fibril network and larger aggregates. Static stress-strain tests under compression showed that the addition of nanotube into collagen-based constructs did not significantly increase static compressive moduli. Creep/recovery testing under compression revealed that CFNT-collagen constructs showed improved mechanical stability under continuous loading. Testing with endothelial cells showed that biocompatibility was highly dependent on nanotube loading concentration. At a low loading level, CFNT-collagen showed higher endothelial coverage than the other tested constructs or materials. Additionally, CFNT-collagen showed capability of binding to other biomolecules to enhance the construct functionality. In conclusion, functionalized nanotube-collagen composites, particularly CFNT-collagen composites, could be promising materials, which provide structural support showing bundled fibril structure, biocompatibility, multifunctionality, and mechanical stability, but rigorous control over chemical modification, loading concentration, and nanotube dispersion are needed.

  6. Effects of imbalanced muscle loading on hip joint development and maturation.

    PubMed

    Ford, Caleb A; Nowlan, Niamh C; Thomopoulos, Stavros; Killian, Megan L

    2017-05-01

    The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either gluteal muscles or quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at postnatal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during postnatal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1128-1136, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. The Interaction of Surface Hydration and Vocal Loading on Voice Measures.

    PubMed

    Fujiki, Robert Brinton; Chapleau, Abigail; Sundarrajan, Anusha; McKenna, Victoria; Sivasankar, M Preeti

    2017-03-01

    Vocal loading tasks provide insight regarding the mechanisms underlying healthy laryngeal function. Determining the manner in which the larynx can most efficiently be loaded is a complex task. The goal of this study was to determine if vocal loading could be achieved in 30 minutes by altering phonatory mode. Owing to the fact that surface hydration facilitates efficient vocal fold oscillation, the effects of environmental humidity on vocal loading were also examined. This study also investigated whether the detrimental effects of vocal loading could be attenuated by increasing environmental humidity. Sixteen vocally healthy adults (8 men, 8 women) completed a 30-minute vocal loading task in low and moderate humidity. The order of humidities was counterbalanced across subjects. The vocal loading task consisted of reading with elevated pitch and pressed vocal quality and low pitch and pressed and/or raspy vocal quality in the presence of 65 dB ambient, multi-talker babble noise. Significant effects were observed for (1) cepstral peak prominence on soft sustained phonation at 10th and 80th pitches, (2) perceived phonatory effort, and (3) perceived tiredness ratings. No loading effects were observed for cepstral peak prominence on the rainbow passage, although fundamental frequency on the rainbow passage increased post loading. No main effect was observed for humidity. Following a 30-minute vocal loading task involving altering laryngeal vibratory mode in combination with increased volume. Also, moderate environmental humidity did not significantly attenuate the negative effects of loading. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  8. In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae.

    PubMed

    Ko, Frank C; Dragomir, Cecilia; Plumb, Darren A; Goldring, Steven R; Wright, Timothy M; Goldring, Mary B; van der Meulen, Marjolein C H

    2013-06-01

    Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone, and may subsequently influence the development of osteoarthritis (OA). Using an in vivo tibial loading model, the aim of this study was to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Cyclic compression at peak loads of 4.5N and 9.0N was applied to the left tibial knee joint of adult (26-week-old) C57BL/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. Changes in articular cartilage and subchondral bone were analyzed by histology and micro-computed tomography. Mechanical loading promoted cartilage damage in both age groups of mice, and the severity of joint damage increased with longer duration of loading. Metaphyseal bone mass increased with loading in young mice, but not in adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. In both age groups, articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau. Mice in both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. This noninvasive loading model permits dissection of temporal and topographic changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biologic events that promote OA onset and progression. Copyright © 2013 by the American College of Rheumatology.

  9. Aging Does Not Alter Tendon Mechanical Properties During Homeostasis, but does Impair Flexor Tendon Healing

    PubMed Central

    Ackerman, Jessica E.; Bah, Ibrahima; Jonason, Jennifer H.; Buckley, Mark R.; Loiselle, Alayna E.

    2017-01-01

    Aging is an important factor in disrupted homeostasis of many tissues. While an increased incidence of tendinopathy and tendon rupture are observed with aging, it is unclear whether this is due to progressive changes in tendon cell function and mechanics over time, or an impaired repair reaction from aged tendons in response to insult or injury. In the present study we examined changes in the mechanical properties of Flexor Digitorum Longus (FDL), Flexor Carpi Ulnaris (FCU), and tail fascicles in both male and female C57Bl/6 mice between 3-27 months of age to better understand the effects of sex and age on tendon homeostasis. No change in max load at failure was observed in any group over the course of aging, although there were significant decreases in toe and linear stiffness in female mice from 3-months to 15, and to 22-27-months. No changes in cell proliferation were observed with aging, although an observable decrease in cellularity occurred in 31-month old tendons. Given that aging did not dramatically alter tendon mechanical homeostasis we hypothesized that a disruption in tendon homeostasis, via acute injury would result in an impaired healing response. Significant decreases in max load, stiffness, and yield load were observed in repairs of 22-month old mice, relative to 4-month old mice. No changes in cell proliferation were observed between young and aged, however a dramatic loss of bridging collagen extracellular matrix was observed in aged repairs suggest that matrix production, but not cell proliferation leads to impaired tendon healing with aging. PMID:28419543

  10. The effects of load carriage on joint work at different running velocities.

    PubMed

    Liew, Bernard X W; Morris, Susan; Netto, Kevin

    2016-10-03

    Running with load carriage has become increasingly prevalent in sport, as well as many field-based occupations. However, the "sources" of mechanical work during load carriage running are not yet completely understood. The purpose of this study was to determine the influence of load magnitudes on the mechanical joint work during running, across different velocities. Thirty-one participants performed overground running at three load magnitudes (0%, 10%, 20% body weight), and at three velocities (3, 4, 5m/s). Three dimensional motion capture was performed, with synchronised force plate data captured. Inverse dynamics was used to quantify joint work in the stance phase of running. Joint work was normalized to a unit proportion of body weight and leg length (one dimensionless work unit=532.45J). Load significantly increased total joint work and total positive work and this effect was greater at faster velocities. Load carriage increased ankle positive work (β coefficient=rate of 6.95×10 -4 unit work per 1% BW carried), and knee positive (β=1.12×10 -3 unit) and negative work (β=-2.47×10 -4 unit), and hip negative work (β=-7.79×10 -4 unit). Load carriage reduced hip positive work and this effect was smaller at faster velocities. Inter-joint redistribution did not contribute significantly to altered mechanical work within the spectrum of load and velocity investigated. Hence, the ankle joint contributed to the greatest extent in work production, whilst that of the knee contributed to the greatest extent to work absorption when running with load. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds

    PubMed Central

    Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Doron-Faigenboim, Adi; Blumwald, Eduardo; Sadka, Avi

    2014-01-01

    Many fruit trees undergo cycles of heavy fruit load (ON-Crop) in one year, followed by low fruit load (OFF-Crop) the following year, a phenomenon known as alternate bearing (AB). The mechanism by which fruit load affects flowering induction during the following year (return bloom) is still unclear. Although not proven, it is commonly accepted that the fruit or an organ which senses fruit presence generates an inhibitory signal that moves into the bud and inhibits apical meristem transition. Indeed, fruit removal from ON-Crop trees (de-fruiting) induces return bloom. Identification of regulatory or metabolic processes modified in the bud in association with altered fruit load might shed light on the nature of the AB signalling process. The bud transcriptome of de-fruited citrus trees was compared with those of ON- and OFF-Crop trees. Fruit removal resulted in relatively rapid changes in global gene expression, including induction of photosynthetic genes and proteins. Altered regulatory mechanisms included abscisic acid (ABA) metabolism and auxin polar transport. Genes of ABA biosynthesis were induced; however, hormone analyses showed that the ABA level was reduced in OFF-Crop buds and in buds shortly following fruit removal. Additionally, genes associated with Ca2+-dependent auxin polar transport were remarkably induced in buds of OFF-Crop and de-fruited trees. Hormone analyses showed that auxin levels were reduced in these buds as compared with ON-Crop buds. In view of the auxin transport autoinhibition theory, the possibility that auxin distribution plays a role in determining bud fate is discussed. PMID:24706719

  12. Soldier occupational load carriage: a narrative review of associated injuries.

    PubMed

    Orr, Robin Marc; Pope, Rodney; Johnston, Venerina; Coyle, Julia

    2014-01-01

    This narrative review examines injuries sustained by soldiers undertaking occupational load carriage tasks. Military soldiers are required to carry increasingly heavier occupational loads. These loads have been found to increase the physiological cost to the soldier and alter their gait mechanics. Aggregated research findings suggest that the lower limbs are the most frequent anatomical site of injury associated with load carriage. While foot blisters are common, other prevalent lower limb injuries include stress fractures, knee and foot pain, and neuropathies, like digitalgia and meralgia. Shoulder neuropathies (brachial plexus palsy) and lower back injuries are not uncommon. Soldier occupational load carriage has the potential to cause injuries that impact on force generation and force sustainment. Through understanding the nature of these injuries targeted interventions, like improved physical conditioning and support to specialised organisations, can be employed.

  13. Temporomandibular joint fibrocartilage degeneration from unilateral dental splints.

    PubMed

    Henderson, Sarah E; Lowe, Jesse R; Tudares, Mauro A; Gold, Michael S; Almarza, Alejandro J

    2015-01-01

    The objective of this study was to determine the extent to which altered loading in the temporomandibular joint (TMJ), as might be associated with a malocclusion, drives degeneration of articulating surfaces in the TMJ. We therefore sought to quantify the effects of altered joint loading on the mechanical properties and biochemical content and distribution of TMJ fibrocartilage in the rabbit. Altered TMJ loading was induced with a 1mm splint placed unilaterally over the maxillary and mandibular molars for 6 weeks. At that time, TMJ fibrocartilage was assessed by compression testing, biochemical content (collagen, glycosaminoglycan (GAG), DNA) and distribution (histology), for both the TMJ disc and the condylar fibrocartilage. There were no changes in the TMJ disc for any of the parameters tested. The condylar fibrocartilage from the splinted animals was significantly stiffer and the DNA content was significantly lower than that in control animals. There was significant remodeling in the condylar fibrocartilage layers as manifested by a change in GAG and collagen II distribution and a loss of defined cell layers. A connection between the compressive properties of TMJ condylar fibrocartilage after 6 weeks of splinting and the changes in histology was observed. These results suggest a change in joint loading leads to condylar damage, which may contribute to pain associated with at least some forms of TMJ disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Temporomandibular Joint Fibrocartilage Degeneration from Unilateral Dental Splints

    PubMed Central

    Henderson, Sarah E.; Lowe, Jesse R.; Tudares, Mauro A.; Gold, Michael S.; Almarza, Alejandro J.

    2014-01-01

    Objective The objective of this study was to determine the extent to which altered loading in the temporomandibular joint (TMJ), as might be associated with a maloclussion, drives degeneration of articulating surfaces in the TMJ. We therefore sought to quantify the effects of altered joint loading on the mechanical properties and biochemical content and distribution of TMJ fibrocartilage in the rabbit. Design Altered TMJ loading was induced with a 1 mm splint placed unilaterally over the maxillary and mandibular molars for six weeks. At that time, TMJ fibrocartilage was assessed by compression testing, biochemical content (collagen, glycosaminoglycan (GAG), DNA) and distribution (histology), for both the TMJ disc and the condylar fibrocartilage. Results There were no changes in the TMJ disc for any of the parameters tested. The condylar fibrocartilage from the splinted animals was significantly stiffer and the DNA content was significantly lower than that in control animals. There was significant remodeling in the condylar fibrocartilage layers as manifested by a change in GAG and collagen II distribution and a loss of defined cell layers. Conclusions A connection between the compressive properties of TMJ condylar fibrocartilage after 6 weeks of splinting and the changes in histology was observed. These results suggest a change in joint loading, leads to condylar damage, which may contribute to pain associated with at least some forms of TMJ disease. PMID:25247778

  15. Gravitational loading of a simulated launch alters mRNA expression in osteoblasts

    NASA Technical Reports Server (NTRS)

    Fitzgerald, J.; Hughes-Fulford, M.

    1996-01-01

    Serum-deprived mouse osteoblastic cells (MC3T3-E1a) were centrifuged under a regime designed to simulate a space shuttle launch (maximum of 3g). Messenger RNA levels for eight genes involved in bone growth and maintenance were determined using RT-PCR. Following 30 min of centrifugation, mRNA level for early response gene c-fos was significantly increased 89% (P < 0.05). The c-fos induction was transient and returned to control levels after 3 h. The mRNA level for the mineralization marker gene osteocalcin was significantly decreased to 44% of control level (P < 0.005) 3 h after centrifugation. No changes in mRNA levels were detected for c-myc, TGFbeta1, TGFbeta2, cyclophilin A, or actin. No basal mRNA level for TGFbeta3 was detected. In addition, no change in the steady-state synthesis of prostaglandin E2 was detected, possibly due to lack of lipid substrates in serum-deprived cells, suggesting that the increase in c-fos mRNA in response to gravitational loading is a result of mechanical stimulation. These results indicate that a small magnitude mechanical loading, such as that experienced during a shuttle launch, can alter mRNA levels in quiescent osteoblastic cells.

  16. The mechanics of the primary cilium: an intricate structure with complex function.

    PubMed

    Hoey, David A; Downs, Matthew E; Jacobs, Christopher R

    2012-01-03

    The primary cilium is a non-motile singular cellular structure that extends from the surface of nearly every cell in the body. The cilium has been shown to play numerous roles in maintaining tissue homeostasis, through regulating signaling pathways and sensing both biophysical and biochemical changes in the extracellular environment. The structural performance of the cilium is paramount to its function as defective cilia have been linked to numerous pathologies. In particular, the cilium has demonstrated a mechanosensory role in tissues such as the kidney, liver, endothelium and bone, where cilium deflection under mechanical loading triggers a cellular response. Understanding of how cilium structure and subsequent mechanical behavior contributes to the roles that cilium plays in regulating cellular behavior is a compelling question, yet is a relatively untouched research area. Recent advances in biophysical measurements have demonstrated the cilium to be a structurally intricate organelle containing an array of load bearing proteins. Furthermore advances in modeling of this organelle have revealed the importance of these proteins at regulating the cilium's mechanosensitivity. Remarkably, the cilium is capable of adapting its mechanical state, altering its length and possibly it's bending resistance, to regulate its mechanosensitivity demonstrating the importance of cilium mechanics in cellular responses. In this review, we introduce the cilium as a mechanosensor; discuss the advances in the mechanical modeling of cilia; explore the structural features of the cilium, which contribute to its mechanics and finish with possible mechanisms in which alteration in structure may affect ciliary mechanics, consequently affecting ciliary based mechanosensing. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. On mechanical mechanism of damage evolution in articular cartilage.

    PubMed

    Men, Yu-Tao; Jiang, Yan-Long; Chen, Ling; Zhang, Chun-Qiu; Ye, Jin-Duo

    2017-09-01

    Superficial lesions of cartilage are the direct indication of osteoarthritis. To investigate the mechanical mechanism of cartilage with micro-defect under external loading, a new plain strain numerical model with micro-defect was proposed and damage evolution progression in cartilage over time has been simulated, the parameter were studied including load style, velocity of load and degree of damage. The new model consists of the hierarchical structure of cartilage and depth-dependent arched fibers. The numerical results have shown that not only damage of the cartilage altered the distribution of the stress but also matrix and fiber had distinct roles in affecting cartilage damage, and damage in either matrix or fiber could promote each other. It has been found that the superficial cracks in cartilage spread preferentially along the tangent direction of the fibers. It is the arched distribution form of fibers that affects the crack spread of cartilage, which has been verified by experiment. During the process of damage evolution, its extension direction and velocity varied constantly with the damage degree. The rolling load could cause larger stress and strain than sliding load. Strain values of the matrix initially increased and then decreased gradually with the increase of velocity, and velocity had a greater effect on matrix than fibers. Damage increased steadily before reaching 50%, sharply within 50 to 85%, and smoothly and slowly after 85%. The finding of the paper may help to understand the mechanical mechanism why the cracks in cartilage spread preferentially along the tangent direction of the fibers. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Skeletal adaptation to intramedullary pressure-induced interstitial fluid flow is enhanced in mice subjected to targeted osteocyte ablation.

    PubMed

    Kwon, Ronald Y; Meays, Diana R; Meilan, Alexander S; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A

    2012-01-01

    Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF.

  19. Parathyroid hormone modulates the response of osteoblast-like cells to mechanical stimulation

    NASA Technical Reports Server (NTRS)

    Ryder, K. D.; Duncan, R. L.

    2000-01-01

    Mechanical loading stimulates many responses in bone and osteoblasts associated with osteogenesis. Since loading and parathyroid hormone (PTH) activate similar signaling pathways in osteoblasts, we postulate that PTH can potentiate the effects of mechanical stimulation. Using an in vitro four-point bending device, we found that expression of COX-2, the inducible isoform of cyclooxygenase, was dependent on fluid forces generated across the culture plate, but not physiologic levels of strain in MC3T3-E1 osteoblast-like cells. Addition of 50 nM PTH during loading increased COX-2 expression at both subthreshold and threshold levels of fluid forces compared with either stimuli alone. We also demonstrated that application of fluid shear to MC3T3-E1 cells induced a rapid increase in [Ca(2+)](i). Although PTH did not significantly change [Ca(2+)](i) levels, flow and PTH did produce a significantly greater [Ca(2+)](i) response and increased the number of responding cells than is found in fluid shear alone. The [Ca(2+)](i) response to these stimuli was significantly decreased when the mechanosensitive channel inhibitor, gadolinium, was present. These studies indicate that PTH increases the cellular responses of osteoblasts to mechanical loading. Furthermore, this response may be mediated by alterations in [Ca(2+)](i) by modulating the mechanosensitive channel.

  20. Physiological pump loading of isolated cardiac muscle.

    PubMed

    Paulus, W J; Claes, V A; Brutsaert, D L

    1976-05-01

    Cat papillary muscles were subjected to a continuously changing load, resulting from an analysis of the left ventricle as a muscle pump system. The papillary muscle was assumed to be part of a circumferential bundle of muscle fibers of a simplified ejecting ventricle. The load included the pressure--stress relationship of this ventricle and the peripheral vascular load with its inertial, resistive and capacitive components. When this loading function was imposed on a shortening muscle through an electronic feedback circuit, the time course of force development and the velocity versus force plots closely resembled data obtained in the intact heart. Analysis of mechanical work (delta 1 X f) and power (V X f) and their respective time course permitted distinction between changes of contractile performance due to (1) positive or negative inotropic interventions, (2) altered hypothetical ventricular dimensions and changed preload, and (3) the long-term load-dependent memory of cardiac muscle.

  1. Chronic In Vivo Load Alteration Induces Degenerative Changes in the Rat Tibiofemoral Joint

    PubMed Central

    Roemhildt, M. L.; Beynnon, B. D.; Gauthier, A. E.; Gardner-Morse, M.; Ertem, F.; Badger, G. J.

    2012-01-01

    Objective We investigated the relationship between the magnitude and duration of sustained compressive load alteration and the development of degenerative changes in the rat tibiofemoral joint. Methods A varus loading device was attached to the left hind limb of mature rats to apply increased compression to the medial compartment and decreased compression to the lateral compartment of the tibiofemoral joint of either 0% or 100% body weight for 0, 6 or 20 weeks. Compartment-specific assessment of the tibial plateaus included biomechanical measures (articular cartilage aggregate modulus, permeability and Poisson’s ratio, and subchondral bone modulus) and histological assessments (articular cartilage, calcified cartilage, and subchondral bone thicknesses, degenerative scoring parameters, and articular cartilage cellularity). Results Increased compression in the medial compartment produced significant degenerative changes consistent with the development of osteoarthritis including a progressive decrease in cartilage aggregate modulus (43% and 77% at 6 and 20 weeks), diminished cellularity (38% and 51% at 6 and 20 weeks), and increased histological degeneration. At 20 weeks, medial compartment articular cartilage thickness deceased 30% while subchondral bone thickness increased 32% and subchondral bone modulus increased 99%. Decreased compression in the lateral compartment increased calcified cartilage thickness, diminished region-specific subchondral bone thickness and revealed trends for reduced cellularity and decreased articular cartilage thickness at 20 weeks. Conclusions Altered chronic joint loading produced degenerative changes consistent with those observed clinically with the development of osteoarthritis and may replicate the slow development of non-traumatic osteoarthritis in which mechanical loads play a primary etiological role. PMID:23123358

  2. Honeycomb chassis for electronic components

    NASA Technical Reports Server (NTRS)

    Read, W. S.; Stebbins, B. W.

    1977-01-01

    In new electronic chassis support, machined honeycomb members are used to change basic relationship between chassis and support structure. Improved chassis combines internal and external support and heat dissipation by altering chassis internal geometry. Honeycomb materials allow mechanical support and thermal load sharing to be combined at lower weight and lower cost than previous equipment.

  3. Nitrogen enrichment suppresses other environmental drivers and homogenizes salt marsh leaf microbiome

    DOE PAGES

    Daleo, Pedro; Alberti, Juan; Jumpponen, Ari; ...

    2018-04-12

    Microbial community assembly is affected by a combination of forces that act simultaneously, but the mechanisms underpinning their relative influences remain elusive. This gap strongly limits our ability to predict human impacts on microbial communities and the processes they regulate. Here, we experimentally demonstrate that increased salinity stress, food web alteration and nutrient loading interact to drive outcomes in salt marsh fungal leaf communities. Both salinity stress and food web alterations drove communities to deterministically diverge, resulting in distinct fungal communities. Increased nutrient loads, nevertheless, partially suppressed the influence of other factors as determinants of fungal assembly. Using a nullmore » model approach, we found that increased nutrient loads enhanced the relative importance of stochastic over deterministic divergent processes; without increased nutrient loads, samples from different treatments showed a relatively (deterministic) divergent community assembly whereas increased nutrient loads drove the system to more stochastic assemblies, suppressing the effect of other treatments. These results demonstrate that common anthropogenic modifications can interact to control fungal community assembly. As a result, our results suggest that when the environmental conditions are spatially heterogeneous (as in our case, caused by specific combinations of experimental treatments), increased stochasticity caused by greater nutrient inputs can reduce the importance of deterministic filters that otherwise caused divergence, thus driving to microbial community homogenization.« less

  4. Nitrogen enrichment suppresses other environmental drivers and homogenizes salt marsh leaf microbiome.

    PubMed

    Daleo, Pedro; Alberti, Juan; Jumpponen, Ari; Veach, Allison; Ialonardi, Florencia; Iribarne, Oscar; Silliman, Brian

    2018-06-01

    Microbial community assembly is affected by a combination of forces that act simultaneously, but the mechanisms underpinning their relative influences remain elusive. This gap strongly limits our ability to predict human impacts on microbial communities and the processes they regulate. Here, we experimentally demonstrate that increased salinity stress, food web alteration and nutrient loading interact to drive outcomes in salt marsh fungal leaf communities. Both salinity stress and food web alterations drove communities to deterministically diverge, resulting in distinct fungal communities. Increased nutrient loads, nevertheless, partially suppressed the influence of other factors as determinants of fungal assembly. Using a null model approach, we found that increased nutrient loads enhanced the relative importance of stochastic over deterministic divergent processes; without increased nutrient loads, samples from different treatments showed a relatively (deterministic) divergent community assembly whereas increased nutrient loads drove the system to more stochastic assemblies, suppressing the effect of other treatments. These results demonstrate that common anthropogenic modifications can interact to control fungal community assembly. Furthermore, our results suggest that when the environmental conditions are spatially heterogeneous (as in our case, caused by specific combinations of experimental treatments), increased stochasticity caused by greater nutrient inputs can reduce the importance of deterministic filters that otherwise caused divergence, thus driving to microbial community homogenization. © 2018 by the Ecological Society of America.

  5. Nitrogen enrichment suppresses other environmental drivers and homogenizes salt marsh leaf microbiome

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Daleo, Pedro; Alberti, Juan; Jumpponen, Ari

    Microbial community assembly is affected by a combination of forces that act simultaneously, but the mechanisms underpinning their relative influences remain elusive. This gap strongly limits our ability to predict human impacts on microbial communities and the processes they regulate. Here, we experimentally demonstrate that increased salinity stress, food web alteration and nutrient loading interact to drive outcomes in salt marsh fungal leaf communities. Both salinity stress and food web alterations drove communities to deterministically diverge, resulting in distinct fungal communities. Increased nutrient loads, nevertheless, partially suppressed the influence of other factors as determinants of fungal assembly. Using a nullmore » model approach, we found that increased nutrient loads enhanced the relative importance of stochastic over deterministic divergent processes; without increased nutrient loads, samples from different treatments showed a relatively (deterministic) divergent community assembly whereas increased nutrient loads drove the system to more stochastic assemblies, suppressing the effect of other treatments. These results demonstrate that common anthropogenic modifications can interact to control fungal community assembly. As a result, our results suggest that when the environmental conditions are spatially heterogeneous (as in our case, caused by specific combinations of experimental treatments), increased stochasticity caused by greater nutrient inputs can reduce the importance of deterministic filters that otherwise caused divergence, thus driving to microbial community homogenization.« less

  6. Responds of Bone Cells to Microgravity: Ground-Based Research

    NASA Astrophysics Data System (ADS)

    Zhang, Jian; Li, Jingbao; Xu, Huiyun; Yang, Pengfei; Xie, Li; Qian, Airong; Zhao, Yong; Shang, Peng

    2015-11-01

    Severe loss of bone occurs due to long-duration spaceflight. Mechanical loading stimulates bone formation, while bone degradation happens under mechanical unloading. Bone remodeling is a dynamic process in which bone formation and bone resorption are tightly coupled. Increased bone resorption and decreased bone formation caused by reduced mechanical loading, generally result in disrupted bone remodeling. Bone remodeling is orchestrated by multiple bone cells including osteoblast, osteocyte, osteoclast and mesenchymal stem cell. It is yet not clear that how these bone cells sense altered gravity, translate physical stimulus into biochemical signals, and then regulate themselves structurally and functionally. In this paper, studies elucidating the bioeffects of microgravity on bone cells (osteoblast, osteocyte, osteoclast, mesenchymal stem cell) using various platforms including spaceflight and ground-based simulated microgravity were summarized. Promising gravity-sensitive signaling pathways and protein molecules were proposed.

  7. Joint power and kinematics coordination in load carriage running: Implications for performance and injury.

    PubMed

    Liew, Bernard X W; Morris, Susan; Netto, Kevin

    2016-06-01

    Investigating the impact of incremental load magnitude on running joint power and kinematics is important for understanding the energy cost burden and potential injury-causative mechanisms associated with load carriage. It was hypothesized that incremental load magnitude would result in phase-specific, joint power and kinematic changes within the stance phase of running, and that these relationships would vary at different running velocities. Thirty-one participants performed running while carrying three load magnitudes (0%, 10%, 20% body weight), at three velocities (3, 4, 5m/s). Lower limb trajectories and ground reaction forces were captured, and global optimization was used to derive the variables. The relationships between load magnitude and joint power and angle vectors, at each running velocity, were analyzed using Statistical Parametric Mapping Canonical Correlation Analysis. Incremental load magnitude was positively correlated to joint power in the second half of stance. Increasing load magnitude was also positively correlated with alterations in three dimensional ankle angles during mid-stance (4.0 and 5.0m/s), knee angles at mid-stance (at 5.0m/s), and hip angles during toe-off (at all velocities). Post hoc analyses indicated that at faster running velocities (4.0 and 5.0m/s), increasing load magnitude appeared to alter power contribution in a distal-to-proximal (ankle→hip) joint sequence from mid-stance to toe-off. In addition, kinematic changes due to increasing load influenced both sagittal and non-sagittal plane lower limb joint angles. This study provides a list of plausible factors that may influence running energy cost and injury risk during load carriage running. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Fruit load induces changes in global gene expression and in abscisic acid (ABA) and indole acetic acid (IAA) homeostasis in citrus buds.

    PubMed

    Shalom, Liron; Samuels, Sivan; Zur, Naftali; Shlizerman, Lyudmila; Doron-Faigenboim, Adi; Blumwald, Eduardo; Sadka, Avi

    2014-07-01

    Many fruit trees undergo cycles of heavy fruit load (ON-Crop) in one year, followed by low fruit load (OFF-Crop) the following year, a phenomenon known as alternate bearing (AB). The mechanism by which fruit load affects flowering induction during the following year (return bloom) is still unclear. Although not proven, it is commonly accepted that the fruit or an organ which senses fruit presence generates an inhibitory signal that moves into the bud and inhibits apical meristem transition. Indeed, fruit removal from ON-Crop trees (de-fruiting) induces return bloom. Identification of regulatory or metabolic processes modified in the bud in association with altered fruit load might shed light on the nature of the AB signalling process. The bud transcriptome of de-fruited citrus trees was compared with those of ON- and OFF-Crop trees. Fruit removal resulted in relatively rapid changes in global gene expression, including induction of photosynthetic genes and proteins. Altered regulatory mechanisms included abscisic acid (ABA) metabolism and auxin polar transport. Genes of ABA biosynthesis were induced; however, hormone analyses showed that the ABA level was reduced in OFF-Crop buds and in buds shortly following fruit removal. Additionally, genes associated with Ca(2+)-dependent auxin polar transport were remarkably induced in buds of OFF-Crop and de-fruited trees. Hormone analyses showed that auxin levels were reduced in these buds as compared with ON-Crop buds. In view of the auxin transport autoinhibition theory, the possibility that auxin distribution plays a role in determining bud fate is discussed. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  9. The role of fracture mechanics in the design of fuel tanks in space vehicles

    NASA Technical Reports Server (NTRS)

    Denton, S. J.; Liu, C. K.

    1976-01-01

    With special reference to design of fuel tanks in space vehicles, the principles of fracture mechanics are reviewed. An approximate but extremely simple relationship is derived among the operating stress level, the length of crack, and the number of cycles of failure. Any one of the variables can be computed approximately from the knowledge of the other two, if the loading schedule (mission of the tank) is not greatly altered. Two sample examples illustrating the procedures of determining the allowable safe operating stress corresponding to a set of assumed loading schedule are included. The selection of sample examples is limited by the relatively meager available data on the candidate material for various stress ratios in the cycling.

  10. The Interface of Mechanics and Nociception in Joint Pathophysiology: Insights From the Facet and Temporomandibular Joints

    PubMed Central

    Sperry, Megan M.; Ita, Meagan E.; Kartha, Sonia; Zhang, Sijia; Yu, Ya-Hsin; Winkelstein, Beth

    2017-01-01

    Chronic joint pain is a widespread problem that frequently occurs with aging and trauma. Pain occurs most often in synovial joints, the body's load bearing joints. The mechanical and molecular mechanisms contributing to synovial joint pain are reviewed using two examples, the cervical spinal facet joints and the temporomandibular joint (TMJ). Although much work has focused on the macroscale mechanics of joints in health and disease, the combined influence of tissue mechanics, molecular processes, and nociception in joint pain has only recently become a focus. Trauma and repeated loading can induce structural and biochemical changes in joints, altering their microenvironment and modifying the biomechanics of their constitutive tissues, which themselves are innervated. Peripheral pain sensors can become activated in response to changes in the joint microenvironment and relay pain signals to the spinal cord and brain where pain is processed and perceived. In some cases, pain circuitry is permanently changed, which may be a potential mechanism for sustained joint pain. However, it is most likely that alterations in both the joint microenvironment and the central nervous system (CNS) contribute to chronic pain. As such, the challenge of treating joint pain and degeneration is temporally and spatially complicated. This review summarizes anatomy, physiology, and pathophysiology of these joints and the sensory pain relays. Pain pathways are postulated to be sensitized by many factors, including degeneration and biochemical priming, with effects on thresholds for mechanical injury and/or dysfunction. Initiators of joint pain are discussed in the context of clinical challenges including the diagnosis and treatment of pain. PMID:28056123

  11. Mechanical alterations during interval-training treadmill runs in high-level male team-sport players.

    PubMed

    Girard, Olivier; Brocherie, Franck; Morin, Jean-Benoit; Millet, Grégoire P

    2017-01-01

    To examine mechanical alterations during interval-training treadmill runs in high-level team-sport players. Within-participants repeated measures. Twenty high-level male field-hockey players performed six 30-s runs at 5.53±0.19ms -1 corresponding to 115% of their velocity associated with maximal oxygen uptake (vVO 2max ) with 30-s passive recovery on an instrumented treadmill. Continuous measurement of running kinetics/kinematics and spring-mass characteristics were performed and values were subsequently averaged over 20s (8th-28ths) for comparison. Contact time (+1.1±4.3%; p=0.044), aerial time (+4.1±5.3%; p=0.001), step length (+2.4±2.2%; p<0.001) along with mean loading rates (+7.1±10.6%; p=0.026) increased from the first to the last interval, whereas step frequency (-2.3±2.1%; p<0.001) decreased. Both centre of mass vertical displacement (+3.0±6.0%; p<0.001) and leg compression (+2.8±9.7%; p=0.036), but not peak vertical forces (0.0±4.1%; p=0.761), increased with fatigue. Vertical stiffness decreased (-2.8±6.9%; p=0.012), whereas leg stiffness did not change across intervals (p=0.149). During interval-training treadmill runs, high-level team-sport players modified their mechanical behaviour towards lower vertical stiffness while preserving a constant leg stiffness. Maintenance of running velocity induced longer step lengths and decreased step frequencies that were also accompanied by increased impact loading rates. These mechanical alterations occurred early during the set. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  12. Feasibility Study of a Wearable Exoskeleton for Children: Is the Gait Altered by Adding Masses on Lower Limbs?

    PubMed Central

    Rossi, Stefano; Colazza, Alessandra; Petrarca, Maurizio; Castelli, Enrico; Cappa, Paolo; Krebs, Hermano Igo

    2013-01-01

    We are designing a pediatric exoskeletal ankle robot (pediatric Anklebot) to promote gait habilitation in children with Cerebral Palsy (CP). Few studies have evaluated how much or whether the unilateral loading of a wearable exoskeleton may have the unwanted effect of altering significantly the gait. The purpose of this study was to evaluate whether adding masses up to 2.5 kg, the estimated overall added mass of the mentioned device, at the knee level alters the gait kinematics. Ten healthy children and eight children with CP, with light or mild gait impairment, walked wearing a knee brace with several masses. Gait parameters and lower-limb joint kinematics were analyzed with an optoelectronic system under six conditions: without brace (natural gait) and with masses placed at the knee level (0.5, 1.0, 1.5, 2.0, 2.5 kg). T-tests and repeated measures ANOVA tests were conducted in order to find noteworthy differences among the trial conditions and between loaded and unloaded legs. No statistically significant differences in gait parameters for both healthy children and children with CP were observed in the five “with added mass” conditions. We found significant differences among “natural gait” and “with added masses” conditions in knee flexion and hip extension angles for healthy children and in knee flexion angle for children with CP. This result can be interpreted as an effect of the mechanical constraint induced by the knee brace rather than the effect associated with load increase. The study demonstrates that the mechanical constraint induced by the brace has a measurable effect on the gait of healthy children and children with CP and that the added mass up to 2.5 kg does not alter the lower limb kinematics. This suggests that wearable devices weighing 25 N or less will not noticeably modify the gait patterns of the population examined here. PMID:24023822

  13. Feasibility study of a wearable exoskeleton for children: is the gait altered by adding masses on lower limbs?

    PubMed

    Rossi, Stefano; Colazza, Alessandra; Petrarca, Maurizio; Castelli, Enrico; Cappa, Paolo; Krebs, Hermano Igo

    2013-01-01

    We are designing a pediatric exoskeletal ankle robot (pediatric Anklebot) to promote gait habilitation in children with Cerebral Palsy (CP). Few studies have evaluated how much or whether the unilateral loading of a wearable exoskeleton may have the unwanted effect of altering significantly the gait. The purpose of this study was to evaluate whether adding masses up to 2.5 kg, the estimated overall added mass of the mentioned device, at the knee level alters the gait kinematics. Ten healthy children and eight children with CP, with light or mild gait impairment, walked wearing a knee brace with several masses. Gait parameters and lower-limb joint kinematics were analyzed with an optoelectronic system under six conditions: without brace (natural gait) and with masses placed at the knee level (0.5, 1.0, 1.5, 2.0, 2.5 kg). T-tests and repeated measures ANOVA tests were conducted in order to find noteworthy differences among the trial conditions and between loaded and unloaded legs. No statistically significant differences in gait parameters for both healthy children and children with CP were observed in the five "with added mass" conditions. We found significant differences among "natural gait" and "with added masses" conditions in knee flexion and hip extension angles for healthy children and in knee flexion angle for children with CP. This result can be interpreted as an effect of the mechanical constraint induced by the knee brace rather than the effect associated with load increase. The study demonstrates that the mechanical constraint induced by the brace has a measurable effect on the gait of healthy children and children with CP and that the added mass up to 2.5 kg does not alter the lower limb kinematics. This suggests that wearable devices weighing 25 N or less will not noticeably modify the gait patterns of the population examined here.

  14. Load transfer in the proximal tibia following implantation with a unicompartmental knee replacement: a static snapshot.

    PubMed

    Simpson, D J; Kendrick, B J L; Dodd, C A F; Price, A J; Gill, H S; Murray, D W

    2011-05-01

    Unicompartmental knee replacement (UKR) is an appealing alternative to total knee replacement when the patient has isolated medial compartment osteoarthritis. A common observation post-operatively is radiolucency between the tibial tray wall and the bone. In addition, some patients complain of persistent pain over the proximal tibia antero-medially; this may be related to elevated bone strains in the tibia. Currently, there is no intentionally made mechanical bond between the vertical wall of an Oxford UKR and the adjacent bone; whether one exists or not will influence the load transmission in the proximal tibia and may affect the elevated tibia strain. The aim of this study was to investigate how introducing a mechanical tie between the tibial tray wall and the adjacent bone might alter the load carried into the tibia for both cemented and cementless UKRs. Strain energy density in the region of bone adjacent to the tray wall was considerably increased when a mechanical tie was introduced; this has the potential of reducing the likelihood of a radiolucency occurring in that region. Moreover, a mechanical tie had the effect of reducing proximal tibia strain, which may decrease the incidence of pain following implantation with a UKR.

  15. [Formation Mechanism of Aerobic Granular Sludge and Removal Efficiencies in Integrated ABR-CSTR Reactor].

    PubMed

    Wu, Kai-cheng; Wu, Peng; Xu, Yue-zhong; Li, Yue-han; Shen, Yao-liang

    2015-08-01

    Anaerobic Baffled Reactor (ABR) was altered to make an integrated anaerobic-aerobic reactor. The research investigated the mechanism of aerobic sludge granulation, under the condition of continuous-flow. The last two compartments of the ABR were altered into aeration tank and sedimentation tank respectively with seeded sludge of anaerobic granular sludge in anaerobic zone and conventional activated sludge in aerobic zone. The HRT was gradually decreased in sedimentation tank from 2.0 h to 0.75 h and organic loading rate was increased from 1.5 kg x (M3 x d)(-1) to 2.0 kg x (M3 x d)(-1) while the C/N of 2 was controlled in aerobic zone. When the system operated for 110 days, the mature granular sludge in aerobic zone were characterized by compact structure, excellent sedimentation performance (average sedimentation rate was 20.8 m x h(-1)) and slight yellow color. The system performed well in nitrogen and phosphorus removal under the conditions of setting time of 0.75 h and organic loading rate of 2.0 kg (m3 x d)(-1) in aerobic zone, the removal efficiencies of COD, NH4+ -N, TP and TN were 90%, 80%, 65% and 45%, respectively. The results showed that the increasing selection pressure and the high organic loading rate were the main propulsions of the aerobic sludge granulation.

  16. Understanding behavioral effects of early life stress using the reactive scope and allostatic load models

    PubMed Central

    HOWELL, BRITTANY R.; SANCHEZ, MAR M.

    2015-01-01

    The mechanisms through which early life stress leads to psychopathology are thought to involve allostatic load, the “wear and tear” an organism is subjected to as a consequence of sustained elevated levels of glucocorticoids caused by repeated/prolonged stress activations. The allostatic load model described this phenomenon, but has been criticized as inadequate to explain alterations associated with early adverse experience in some systems, including behavior, which cannot be entirely explained from an energy balance perspective. The reactive scope model has been more recently proposed and focuses less on energy balance and more on dynamic ranges of physiological and behavioral mediators. In this review we examine the mechanisms underlying the behavioral consequences of early life stress in the context of both these models. We focus on adverse experiences that involve mother–infant relationship disruption, and dissect those mechanisms involving maternal care as a regulator of development of neural circuits that control emotional and social behaviors in the offspring. We also discuss the evolutionary purpose of the plasticity in behavioral development, which has a clear adaptive value in a changing environment. PMID:22018078

  17. Analysis of role of bone compliance on mechanics of a lumbar motion segment.

    PubMed

    Shirazi-Adl, A

    1994-11-01

    A large deformation elasto-static finite element formulation is developed and used for the determination of the role of bone compliance in mechanics of a lumbar motion segment. This is done by simulating each vertebra as a deformable body with realistic material properties, as a deformable body with stiffer or softer mechanical properties, as a single rigid body, or finally as two rigid bodies attached by deformable beams. The single loadings of axial compression, flexion moment, extension moment, and axial torque are considered. The results indicate the marked effect of alteration in bone material properties on biomechanics of lumbar segments specially under larger loads. The biomechanical studies of the lumbar spine should, therefore, be performed and evaluated in the light of such dependency. A model for bony vertebrae is finally proposed that preserves both the accuracy and the cost-efficiency in nonlinear finite element analyses of spinal multi-motion segment systems.

  18. The role of embryo movement in the development of the furcula.

    PubMed

    Pollard, A S; Boyd, S; McGonnell, I M; Pitsillides, A A

    2017-03-01

    The pectoral girdle is a complex structure which varies in its morphology between species. A major component in birds is the furcula, which can be considered equivalent to a fusion of the paired clavicles found in many mammals, and the single interclavicle found in many reptiles. These elements are a remnant of the dermal skeleton and the only intramembranous bones in the trunk. Postnatally, the furcula plays important mechanical roles by stabilising the shoulder joint and acting as a mechanical spring during flight. In line with its mechanical role, previous studies indicate that, unlike many other intramembranous bones, furcula growth during development can be influenced by mechanical stimuli. This study investigated the response of individual aspects of furcula growth to both embryo immobilisation and hypermotility in the embryonic chicken. The impact of altered incubation temperature, which influences embryo motility, on crocodilian interclavicle development was also explored. We employed whole-mount bone and cartilage staining and 3D imaging by microCT to quantify the impact of rigid paralysis, flaccid paralysis and hypermobility on furcula growth in the chicken, and 3D microCT imaging to quantify the impact of reduced temperature (32-28 °C) and motility on interclavicle growth in the crocodile. This revealed that the growth rates of the clavicular and interclavicular components of the furcula differ during normal development. Total furcula area was reduced by total unloading produced by flaccid paralysis, but not by rigid paralysis which maintains static loading of embryonic bones. This suggests that dynamic loading, which is required for postnatal bone adaptation, is not a requirement for prenatal furcula growth. Embryo hypermotility also had no impact on furcula area or arm length. Furcula 3D shape did, however, differ between groups; this was marked in the interclavicular component of the furcula, the hypocleideum. Hypocleideum length was reduced by both methods of immobilisation, and interclavicle area was reduced in crocodile embryos incubated at 28 °C, which are less motile than embryos incubated at 32 °C. These data suggest that the clavicular and interclavicle components of the avian furcula respond differently to alterations in embryo movement, with the interclavicle requiring both the static and dynamic components of movement-related loading for normal growth, while static loading preserved most aspects of clavicle growth. Our data suggest that embryo movement, and the mechanical loading this produces, is important in shaping these structures during development to suit their postnatal mechanical roles. © 2016 Anatomical Society.

  19. Activation of Wnt Signaling by Mechanical Loading Is Impaired in the Bone of Old Mice

    PubMed Central

    Holguin, Nilsson; Brodt, Michael D; Silva, Matthew J

    2017-01-01

    Aging diminishes bone formation engendered by mechanical loads, but the mechanism for this impairment remains unclear. Because Wnt signaling is required for optimal loading-induced bone formation, we hypothesized that aging impairs the load-induced activation of Wnt signaling. We analyzed dynamic histomorphometry of 5-month-old, 12-month-old, and 22-month-old C57Bl/6JN mice subjected to multiple days of tibial compression and corroborated an age-related decline in the periosteal loading response on day 5. Similarly, 1 day of loading increased periosteal and endocortical bone formation in young-adult (5-month-old) mice, but old (22-month-old) mice were unresponsive. These findings corroborated mRNA expression of genes related to bone formation and the Wnt pathway in tibias after loading. Multiple bouts (3 to 5 days) of loading upregulated bone formation–related genes, e.g., Osx and Col1a1, but older mice were significantly less responsive. Expression of Wnt negative regulators, Sost and Dkk1, was suppressed with a single day of loading in all mice, but suppression was sustained only in young-adult mice. Moreover, multiple days of loading repeatedly suppressed Sost and Dkk1 in young-adult, but not in old tibias. The age-dependent response to loading was further assessed by osteocyte staining for Sclerostin and LacZ in tibia of TOPGAL mice. After 1 day of loading, fewer osteocytes were Sclerostin-positive and, corroboratively, more osteocytes were LacZ-positive (Wnt active) in both 5-month-old and 12-month-old mice. However, although these changes were sustained after multiple days of loading in 5-month-old mice, they were not sustained in 12-month-old mice. Last, Wnt1 and Wnt7b were the most load-responsive of the 19 Wnt ligands. However, 4 hours after a single bout of loading, although their expression was upregulated threefold to 10-fold in young-adult mice, it was not altered in old mice. In conclusion, the reduced bone formation response of aged mice to loading may be due to failure to sustain Wnt activity with repeated loading. PMID:27357062

  20. Effects of inter-individual lumbar spine geometry variation on load-sharing: Geometrically personalized Finite Element study.

    PubMed

    Naserkhaki, Sadegh; Jaremko, Jacob L; El-Rich, Marwan

    2016-09-06

    There is a large, at times contradictory, body of research relating spinal curvature to Low Back Pain (LBP). Mechanical load is considered as important factor in LBP etiology. Geometry of the spinal structures and sagittal curvature of the lumbar spine govern its mechanical behavior. Thus, understanding how inter-individual geometry particularly sagittal curvature variation affects the spinal load-sharing becomes of high importance in LBP assessment. This study calculated and compared kinematics and load-sharing in three ligamentous lumbosacral spines: one hypo-lordotic (Hypo-L) with low lordosis, one normal-lordotic (Norm-L) with normal lordosis, and one hyper-lordotic (Hyper-L) with high lordosis in flexed and extended postures using 3D nonlinear Finite Element (FE) modeling. These postures were simulated by applying Follower Load (FL) combined with flexion or extension moment. The Hypo-L spine demonstrated stiffer behavior in flexion but more flexible response to extension compared to the Norm-L spine. The excessive lordosis stiffened response of the Hyper-L spine to extension but did not affect its resistance to flexion compared to the Norm-L spine. Despite the different resisting actions of the posterior ligaments to flexion moment, the increase of disc compression was similar in all the spines leading to similar load-sharing. However, resistance of the facet joints to extension was more important in the Norm- and Hyper-L spines which reduced the disc compression. The spinal curvature strongly influenced the magnitude and location of load on the spinal components and also altered the kinematics and load-sharing particularly in extension. Consideration of the subject-specific geometry and sagittal curvature should be an integral part of mechanical analysis of the lumbar spine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Using "Mighty Mouse" to understand masticatory plasticity: myostatin-deficient mice and musculoskeletal function.

    PubMed

    Ravosa, Matthew J; López, Elisabeth K; Menegaz, Rachel A; Stock, Stuart R; Stack, M Sharon; Hamrick, Mark W

    2008-09-01

    Knockout mice lacking myostatin (Mstn), a negative regulator of the growth of skeletal muscle, develop significant increases in the relative mass of masticatory muscles as well as the ability to generate higher maximal muscle forces. Wild-type and Mstn-deficient mice were compared to investigate the postnatal influence of elevated masticatory loads due to increased jaw-adductor and bite forces on the biomineralization of mandibular articular and cortical bone, the internal structure of the jaw joints, and the composition of temporomandibular joint (TMJ) articular cartilage. To provide an interspecific perspective on the long-term responses of mammalian jaw joints to altered loading conditions, the findings on mice were compared to similar data for growing rabbits subjected to long-term dietary manipulation. Statistically significant differences in joint proportions and bone mineral density between normal and Mstn-deficient mice, which are similar to those observed between rabbit loading cohorts, underscore the need for a comprehensive analysis of masticatory tissue plasticity vis-à-vis altered mechanical loads, one in which variation in external and internal structure are considered. Differences in the expression of proteoglycans and type-II collagen in TMJ articular cartilage between the mouse and rabbit comparisons suggest that the duration and magnitude of the loading stimulus will significantly affect patterns of adaptive and degradative responses. These data on mammals subjected to long-term loading conditions offer novel insights regarding variation in ontogeny, life history, and the ecomorphology of the feeding apparatus.

  2. Effect of cranial cruciate ligament deficiency, tibial plateau leveling osteotomy, and tibial tuberosity advancement on contact mechanics and alignment of the stifle in flexion.

    PubMed

    Kim, Stanley E; Pozzi, Antonio; Banks, Scott A; Conrad, Bryan P; Lewis, Daniel D

    2010-04-01

    To assess contact mechanics and 3-dimensional (3-D) joint alignment in cranial cruciate ligament (CCL)-deficient stifles before and after tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA) with the stifle in 90 degrees of flexion. In vitro biomechanical study. Cadaveric pelvic limb pairs (n=8) from dogs weighing 28-35 kg. Contralateral limbs were assigned to receive TPLO or TTA. Digital pressure sensors were used to measure femorotibial contact area, peak and mean contact pressure, and peak pressure location with the limb under a load of 30% body weight and stifle flexion angle of 90 degrees . 3-D poses were obtained using a Microscribe digitizer. Specimens were tested under normal, CCL deficient, and treatment conditions. Significant disturbances in alignment were not observed after CCL transection, although medial contact area was 10% smaller than normal (P=.003). There were no significant differences in contact mechanics or alignment between normal and TTA conditions; TPLO induced 6 degrees varus angulation (P<.001), 26% decrease in lateral peak pressure (P=.027), and 18% increase in medial mean pressure (P=.008) when compared with normal. Cranial tibial subluxation is nominal in CCL-deficient stifles loaded in flexion. Stifle alignment and contact mechanics are not altered by TTA, whereas TPLO causes mild varus and a subsequent increase in medial compartment loading. Cranial tibial subluxation of CCL-deficient stifles may not occur during postures that load the stifle in flexion. The significance of minor changes in loading patterns after TPLO is unknown.

  3. Skeletal Adaptation to Intramedullary Pressure-Induced Interstitial Fluid Flow Is Enhanced in Mice Subjected to Targeted Osteocyte Ablation

    PubMed Central

    Kwon, Ronald Y.; Meays, Diana R.; Meilan, Alexander S.; Jones, Jeremiah; Miramontes, Rosa; Kardos, Natalie; Yeh, Jiunn-Chern; Frangos, John A.

    2012-01-01

    Interstitial fluid flow (IFF) is a potent regulatory signal in bone. During mechanical loading, IFF is generated through two distinct mechanisms that result in spatially distinct flow profiles: poroelastic interactions within the lacunar-canalicular system, and intramedullary pressurization. While the former generates IFF primarily within the lacunar-canalicular network, the latter generates significant flow at the endosteal surface as well as within the tissue. This gives rise to the intriguing possibility that loading-induced IFF may differentially activate osteocytes or surface-residing cells depending on the generating mechanism, and that sensation of IFF generated via intramedullary pressurization may be mediated by a non-osteocytic bone cell population. To begin to explore this possibility, we used the Dmp1-HBEGF inducible osteocyte ablation mouse model and a microfluidic system for modulating intramedullary pressure (ImP) to assess whether structural adaptation to ImP-driven IFF is altered by partial osteocyte depletion. Canalicular convective velocities during pressurization were estimated through the use of fluorescence recovery after photobleaching and computational modeling. Following osteocyte ablation, transgenic mice exhibited severe losses in bone structure and altered responses to hindlimb suspension in a compartment-specific manner. In pressure-loaded limbs, transgenic mice displayed similar or significantly enhanced structural adaptation to Imp-driven IFF, particularly in the trabecular compartment, despite up to ∼50% of trabecular lacunae being uninhabited following ablation. Interestingly, regression analysis revealed relative gains in bone structure in pressure-loaded limbs were correlated with reductions in bone structure in unpressurized control limbs, suggesting that adaptation to ImP-driven IFF was potentiated by increases in osteoclastic activity and/or reductions in osteoblastic activity incurred independently of pressure loading. Collectively, these studies indicate that structural adaptation to ImP-driven IFF can proceed unimpeded following a significant depletion in osteocytes, consistent with the potential existence of a non-osteocytic bone cell population that senses ImP-driven IFF independently and potentially parallel to osteocytic sensation of poroelasticity-derived IFF. PMID:22413015

  4. Sponge-Like Dressings Based on the Association of Chitosan and Sericin for the Treatment of Chronic Skin Ulcers. II. Loading of the Hemoderivative Platelet Lysate.

    PubMed

    Mori, Michela; Rossi, Silvia; Ferrari, Franca; Bonferoni, Maria C; Sandri, Giuseppina; Riva, Federica; Tenci, Marika; Del Fante, Claudia; Nicoletti, Giovanni; Caramella, Carla

    2016-03-01

    Platelet lysate (PL) was loaded into dressings based on chitosan glutamate (CSG) low and high molecular weight, sericin (Ser), and glycine (Gly). A synergic effect of Ser and PL on fibroblast proliferation was proved in vitro. Two different PL loading approaches were considered: the first provided to prepare dressings by freeze-drying a mixture of PL and CSG/Gly/Ser solution, the second approach consisted in the extemporarily loading of PL in the CSG/Gly/Ser freeze-dried dressings. As for the first approach, PL loading did not produce any variation in dressing mechanical properties. Such dressings absorbed a high amount (about 8-fold of dry weight) of phosphate-buffered saline (fluid mimicking wound exudate), forming a gel with pseudoplastic and elastic properties. Platelet-derived growth factor AB assay indicated that neither freeze-drying nor the excipients alter PL growth factor content. As for the second approach, mechanical and rheological properties of the gel formed upon PL absorption enabled to choose a PL loading of about 90 μL/cm(2). Upon contact with fibroblasts, all PL loaded formulations increased the number not only of viable cells but also of those in the proliferative phase. Histological studies effected on human skin strips pointed out the positive effect of PL loaded dressings on dermal matrix reconstruction. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Effects of chemical alteration on fracture mechanical properties in hydrothermal systems

    NASA Astrophysics Data System (ADS)

    Callahan, O. A.; Eichhubl, P.; Olson, J. E.

    2015-12-01

    Fault and fracture networks often control the distribution of fluids and heat in hydrothermal and epithermal systems, and in related geothermal and mineral resources. Additional chemical influences on conduit evolution are well documented, with dissolution and precipitation of mineral species potentially changing the permeability of fault-facture networks. Less well understood are the impacts of chemical alteration on the mechanical properties governing fracture growth and fracture network geometry. We use double-torsion (DT) load relaxation tests under ambient air conditions to measure the mode-I fracture toughness (KIC) and subcritical fracture growth index (SCI) of variably altered rock samples obtained from outcrop in Dixie Valley, NV. Samples from southern Dixie Valley include 1) weakly altered granite, characterized by minor sericite in plagioclase, albitization and vacuolization of feldspars, and incomplete replacement of biotite with chlorite, and 2) granite from an area of locally intense propylitic alteration with chlorite-calcite-hematite-epidote assemblages. We also evaluated samples of completely silicified gabbro obtained from the Dixie Comstock epithermal gold deposit. In the weakly altered granite KIC and SCI are 1.3 ±0.2 MPam1/2 (n=8) and 59 ±25 (n=29), respectively. In the propylitic assemblage KIC is reduced to 0.6 ±0.1 MPam1/2 (n=11), and the SCI increased to 75 ±36 (n = 33). In both cases, the altered materials have lower fracture toughness and higher SCI than is reported for common geomechanical standards such as Westerly Granite (KIC ~1.7 MPam1/2; SCI ~48). Preliminary analysis of the silicified gabbro shows a significant increase in fracture toughness, 3.6 ±0.4 MPam1/2 (n=2), and SCI, 102 ±45 (n=19), compared to published values for gabbro (2.9 MPam1/2 and SCI = 32). These results suggest that mineralogical and textural changes associated with different alteration assemblages may result in spatially variable rates of fracture initiation and growth in different parts of hydrothermal systems. Contrasting fracture mechanical properties between alteration assemblages may constitute a new mechanism of chemical-mechanical feedback that contributes to the localization of conduits in hydrothermal systems.

  6. In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae

    PubMed Central

    Ko, Frank C.; Dragomir, Cecilia; Plumb, Darren A.; Goldring, Steven R.; Wright, Timothy M.; Goldring, Mary B.; van der Meulen, Marjolein C.H.

    2013-01-01

    Objectives Alterations in the mechanical loading environment in joints may have both beneficial and detrimental effects on articular cartilage and subchondral bone and subsequently influence the development of osteoarthritis (OA). We used an in vivo tibial loading model to investigate the adaptive responses of cartilage and bone to mechanical loading and to assess the influence of load level and duration. Methods We applied cyclic compression of 4.5 and 9.0N peak loads to the left tibia via the knee joint of adult (26-week-old) C57Bl/6 male mice for 1, 2, and 6 weeks. Only 9.0N loading was utilized in young (10-week-old) mice. The changes in articular cartilage and subchondral bone were analyzed by histology and microcomputed tomography. Results Loading promoted cartilage damage in both age groups, with increased damage severity dependent upon the duration of loading. Metaphyseal bone mass increased in the young mice, but not in the adult mice, whereas epiphyseal cancellous bone mass decreased with loading in both young and adult mice. Articular cartilage thickness decreased, and subchondral cortical bone thickness increased in the posterior tibial plateau in both age groups. Both age groups developed periarticular osteophytes at the tibial plateau in response to the 9.0N load, but no osteophyte formation occurred in adult mice subjected to 4.5N peak loading. Conclusion This non-invasive loading model permits dissection of temporal and topographical changes in cartilage and bone and will enable investigation of the efficacy of treatment interventions targeting joint biomechanics or biological events that promote OA onset and progression. PMID:23436303

  7. Patterning of alloy precipitation through external pressure

    NASA Astrophysics Data System (ADS)

    Franklin, Jack A.

    Due to the nature of their microstructure, alloyed components have the benefit of meeting specific design goals across a wide range of electrical, thermal, and mechanical properties. In general by selecting the correct alloy system and applying a proper heat treatment it is possible to create a metallic sample whose properties achieve a unique set of design requirements. This dissertation presents an innovative processing technique intended to control both the location of formation and the growth rates of precipitates within metallic alloys in order to create multiple patterned areas of unique microstructure within a single sample. Specific experimental results for the Al-Cu alloy system will be shown. The control over precipitation is achieved by altering the conventional heat treatment process with an external surface load applied to selected locations during the quench and anneal. It is shown that the applied pressures affect both the rate and directionality of the atomic diffusion in regions close to the loaded surfaces. The control over growth rates is achieved by altering the enthalpic energy required for successful diffusion between lattice sites. Changes in the local chemical free energy required to direct the diffusion of atoms are established by introducing a non-uniform elastic strain energy field within the samples created by the patterned surface pressures. Either diffusion rates or atomic mobility can be selected as the dominating control process by varying the quench rate; with slower quenches having greater control over the mobility of the alloying elements. Results have shown control of Al2Cu precipitation over 100 microns on mechanically polished surfaces. Further experimental considerations presented will address consistency across sample ensembles. This includes repeatable pressure loading conditions and the chemical interaction between any furnace environments and both the alloy sample and metallic pressure loading devices.

  8. A new way of thinking about complications of prematurity.

    PubMed

    Moore, Tiffany A; Berger, Ann M; Wilson, Margaret E

    2014-01-01

    The morbidity and mortality of preterm infants are impacted by their ability to maintain physiologic homeostasis using metabolic, endocrine, and immunologic mechanisms independent of the mother's placenta. Exploring McEwen's allostatic load model in preterm infants provides a new way to understand the altered physiologic processes associated with frequently occurring complications of prematurity such as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity. The purpose of this article is to present a new model to enhance understanding of the altered physiologic processes associated with complications of prematurity. The model of allostatic load and complications of prematurity was derived to explore the relationship between general stress of prematurity and complications of prematurity. The proposed model uses the concepts of general stress of prematurity, allostasis, physiologic response patterns (adaptive-maladaptive), allostatic load, and complications of prematurity. These concepts are defined and theoretical relationships in the proposed model are interpreted using the four maladaptive response patterns of repeated hits, lack of adaptation, prolonged response, and inadequate response. Empirical evidence for cortisol, inflammation, and oxidative stress responses are used to support the theoretical relationships. The proposed model provides a new way of thinking about physiologic dysregulation in preterm infants. The ability to describe and understand complex physiologic mechanisms involved in complications of prematurity is essential for research. Advancing the knowledge of complications of prematurity will advance clinical practice and research and lead to testing of interventions to reduce negative outcomes in preterm infants.

  9. Superficial Collagen Fibril Modulus and Pericellular Fixed Charge Density Modulate Chondrocyte Volumetric Behaviour in Early Osteoarthritis

    PubMed Central

    Turunen, Siru M.; Han, Sang Kuy; Herzog, Walter; Korhonen, Rami K.

    2013-01-01

    The aim of this study was to investigate if the experimentally detected altered chondrocyte volumetric behavior in early osteoarthritis can be explained by changes in the extracellular and pericellular matrix properties of cartilage. Based on our own experimental tests and the literature, the structural and mechanical parameters for normal and osteoarthritic cartilage were implemented into a multiscale fibril-reinforced poroelastic swelling model. Model simulations were compared with experimentally observed cell volume changes in mechanically loaded cartilage, obtained from anterior cruciate ligament transected rabbit knees. We found that the cell volume increased by 7% in the osteoarthritic cartilage model following mechanical loading of the tissue. In contrast, the cell volume decreased by 4% in normal cartilage model. These findings were consistent with the experimental results. Increased local transversal tissue strain due to the reduced collagen fibril stiffness accompanied with the reduced fixed charge density of the pericellular matrix could increase the cell volume up to 12%. These findings suggest that the increase in the cell volume in mechanically loaded osteoarthritic cartilage is primarily explained by the reduction in the pericellular fixed charge density, while the superficial collagen fibril stiffness is suggested to contribute secondarily to the cell volume behavior. PMID:23634175

  10. Preserved and impaired aspects of feed-forward grip force control after chronic somatosensory deafferentation.

    PubMed

    Hermsdörfer, J; Elias, Z; Cole, J D; Quaney, B M; Nowak, D A

    2008-01-01

    Although feed-forward mechanisms of grip force control are a prerequisite for skilled object manipulation, somatosensory feedback is essential to acquire, maintain, and adapt these mechanisms. Individuals with complete peripheral deafferentation provide the unique opportunity to study the function of the motor system deprived of somatosensory feedback. Two individuals (GL and IW) with complete chronic deafferentation of the trunk and limbs were tested during cyclic vertical movements of a hand-held object. Such movements induce oscillating loads that are typically anticipated by parallel modulations of the grip force. Load magnitude was altered by varying either the movement frequency or object weight. GL and IW employed excessive grip forces probably reflecting a compensatory mechanism. Despite this overall force increase, both deafferented participants adjusted their grip force level according to the load magnitude, indicating preserved scaling of the background grip force to physical demands. The dynamic modulation of the grip force with the load force was largely absent in GL, whereas in IW only slower movements were clearly affected. The authors hypothesize that the deafferented patients may have utilized visual and vestibular cues and/or an efferent copy of the motor command of the arm movement to scale the grip force level. Severely impaired grip force-load coupling in GL suggests that sensory information is important for maintaining a precise internal model of dynamic grip force control. However, comparably better performance in IW argues for the possibility that alternative cues can be used to trigger a residual internal model.

  11. Time-dependent combinatory effects of active mechanical loading and passive topographical cues on cell orientation.

    PubMed

    Wang, Qian; Huang, Hanyang; Wei, Kang; Zhao, Yi

    2016-10-01

    Mechanical stretching and topographical cues are both effective mechanical stimulations for regulating cell morphology, orientation, and behaviors. The competition of these two mechanical stimulations remains largely underexplored. Previous studies have suggested that a small cyclic mechanical strain is not able to reorient cells that have been pre-aligned by relatively large linear microstructures, but can reorient those pre-aligned by small linear micro/nanostructures if the characteristic dimension of these structures is below a certain threshold. Likewise, for micro/nanostructures with a given characteristic dimension, the strain must exceed a certain magnitude to overrule the topographic cues. There are however no in-depth investigations of such "thresholds" due to the lack of close examination of dynamic cell orientation during and shortly after the mechanical loading. In this study, the time-dependent combinatory effects of active and passive mechanical stimulations on cell orientation are investigated by developing a micromechanical stimulator. The results show that the cells pre-aligned by linear micro/nanostructures can be altered by cyclic in-plane strain, regardless of the structure size. During the loading, the micro/nanostructures can resist the reorientation effects by cyclic in-plane strain while the resistive capability (measured by the mean orientation angle change and the reorientation speed) increases with the increasing characteristic dimension. The micro/nanostructures also can recover the cell orientation after the cessation of cyclic in-plane strain, while the recovering capability increases with the characteristic dimension. The previously observed thresholds are largely dependent on the observation time points. In order to accurately evaluate the combinatory effects of the two mechanical stimulations, observations during the active loading with a short time interval or endpoint observations shortly after the loading are preferred. This study provides a microengineering solution to investigate the time-dependent combinatory effects of the active and passive mechanical stimulations and is expected to enhance our understanding of cell responses to complex mechanical environments. Biotechnol. Bioeng. 2016;113: 2191-2201. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. The Effects of Mechanical Loading on Tendons - An In Vivo and In Vitro Model Study

    PubMed Central

    Zhang, Jianying; Wang, James H-C.

    2013-01-01

    Mechanical loading constantly acts on tendons, and a better understanding of its effects on the tendons is essential to gain more insights into tendon patho-physiology. This study aims to investigate tendon mechanobiological responses through the use of mouse treadmill running as an in vivo model and mechanical stretching of tendon cells as an in vitro model. In the in vivo study, mice underwent moderate treadmill running (MTR) and intensive treadmill running (ITR) regimens. Treadmill running elevated the expression of mechanical growth factors (MGF) and enhanced the proliferative potential of tendon stem cells (TSCs) in both patellar and Achilles tendons. In both tendons, MTR upregulated tenocyte-related genes: collagen type I (Coll. I ∼10 fold) and tenomodulin (∼3–4 fold), but did not affect non-tenocyte-related genes: LPL (adipocyte), Sox9 (chondrocyte), Runx2 and Osterix (both osteocyte). However, ITR upregulated both tenocyte (Coll. I ∼7–11 fold; tenomodulin ∼4–5 fold) and non-tenocyte-related genes (∼3–8 fold). In the in vitro study, TSCs and tenocytes were stretched to 4% and 8% using a custom made mechanical loading system. Low mechanical stretching (4%) of TSCs from both patellar and Achilles tendons increased the expression of only the tenocyte-related genes (Coll. I ∼5–6 fold; tenomodulin ∼6–13 fold), but high mechanical stretching (8%) increased the expression of both tenocyte (Coll. I ∼28–50 fold; tenomodulin ∼14–48 fold) and non-tenocyte-related genes (2–5-fold). However, in tenocytes, non-tenocyte related gene expression was not altered by the application of either low or high mechanical stretching. These findings indicate that appropriate mechanical loading could be beneficial to tendons because of their potential to induce anabolic changes in tendon cells. However, while excessive mechanical loading caused anabolic changes in tendons, it also induced differentiation of TSCs into non-tenocytes, which may lead to the development of degenerative tendinopathy frequently seen in clinical settings. PMID:23977130

  13. NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils.

    PubMed

    Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos

    2016-01-01

    Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance.

  14. Effect of water on nanomechanics of bone is different between tension and compression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Samuel, Jitin; Park, Jun-Sang; Almer, Jonathan

    Water, an important constituent in bone, resides in different compartments in bone matrix and may impose significant effects on its bulk mechanical properties. However, a clear understanding of the mechanistic role of water in toughening bone is yet to emerge. To address this issue, this study used a progressive loading protocol, coupled with measurements of in situ mineral and collagen fibril deformations using synchrotron X-ray diffraction techniques. Using this unique approach, the contribution of water to the ultrastructural behavior of bone was examined by testing bone specimens in different loading modes (tension and compression) and hydration states (wet and dehydrated).more » The results indicated that the effect of water on the mechanical behavior of mineral and collagen phases at the ultrastructural level was loading mode dependent and correlated with the bulk behavior of bone. Tensile loading elicited a transitional drop followed by an increase in load bearing by the mineral phase at the ultrastructural level, which was correlated with a strain hardening behavior of bone at the bulk level. Compression loading caused a continuous loss of load bearing by the mineral phase, which was reflected at the bulk level as a strain softening behavior. In addition, viscous strain relaxation and pre-strain reduction were observed in the mineral phase in the presence of water. Taken together, the results of this study suggest that water dictates the bulk behavior of bone by altering the interaction between mineral crystals and their surrounding matrix.« less

  15. Bone loss during long term space flight is prevented by the application of a short term impulsive mechanical stimulus

    NASA Astrophysics Data System (ADS)

    Goodship, A. E.; Cunningham, J. L.; Oganov, V.; Darling, J.; Miles, A. W.; Owen, G. W.

    In long term space flight, the mechanical forces applied to the skeleton are substantially reduced and are altered in character. This reduced skeletal loading results in a reduction in bone mass. Exercise techmques currently used in space can maintain muscle mass but the mechanical stimulus provided by this exercise does not prevent bone loss. By applying an external impulsive load for a short period each day, which is intended to mimic the heel strike transient, to the lower limb of an astronaut during a long term space flight (5 months), this study tests the hypothesis that the bone cells can be activated by an appropriate external mechanical stimulus to maintain bone mass throughout prolonged periods of weightlessness. A mechanical loading device was developed to produce a loading of the os-calcis similar to that observed during the heel strike transient. The device is activated by the astronaut to provide a transient load to the heel of one leg whilst providing an equivalent exercising load to the other leg. During the EUROMIR95 mission on the MIR space station, an astronaut used this device for a short period daily throughout the duration of the mission. Pre- and post-flight measurements of bone mineral density (BMD) of the os-calcis and femoral neck of the astronaut were made to determine the efficacy of the device in preventing loss of bone mineral during the mission. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which received no stimulus. Post-flight, BMD in both the stimulated and non-stimulated os-calcis reduces, the extent of this reduction however is less in the stimulated os-calcis. For the femoral neck, the mechanical Stimulation does not produce a positive effect. On the os-calcis which received the mechanical stimulus, BMD was maintained throughout the period of the flight, while it was reduced by up to 7% on the os-calcis which received no stimulus. Post-flight, BMD in both the stimulated and non-stimulated os-calcis reduces, the extent of this reduction however is less in the stimulated os-calcis. For the femoral neck, the mechanical stimulation does not produce a positive effect.

  16. Gravity and thermoregulation: metabolic changes and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Robinson, E. L.; Fuller, C. A.

    2000-01-01

    Gravity appears to alter thermoregulation through changes in both the regulated level of body temperature and the rhythmic organization of temperature regulation. Gravity has been hypothesized to have an associated metabolic cost. Increased resting energy expenditure and dietary intake have been observed in animals during centrifuge experiments at hypergravity. Thus far, only animals have shown a corresponding reduction in metabolism in microgravity. Altered heat loss has been proposed as a response to altered gravitational environments, but remains documented only as changes in skin temperature. Changes in circadian timing, including the body temperature rhythm, have been shown in both hypergravity and microgravity, and probably contribute to alterations in sleep and performance. Changes in body temperature regulation may result from circadian disturbance, from the direct or indirect actions of gravity on the regulated temperature, or from changes in thermoregulatory effectors (heat production and heat loss) due to altered gravitational load and convective changes. To date, however, we have little data on the underlying thermoregulatory changes in altered gravity, and thus the precise mechanisms by which gravity alters temperature regulation remain largely unknown.

  17. Are the Kinematics of the Knee Joint Altered during the Loading Response Phase of Gait in Individuals with Concurrent Knee Osteoarthritis and Complaints of Joint Instability? A Dynamic Stereo X-ray Study

    PubMed Central

    Farrokhi, Shawn; Tashman, Scott; Gil, Alexandra B.; Klatt, Brian A.; Fitzgerald, G. Kelley

    2011-01-01

    Background Joint instability has been suggested as a risk factor for knee osteoarthritis and a cause of significant functional declines in those with symptomatic disease. However, the relationship between altered knee joint mechanics and self-reports of instability in individuals with knee osteoarthritis remains unclear. Methods Fourteen subjects with knee osteoarthritis and complaints of joint instability and 12 control volunteers with no history of knee disease were recruited for this study. Dynamic stereo X-ray technology was used to assess the three-dimensional kinematics of the knee joint during the loading response phase of gait. Findings Individuals with concurrent knee osteoarthritis and joint instability demonstrated significantly reduced flexion and internal/external rotation knee motion excursions during the loading response phase of gait (P < 0.01), while the total abduction/adduction range of motion was increased (P < 0.05). In addition, the coronal and transverse plane alignment of the knee joint at initial contact was significantly different (P < 0.05) for individuals with concurrent knee osteoarthritis and joint instability. However, the anteroposterior and mediolateral tibiofemoral joint positions at initial contact and the corresponding total joint translations were similar between groups during the loading phase of gait. Interpretations The rotational patterns of tibiofemoral joint motion and joint alignments reported for individuals with concurrent knee osteoarthritis and joint instability are consistent with those previously established for individuals with knee osteoarthritis. Furthermore, the findings of similar translatory tibiofemoral motion between groups suggest that self-reports of episodic joint instability in individuals with knee osteoarthritis may not necessarily be associated with adaptive alterations in joint arthrokinematics. PMID:22071429

  18. Are the kinematics of the knee joint altered during the loading response phase of gait in individuals with concurrent knee osteoarthritis and complaints of joint instability? A dynamic stereo X-ray study.

    PubMed

    Farrokhi, Shawn; Tashman, Scott; Gil, Alexandra B; Klatt, Brian A; Fitzgerald, G Kelley

    2012-05-01

    Joint instability has been suggested as a risk factor for knee osteoarthritis and a cause of significant functional decline in those with symptomatic disease. However, the relationship between altered knee joint mechanics and self-reports of instability in individuals with knee osteoarthritis remains unclear. Fourteen subjects with knee osteoarthritis and complaints of joint instability and 12 control volunteers with no history of knee disease were recruited for this study. Dynamic stereo X-ray technology was used to assess the three-dimensional kinematics of the knee joint during the loading response phase of gait. Individuals with concurrent knee osteoarthritis and joint instability demonstrated significantly reduced flexion and internal/external rotation knee motion excursions during the loading response phase of gait (P<0.01), while the total abduction/adduction range of motion was increased (P<0.05). In addition, the coronal and transverse plane alignment of the knee joint at initial contact was significantly different (P<0.05) for individuals with concurrent knee osteoarthritis and joint instability. However, the anteroposterior and mediolateral tibiofemoral joint positions at initial contact and the corresponding total joint translations were similar between groups during the loading phase of gait. The rotational patterns of tibiofemoral joint motion and joint alignments reported for individuals with concurrent knee osteoarthritis and joint instability are consistent with those previously established for individuals with knee osteoarthritis. Furthermore, the findings of similar translatory tibiofemoral motion between groups suggest that self-reports of episodic joint instability in individuals with knee osteoarthritis may not necessarily be associated with adaptive alterations in joint arthrokinematics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Thermal/Mechanical Response of a Polymer Matrix Composite at Cryogenic Temperatures

    NASA Technical Reports Server (NTRS)

    Whitley, Karen S.; Gates, Thomas S.

    2003-01-01

    In order for polymeric-matrix composites to be considered for use as structural materials in the next generation of space transportation systems, the mechanical behavior of these materials at cryogenic temperatures must be investigated. This paper presents experimental data on the residual mechanical properties of a carbon-fiber polymeric composite, IM7/PETI-5, both before and after aging. Both tension and compression modulus and strength were measured at room temperature, -196C, and -269 C on five different laminate configurations. One set of specimens was aged isothermally for 576 hours at -184 C in an unconstrained state. Another set of corresponding specimens was aged under constant uniaxial strain for 576 hours at -184 C. Based on the experimental data presented, it is shown that trends in stiffness and strength that result from changes in temperature are not always smooth and consistent. Moreover, it is shown that loading mode and direction are significant for both stiffness and strength, and aging at cryogenic temperature while under load can alter the mechanical properties of pristine, un-aged laminates made of IM7/PETI-5 material.

  20. Measurement of the Mechanical Properties of Intact Collagen Fibrils

    NASA Astrophysics Data System (ADS)

    Mercedes, H.; Heim, A.; Matthews, W. G.; Koob, T.

    2006-03-01

    Motivated by the genetic disorder Ehlers-Danlos syndrome (EDS), in which proper collagen synthesis is interrupted, we are investigating the structural and mechanical properties of collagen fibrils. The fibrous glycoprotein collagen is the most abundant protein found in the human body and plays a key role in the extracellular matrix of the connective tissue, the properties of which are altered in EDS. We have selected as our model system the collagen fibrils of the sea cucumber dermis, a naturally mutable tissue. This system allows us to work with native fibrils which have their proteoglycan complement intact, something that is not possible with reconstituted mammalian collagen fibrils. Using atomic force microscopy, we measure, as a function of the concentration of divalent cations, the fibril diameter, its response to force loading, and the changes in its rigidity. Through these experiments, we will shed light on the mechanisms which control the properties of the sea cucumber dermis and hope to help explain the altered connective tissue extracellular matrix properties associated with EDS.

  1. Effects of morphine on respiratory load detection, load magnitude perception and tactile sensation in obstructive sleep apnea.

    PubMed

    Tomazini Martins, Rodrigo; Carberry, Jayne C; Gandevia, Simon C; Butler, Jane E; Eckert, Danny J

    2018-04-26

    Pharyngeal and respiratory sensation is impaired in obstructive sleep apnea (OSA). Opioids may further diminish respiratory sensation. Thus, protective pharyngeal neuromuscular and arousal responses to airway occlusion that rely on respiratory sensation could be impaired with opioids to worsen OSA severity. However, little is known about the effects of opioids on upper airway and respiratory sensation in people with OSA. This study was designed to determine the effects of 40mg of MS-Contin on tactile sensation, respiratory load detection and respiratory magnitude perception in people with OSA during wakefulness. A double-blind, randomized, cross-over design (1 week wash-out) was used. 21 men with untreated OSA (apnea/hypopnea index=26{plus minus}17events/h) recruited from a larger clinical study completed the protocol. Tactile sensation using von Frey filaments on the back of the hand, internal mucosa of the cheek, uvula and posterior pharyngeal wall were not different between placebo and morphine (e.g. posterior wall=0.16[0.16,0.4]vs. 0.4[0.14,1.8]g, p=0.261). Similarly, compared to placebo, morphine did not alter respiratory load detection thresholds (nadir mask pressure detected=-2.05[-3.37,-1.55] vs. -2.19[-3.36,-1.41]cmH 2 O, p=0.767), or respiratory load magnitude perception (mean Borg scores during a 5 resistive load [range: 5-126cmH 2 O/L/s] protocol=4.5{plus minus}1.6 vs. 4.2{plus minus}1.2, p=0.347) but did reduce minute ventilation during quiet breathing (11.4{plus minus}3.3 vs. 10.7{plus minus}2.6L/min, p<0.01). These findings indicate that 40mg of MS-Contin does not systematically impair tactile or respiratory sensation in men with mild to moderate, untreated, OSA. This suggests that altered respiratory sensation to acute mechanical stimuli is not likely to be a mechanism that contributes to worsening of OSA with a moderate dose of morphine.

  2. Fire treatment effects on vegetation structure, fuels, and potential fire severity in western U.S. forests

    USGS Publications Warehouse

    Stephens, S.L.; Moghaddas, J.J.; Edminster, C.; Fiedler, C.E.; Haase, S.; Harrington, M.; Keeley, J.E.; Knapp, E.E.; Mciver, J.D.; Metlen, K.; Skinner, C.N.; Youngblood, A.

    2009-01-01

    Abstract. Forest structure and species composition in many western U.S. coniferous forests have been altered through fire exclusion, past and ongoing harvesting practices, and livestock grazing over the 20th century. The effects of these activities have been most pronounced in seasonally dry, low and mid-elevation coniferous forests that once experienced frequent, low to moderate intensity, fire regimes. In this paper, we report the effects of Fire and Fire Surrogate (FFS) forest stand treatments on fuel load profiles, potential fire behavior, and fire severity under three weather scenarios from six western U.S. FFS sites. This replicated, multisite experiment provides a framework for drawing broad generalizations about the effectiveness of prescribed fire and mechanical treatments on surface fuel loads, forest structure, and potential fire severity. Mechanical treatments without fire resulted in combined 1-, 10-, and 100-hour surface fuel loads that were significantly greater than controls at three of five FFS sites. Canopy cover was significantly lower than controls at three of five FFS sites with mechanical-only treatments and at all five FFS sites with the mechanical plus burning treatment; fire-only treatments reduced canopy cover at only one site. For the combined treatment of mechanical plus fire, all five FFS sites with this treatment had a substantially lower likelihood of passive crown fire as indicated by the very high torching indices. FFS sites that experienced significant increases in 1-, 10-, and 100-hour combined surface fuel loads utilized harvest systems that left all activity fuels within experimental units. When mechanical treatments were followed by prescribed burning or pile burning, they were the most effective treatment for reducing crown fire potential and predicted tree mortality because of low surface fuel loads and increased vertical and horizontal canopy separation. Results indicate that mechanical plus fire, fire-only, and mechanical-only treatments using whole-tree harvest systems were all effective at reducing potential fire severity under severe fire weather conditions. Retaining the largest trees within stands also increased fire resistance. ?? 2009 by the Ecological Society of America.

  3. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  4. Hindlimb unloading alters ligament healing

    NASA Technical Reports Server (NTRS)

    Provenzano, Paolo P.; Martinez, Daniel A.; Grindeland, Richard E.; Dwyer, Kelley W.; Turner, Joanne; Vailas, Arthur C.; Vanderby, Ray Jr

    2003-01-01

    We investigated the hypothesis that hindlimb unloading inhibits healing in fibrous connective tissue such as ligament. Male rats were assigned to 3- and 7-wk treatment groups with three subgroups each: sham control, ambulatory healing, and hindlimb-suspended healing. Ambulatory and suspended animals underwent surgical rupture of their medial collateral ligaments, whereas sham surgeries were performed on control animals. After 3 or 7 wk, mechanical and/or morphological properties were measured in ligament, muscle, and bone. During mechanical testing, most suspended ligaments failed in the scar region, indicating the greatest impairment was to ligament and not to bone-ligament insertion. Ligament testing revealed significant reductions in maximum force, ultimate stress, elastic modulus, and low-load properties in suspended animals. In addition, femoral mineral density, femoral strength, gastrocnemius mass, and tibialis anterior mass were significantly reduced. Microscopy revealed abnormal scar formation and cell distribution in suspended ligaments with extracellular matrix discontinuities and voids between misaligned, but well-formed, collagen fiber bundles. Hence, stress levels from ambulation appear unnecessary for formation of fiber bundles yet required for collagen to form structurally competent continuous fibers. Results support our hypothesis that hindlimb unloading impairs healing of fibrous connective tissue. In addition, this study provides compelling morphological evidence explaining the altered structure-function relationship in load-deprived healing connective tissue.

  5. Role of the Middle Lumbar Fascia on Spinal Mechanics: A Human Biomechanical Assessment.

    PubMed

    Ranger, Tom A; Newell, Nicolas; Grant, Caroline A; Barker, Priscilla J; Pearcy, Mark J

    2017-04-15

    Biomechanical experiment. The aims of the present study were to test the effect of fascial tension on lumbar segmental axial rotation and lateral flexion and the effect of the angle of fascial attachment. Tension in the middle layer of lumbar fascia has been demonstrated to affect mechanical properties of lumbar segmental flexion and extension in the neutral zone. The effect of tension on segmental axial rotation and lateral flexion has, however, not been investigated. Seven unembalmed lumbar spines were divided into segments and mounted for testing. A 6 degree-of-freedom robotic testing facility was used to displace the segments in each anatomical plane (flexion-extension, lateral bending, and axial rotation) with force and moment data recorded by a load cell positioned beneath the test specimen. Tests were performed with and without a 20 N fascia load and the subsequent forces and moments were compared. In addition, forces and moments were compared when the specimens were held in a set position and the fascia loading angle was varied. A fascial tension of 20 N had no measurable effect on the forces or moments measured when the specimens were displaced in any plane of motion (P > 0.05). When 20 N of fascial load were applied to motion segments in a set position small segmental forces and moments were measured. Changing the angle of the fascial load did not significantly alter these measurements. Application of a 20 N fascial load did not produce a measureable effect on the mechanics of a motion segment, even though it did produce small measurable forces and moments on the segments when in a fixed position. Results from the present study are inconsistent with previous studies, suggesting that further investigation using multiple testing protocols and different loading conditions is required to determine the effects of fascial loading on spinal segment behavior. N/A.

  6. Effect of Dermatan Sulfate on the Indentation and Tensile Properties of Articular Cartilage

    PubMed Central

    Hall, Melanie L.; Krawczak, David A.; Simha, Narendra K.; Lewis, Jack L.

    2009-01-01

    Objective This paper examines the hypothesis that the dermatan sulfate (DS) chain on decorin is a load carrying element in cartilage and that its damage or removal will alter the material properties. Methods To test this hypothesis, indentation and tensile testing of cartilage from bovine patella was performed before and after digestion with chondroitinase B (cB). Removal of significant amounts of DS by cB digestion was verified by Western blot analysis of proteoglycans extracted from whole and sectioned specimens. Specimens (control and treated) were subjected to a series of step-hold displacements. Elastic modulus during the step rise (rapid modulus) and at equilibrium (equilibrium modulus), and the relaxation function during each step were measured for test (cB and buffer) and control (buffer alone) conditions. Results cB had no effect on any of the viscoelastic mechanical properties measured, either in indentation or tension Conclusion Removing or damaging approximately 50% of the dermatan sulfate had no effect on the mechanical properties, strongly suggesting that dermatan sulfate either carries very low load or no load. PMID:19036614

  7. Physical Weight Loading Induces Expression of Tryptophan Hydroxylase 2 in the Brain Stem

    PubMed Central

    Shim, Joon W.; Dodge, Todd R.; Hammond, Max A.; Wallace, Joseph M.; Zhou, Feng C.; Yokota, Hiroki

    2014-01-01

    Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2) that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive) control, and a 90-min tail suspension was used as a stress (negative) control. Expression of tph2 was determined 30 min – 2 h in three brain regions ––frontal cortex (FC), ventromedial hypothalamus (VMH), and brain stem (BS). We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain. PMID:24416346

  8. NETopathies? Unraveling the Dark Side of Old Diseases through Neutrophils

    PubMed Central

    Mitsios, Alexandros; Arampatzioglou, Athanasios; Arelaki, Stella; Mitroulis, Ioannis; Ritis, Konstantinos

    2017-01-01

    Neutrophil extracellular traps (NETs) were initially described as an antimicrobial mechanism of neutrophils. Over the last decade, several lines of evidence support the involvement of NETs in a plethora of pathological conditions. Clinical and experimental data indicate that NET release constitutes a shared mechanism, which is involved in a different degree in various manifestations of non-infectious diseases. Even though the backbone of NETs is similar, there are differences in their protein load in different diseases, which represent alterations in neutrophil protein expression in distinct disorder-specific microenvironments. The characterization of NET protein load in different NET-driven disorders could be of significant diagnostic and/or therapeutic value. Additionally, it will provide further evidence for the role of NETs in disease pathogenesis, and it will enable the characterization of disorders in which neutrophils and NET-dependent inflammation are of critical importance. PMID:28123386

  9. Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

    PubMed

    Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

    2016-11-01

    The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair. This article reports the first in situ loading synchrotron studies on mechanical damage in collagenous tissues. We provide new insight into the nano- and micro-structural mechanisms of damage processes. Pre-damaged tendons showed differential alteration of moduli at macro, micro and nano-scales as measured using X-ray scattering techniques. Detailed analysis of higher order diffraction peaks suggested damage is localised to molecular cross-links. The results are consistent with previous X-ray scattering studies of tendons and also with recent thermal stability studies on damaged material. Detailed understanding of damage mechanisms is essential in the development of new therapies promoting tissue repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Evaluation of an injectable hydrogel and polymethyl methacrylate in restoring mechanics to compressively fractured spine motion segments.

    PubMed

    Balkovec, Christian; Vernengo, Andrea J; Stevenson, Peter; McGill, Stuart M

    2016-11-01

    Compressive fracture can produce profound changes to the mechanical profile of a spine segment. Minimally invasive repair has the potential to restore both function and structural integrity to an injured spine. Use of both hydrogels to address changes to the disc, combined with polymethyl methacrylate (PMMA) to address changes to the vertebral body, has the potential to facilitate repair. The purpose of this investigation was to determine if the combined use of hydrogel injection and PMMA could restore the mechanical profile of an axially injured spinal motion segment. This is a basic science study evaluating a combination of hydrogel injection and vertebroplasty on restoring mechanics to compressively injured porcine spine motion segments. Fourteen porcine spine motion segments were subject to axial compression until fracture using a dynamic servohydraulic testing apparatus. Rotational and compressive stiffness was measured for each specimen under the following conditions: initial undamaged, fractured, fatigue loading under compression, hydrogel injection, PMMA injection, and fatigue loading under compression. Group 1 received hydrogel injection followed by PMMA injection, whereas Group 2 received PMMA injection followed by hydrogel injection. This study was funded under a Natural Sciences and Engineering Research Council of Canada discovery grant. PMMA injection was found to alter the compressive stiffness properties of axially injured spine motion segments, restoring values from Groups 1 and 2 to 89.3%±29.3% and 81%±27.9% of initial values respectively. Hydrogel injection was found to alter the rotational stiffness properties, restoring specimens in Groups 1 and 2 to 151.5%±81% and 177.2%±54.9% of initial values respectively. Prolonged restoration of function was not possible, however, after further fatigue loading. Using this repair technique, replication of the mechanism of injury appears to cause a rapid deterioration in function of the motion segments. Containment of the hydrogel appears to be an issue with large breaches in the end plate, as it is posited to migrate into the cancellous bone of the vertebral body. Future work should attempt to evaluate methods in fully sealing the disc space. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The effect of creep on human lumbar intervertebral disk impact mechanics.

    PubMed

    Jamison, David; Marcolongo, Michele S

    2014-03-01

    The intervertebral disk (IVD) is a highly hydrated tissue, with interstitial fluid making up 80% of the wet weight of the nucleus pulposus (NP), and 70% of the annulus fibrosus (AF). It has often been modeled as a biphasic material, consisting of both a solid and fluid phase. The inherent porosity and osmotic potential of the disk causes an efflux of fluid while under constant load, which leads to a continuous displacement phenomenon known as creep. IVD compressive stiffness increases and NP pressure decreases as a result of creep displacement. Though the effects of creep on disk mechanics have been studied extensively, it has been limited to nonimpact loading conditions. The goal of this study is to better understand the influence of creep and fluid loss on IVD impact mechanics. Twenty-four human lumbar disk samples were divided into six groups according to the length of time they underwent creep (tcreep = 0, 3, 6, 9, 12, 15 h) under a constant compressive load of 400 N. At the end of tcreep, each disk was subjected to a sequence of impact loads of varying durations (timp = 80, 160, 320, 400, 600, 800, 1000 ms). Energy dissipation (ΔE), stiffness in the toe (ktoe) and linear (klin) regions, and neutral zone (NZ) were measured. Analyzing correlations with tcreep, there was a positive correlation with ΔE and NZ, along with a negative correlation with ktoe. There was no strong correlation between tcreep and klin. The data suggest that the IVD mechanical response to impact loading conditions is altered by fluid content and may result in a disk that exhibits less clinical stability and transfers more load to the AF. This could have implications for risk of diskogenic pain as a function of time of day or tissue hydration.

  12. Closed-form Static Analysis with Inertia Relief and Displacement-Dependent Loads Using a MSC/NASTRAN DMAP Alter

    NASA Technical Reports Server (NTRS)

    Barnett, Alan R.; Widrick, Timothy W.; Ludwiczak, Damian R.

    1995-01-01

    Solving for the displacements of free-free coupled systems acted upon by static loads is commonly performed throughout the aerospace industry. Many times, these problems are solved using static analysis with inertia relief. This solution technique allows for a free-free static analysis by balancing the applied loads with inertia loads generated by the applied loads. For some engineering applications, the displacements of the free-free coupled system induce additional static loads. Hence, the applied loads are equal to the original loads plus displacement-dependent loads. Solving for the final displacements of such systems is commonly performed using iterative solution techniques. Unfortunately, these techniques can be time-consuming and labor-intensive. Since the coupled system equations for free-free systems with displacement-dependent loads can be written in closed-form, it is advantageous to solve for the displacements in this manner. Implementing closed-form equations in static analysis with inertia relief is analogous to implementing transfer functions in dynamic analysis. Using a MSC/NASTRAN DMAP Alter, displacement-dependent loads have been included in static analysis with inertia relief. Such an Alter has been used successfully to solve efficiently a common aerospace problem typically solved using an iterative technique.

  13. Partial Reductions in Mechanical Loading Yield Proportional Changes in Bone Density, Bone Architecture, and Muscle Mass

    PubMed Central

    Ellman, Rachel; Spatz, Jordan; Cloutier, Alison; Palme, Rupert; Christiansen, Blaine A; Bouxsein, Mary L

    2014-01-01

    Although the musculoskeletal system is known to be sensitive to changes in its mechanical environment, the relationship between functional adaptation and below-normal mechanical stimuli is not well defined. We investigated bone and muscle adaptation to a range of reduced loading using the partial weight suspension (PWS) system, in which a two-point harness is used to offload a tunable amount of body weight while maintaining quadrupedal locomotion. Skeletally mature female C57Bl/6 mice were exposed to partial weight bearing at 20%, 40%, 70%, or 100% of body weight for 21 days. A hindlimb unloaded (HLU) group was included for comparison in addition to age-matched controls in normal housing. Gait kinematics was measured across the full range of weight bearing, and some minor alterations in gait from PWS were identified. With PWS, bone and muscle changes were generally proportional to the degree of unloading. Specifically, total body and hindlimb bone mineral density, calf muscle mass, trabecular bone volume of the distal femur, and cortical area of the femur midshaft were all linearly related to the degree of unloading. Even a load reduction to 70% of normal weight bearing was associated with significant bone deterioration and muscle atrophy. Weight bearing at 20% did not lead to better bone outcomes than HLU despite less muscle atrophy and presumably greater mechanical stimulus, requiring further investigation. These data confirm that the PWS model is highly effective in applying controllable, reduced, long-term loading that produces predictable, discrete adaptive changes in muscle and bone of the hindlimb. PMID:23165526

  14. Alteration of human umbilical vein endothelial cell gene expression in different biomechanical environments.

    PubMed

    Shoajei, Shahrokh; Tafazzoli-Shahdpour, Mohammad; Shokrgozar, Mohammad Ali; Haghighipour, Nooshin

    2014-05-01

    Biomechanical environments affect the function of cells. In this study we analysed the effects of five mechanical stimuli on the gene expression of human umbilical vein endothelial cells (HUVECs) in mRNA level using real-time PCR. The following loading regimes were applied on HUVECs for 48 h: intermittent (0-5 dyn/cm(2) , 1 Hz) and uniform (5 dyn/cm(2) ) shear stresses concomitant by 10% intermittent equiaxial stretch (1 Hz), uniform shear stress alone (5 dyn/cm(2) ), and intermittent uniaxial and equiaxial stretches (10%, 1 Hz). A new bioreactor was made to apply uniform/cyclic shear and tensile loadings. Three endothelial suggestive specific genes (vascular endothelial growth factor receptor-2 (VEGFR-2, also known as FLK-1), von Willebrand Factor (vWF) and vascular endothelial-cadherin (VE-cadherin)), and two smooth muscle genes (α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SMMHC)) were chosen for assessment of alteration in gene expression of endothelial cells and transdifferentiation toward smooth cells following load applications. Shear stress alone enhanced the endothelial gene expression significantly, while stretching alone was identified as a transdifferentiating factor. Cyclic equiaxial stretch contributed less to elevation of smooth muscle genes compared to uniaxial stretch. Cyclic shear stress in comparison to uniform shear stress concurrent with cyclic stretch was more influential on promotion of endothelial genes expression. Influence of different mechanical stimuli on gene expression may open a wider horizon to regulate functions of cell for tissue engineering purposes. © 2013 International Federation for Cell Biology.

  15. Extracellular matrix controls tubulin monomer levels in hepatocytes by regulating protein turnover

    NASA Technical Reports Server (NTRS)

    Mooney, D. J.; Hansen, L. K.; Langer, R.; Vacanti, J. P.; Ingber, D. E.

    1994-01-01

    Cells have evolved an autoregulatory mechanism to dampen variations in the concentration of tubulin monomer that is available to polymerize into microtubules (MTs), a process that is known as tubulin autoregulation. However, thermodynamic analysis of MT polymerization predicts that the concentration of free tubulin monomer must vary if MTs are to remain stable under different mechanical loads that result from changes in cell adhesion to the extracellular matrix (ECM). To determine how these seemingly contradictory regulatory mechanisms coexist in cells, we measured changes in the masses of tubulin monomer and polymer that resulted from altering cell-ECM contacts. Primary rat hepatocytes were cultured in chemically defined medium on bacteriological petri dishes that were precoated with different densities of laminin (LM). Increasing the LM density from low to high (1-1000 ng/cm2), promoted cell spreading (average projected cell area increased from 1200 to 6000 microns2) and resulted in formation of a greatly extended MT network. Nevertheless, the steady-state mass of tubulin polymer was similar at 48 h, regardless of cell shape or ECM density. In contrast, round hepatocytes on low LM contained a threefold higher mass of tubulin monomer when compared with spread cells on high LM. Furthermore, similar results were obtained whether LM, fibronectin, or type I collagen were used for cell attachment. Tubulin autoregulation appeared to function normally in these cells because tubulin mRNA levels and protein synthetic rates were greatly depressed in round cells that contained the highest level of free tubulin monomer. However, the rate of tubulin protein degradation slowed, causing the tubulin half-life to increase from approximately 24 to 55 h as the LM density was lowered from high to low and cell rounding was promoted. These results indicate that the set-point for the tubulin monomer mass in hepatocytes can be regulated by altering the density of ECM contacts and changing cell shape. This finding is consistent with a mechanism of MT regulation in which the ECM stabilizes MTs by both accepting transfer of mechanical loads and altering tubulin degradation in cells that continue to autoregulate tubulin synthesis.

  16. Focal cartilage defect compromises fluid-pressure dependent load support in the knee joint.

    PubMed

    Dabiri, Yaghoub; Li, LePing

    2015-06-01

    A focal cartilage defect involves tissue loss or rupture. Altered mechanics in the affected joint may play an essential role in the onset and progression of osteoarthritis. The objective of the present study was to determine the compromised load support in the human knee joint during defect progression from the cartilage surface to the cartilage-bone interface. Ten normal and defect cases were simulated with a previously tested 3D finite element model of the knee. The focal defects were considered in both condyles within high load-bearing regions. Fluid pressurization, anisotropic fibril-reinforcement, and depth-dependent mechanical properties were considered for the articular cartilages and menisci. The results showed that a small cartilage defect could cause 25% reduction in the load support of the knee joint due to a reduced capacity of fluid pressurization in the defect cartilage. A partial-thickness defect could cause a fluid pressure decrease or increase in the remaining underlying cartilage depending on the defect depth. A cartilage defect also increased the shear strain at the cartilage-bone interface, which was more significant with a full-thickness defect. The effect of cartilage defect on the fluid pressurization also depended on the defect sites and contact conditions. In conclusion, a focal cartilage defect causes a fluid-pressure dependent load reallocation and a compromised load support in the joint, which depend on the defect depth, site, and contact condition. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

    NASA Technical Reports Server (NTRS)

    Globus, Ruth K.; Searby, Nancy D.; Almeida, Eduardo A. C.; Sutijono, Darrell; Yu, Joon-Ho; Malouvier, Alexander; Doty, Steven B.; Morey-Holton, Emily; Weinstein, Steven L.; Dalton, Bonnie P. (Technical Monitor)

    2000-01-01

    Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We examined cell survival, reasoning that osteoblasts might mold skeletal structure in a hypergravity environment in part by regulating apoptosis and thus the duration of osteoblast productivity. Finally, we tested the influence of centrifugation on microbial activation of a macrophage cell line (RAW264.7). In response to the appropriate hormonal stimulation, this cell line is reportedly capable of undergoing differentiation to express osteoclast markers. In addition, a component of the cell wall of gram-negative bacteria, lipopolysaccaride (LPS), stimulates the formation of osteoclasts in vivo. Thus we tested the influence on centrifugation on RAW264.7 cells stimulated with LPS to provide an index of the function of osteoclast precursors.

  18. Altered expression of CD1d molecules and lipid accumulation in the human hepatoma cell line HepG2 after iron loading.

    PubMed

    Cabrita, Marisa; Pereira, Carlos F; Rodrigues, Pedro; Cardoso, Elsa M; Arosa, Fernando A

    2005-01-01

    Iron overload in the liver may occur in clinical conditions such as hemochromatosis and nonalcoholic steatohepatitis, and may lead to the deterioration of the normal liver architecture by mechanisms not well understood. Although a relationship between the expression of ICAM-1, and classical major histocompatibility complex (MHC) class I molecules, and iron overload has been reported, no relationship has been identified between iron overload and the expression of unconventional MHC class I molecules. Herein, we report that parameters of iron metabolism were regulated in a coordinated-fashion in a human hepatoma cell line (HepG2 cells) after iron loading, leading to increased cellular oxidative stress and growth retardation. Iron loading of HepG2 cells resulted in increased expression of Nor3.2-reactive CD1d molecules at the plasma membrane. Expression of classical MHC class I and II molecules, ICAM-1 and the epithelial CD8 ligand, gp180 was not significantly affected by iron. Considering that intracellular lipids regulate expression of CD1d at the cell surface, we examined parameters of lipid metabolism in iron-loaded HepG2 cells. Interestingly, increased expression of CD1d molecules by iron-loaded HepG2 cells was associated with increased phosphatidylserine expression in the outer leaflet of the plasma membrane and the presence of many intracellular lipid droplets. These data describe a new relationship between iron loading, lipid accumulation and altered expression of CD1d, an unconventional MHC class I molecule reported to monitor intracellular and plasma membrane lipid metabolism, in the human hepatoma cell line HepG2.

  19. The zebrafish as a novel animal model to study the molecular mechanisms of mechano-electrical feedback in the heart

    PubMed Central

    Werdich, Andreas A; Brzezinski, Anna; Jeyaraj, Darwin; Ficker, Eckhard; Wan, Xiaoping; McDermott, Brian M; Sabeh, M Khaled; MacRae, Calum A; Rosenbaum, David S

    2013-01-01

    Altered mechanical loading of the heart leads to hypertrophy, decompensated heart failure and fatal arrhythmias. However, the molecular mechanisms that link mechanical and electrical dysfunction remain poorly understood. Growing evidence suggest that ventricular electrical remodeling (VER) is a process that can be induced by altered mechanical stress, creating persistent electrophysiological changes that predispose the heart to life-threatening arrhythmias. While VER is clearly a physiological property of the human heart, as evidenced by “T wave memory”, it is also thought to occur in a variety of pathological states associated with altered ventricular activation such as bundle branch block, myocardial infarction, and cardiac pacing. Animal models that are currently being used for investigating stretch-induced VER have significant limitations. The zebrafish has recently emerged as an attractive animal model for studying cardiovascular disease and could overcome some of these limitations. Owing to its extensively sequenced genome, high conservation of gene function, and the comprehensive genetic resources that are available in this model, the zebrafish may provide new insights into the molecular mechanisms that drive detrimental electrical remodeling in response to stretch. Here, we have established a zebrafish model to study mechano-electrical feedback in the heart, which combines efficient genetic manipulation with high-precision stretch and high-resolution electrophysiology. In this model, only ninety minutes of ventricular stretch caused VER and recapitulated key features of VER found previously in the mammalian heart. Our data suggest that the zebrafish model is a powerful platform for investigating the molecular mechanisms underlying mechano-electrical feedback and VER in the heart. PMID:22835662

  20. Modeling the hydro-mechanical responses of strip and circular punch loadings on water-saturated collapsible geomaterials

    DOE PAGES

    Sun, WaiChing; Chen, Qiushi; Ostien, Jakob T.

    2013-11-22

    A stabilized enhanced strain finite element procedure for poromechanics is fully integrated with an elasto-plastic cap model to simulate the hydro-mechanical interactions of fluid-infiltrating porous rocks with associative and non-associative plastic flow. We present a quantitative analysis on how macroscopic plastic volumetric response caused by pore collapse and grain rearrangement affects the seepage of pore fluid, and vice versa. Results of finite element simulations imply that the dissipation of excess pore pressure may significantly affect the stress path and thus alter the volumetric plastic responses.

  1. Aquatic Exercise and Thermoregulation in Pregnancy.

    PubMed

    Soultanakis, Helen N

    2016-09-01

    Aquatic exercise, in a general sense, is any type of movement performed in the water for the purpose of improving health and fitness. Water, with its properties, provides buoyancy to lighten the "load" of pregnancy, hydrostatic pressure to alleviate pregnancy-induced edema, and many other benefits. Sports in extreme temperatures may involve some risks. The fact that a person's conductivity increases about 25 times in water comes with a great loss, which is the depression of the evaporative mechanism. Altered thermal control mechanisms in water, both in the gravid and the nongravid state, will be addressed in this review. convenience.

  2. Skeletal muscle contractions uncoupled from gravitational loading directly increase cortical bone blood flow rates in vivo.

    PubMed

    Caulkins, Carrie; Ebramzadeh, Edward; Winet, Howard

    2009-05-01

    The direct and indirect effects of muscle contraction on bone microcirculation and fluid flow are neither well documented nor explained. However, skeletal muscle contractions may affect the acquisition and maintenance of bone via stimulation of bone circulatory and interstitial fluid flow parameters. The purposes of this study were to assess the effects of transcutaneous electrical neuromuscular stimulation (TENS)-induced muscle contractions on cortical bone blood flow and bone mineral content, and to demonstrate that alterations in blood flow could occur independently of mechanical loading and systemic circulatory mechanisms. Bone chamber implants were used in a rabbit model to observe real-time blood flow rates and TENS-induced muscle contractions. Video recording of fluorescent microspheres injected into the blood circulation was used to calculate changes in cortical blood flow rates. TENS-induced repetitive muscle contractions uncoupled from mechanical loading instantaneously increased cortical microcirculatory flow, directly increased bone blood flow rates by 130%, and significantly increased bone mineral content over 7 weeks. Heart rates and blood pressure did not significantly increase due to TENS treatment. Our findings suggest that muscle contraction therapies have potential clinical applications for improving blood flow to cortical bone in the appendicular skeleton. Copyright 2008 Orthopaedic Research Society

  3. Achilles Tendon Properties of Minimalist and Traditionally Shod Runners.

    PubMed

    Histen, Katherine; Arntsen, Julia; L'Hereux, Lauren; Heeren, James; Wicki, Benjamin; Saint, Sterling; Aerni, Giselle; Denegar, Craig R; Joseph, Michael F

    2017-04-01

    Tendon adapts to load through alterations in its composition and mechanical properties. Mechanical adaptation to increased load often involves increases in cross-sectional area (CSA), stiffness, and modulus. Runners exhibit these adaptations. To determine if runners wearing minimalist shoes had larger and stiffer Achilles tendons (AT) than traditionally shod runners. Cross-sectional study of well-trained, traditionally and minimally shod runners. Laboratory assessment of trained runners. 23 men (11 traditional, 12 minimalist) and 8 women (6 traditional, 2 minimalist). Runners wearing minimalist shoes had 4.2 ± 1.6 y of training experience in minimalist shoes. The authors used diagnostic ultrasound and isokinetic dynamometry to generate a force-elongation curve and its derivatives. Minimalist runners had a greater CSA: mean difference (MD) = 9.2 mm 2 , stiffness (MD = 268.1 N/mm), and modulus (MD = 202.9 MPa). ATs of minimalist runners experienced greater stress (MD 8.6 N/mm 2 ) during maximal voluntary isometric contraction of the plantar-flexor muscles due to greater force of contraction (MD 798.9 N). The AT in minimalist runners adapts by increasing size, stiffness, and modulus, which is consistent with our understanding of mechanical adaptation of tendon to increased loading. Increased stress to the AT likely requires a slow transition to minimalist running to allow the AT to adapt without evidence of injury.

  4. Establishing Biomechanical Mechanisms in Mouse Models: Practical Guidelines for Systematically Evaluating Phenotypic Changes in the Diaphyses of Long Bones

    PubMed Central

    Jepsen, Karl J; Silva, Matthew J; Vashishth, Deepak; Guo, X Edward; van der Meulen, Marjolein CH

    2016-01-01

    Mice are widely used in studies of skeletal biology, and assessment of their bones by mechanical testing is a critical step when evaluating the functional effects of an experimental perturbation. For example, a gene knockout may target a pathway important in bone formation and result in a “low bone mass” phenotype. But how well does the skeleton bear functional loads; eg, how much do bones deform during loading and how resistant are bones to fracture? By systematic evaluation of bone morphological, densitometric, and mechanical properties, investigators can establish the “biomechanical mechanisms” whereby an experimental perturbation alters whole-bone mechanical function. The goal of this review is to clarify these biomechanical mechanisms and to make recommendations for systematically evaluating phenotypic changes in mouse bones, with a focus on long-bone diaphyses and cortical bone. Further, minimum reportable standards for testing conditions and outcome variables are suggested that will improve the comparison of data across studies. Basic biomechanical principles are reviewed, followed by a description of the cross-sectional morphological properties that best inform the net cellular effects of a given experimental perturbation and are most relevant to biomechanical function. Although morphology is critical, whole-bone mechanical properties can only be determined accurately by a mechanical test. The functional importance of stiffness, maximum load, postyield displacement, and work-to-fracture are reviewed. Because bone and body size are often strongly related, strategies to adjust whole-bone properties for body mass are detailed. Finally, a comprehensive framework is presented using real data, and several examples from the literature are reviewed to illustrate how to synthesize morphological, tissue-level, and whole-bone mechanical properties of mouse long bones. PMID:25917136

  5. Tumor-derived exosomes modulate T cell function through transfer of RNA.

    PubMed

    House, Imran G; Petley, Emma V; Beavis, Paul A

    2018-03-01

    Tumor cells can develop a variety of mechanisms to evade and subvert the immune system for their survival. Bland et al., in this edition of The FEBS Journal, make the novel finding that the tumor line B16F0 can deliver mRNA/miRNA loaded exosomes to cytotoxic T lymphocytes and alter their metabolic function and interferon gamma production. © 2018 Federation of European Biochemical Societies.

  6. Exercise does not enhance aged bone's impaired response to artificial loading in C57Bl/6 mice.

    PubMed

    Meakin, Lee B; Udeh, Chinedu; Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

    2015-12-01

    Bones adapt their structure to their loading environment and so ensure that they become, and are maintained, sufficiently strong to withstand the loads to which they are habituated. The effectiveness of this process declines with age and bones become fragile fracturing with less force. This effect in humans also occurs in mice which experience age-related bone loss and reduced adaptation to loading. Exercise engenders many systemic and local muscular physiological responses as well as engendering local bone strain. To investigate whether these physiological responses influence bones' adaptive responses to mechanical strain we examined whether a period of treadmill exercise influenced the adaptive response to an associated period of artificial loading in young adult (17-week) and old (19-month) mice. After treadmill acclimatization, mice were exercised for 30 min three times per week for two weeks. Three hours after each exercise period, right tibiae were subjected to 40 cycles of non-invasive axial loading engendering peak strain of 2250 με. In both young and aged mice exercise increased cross-sectional muscle area and serum sclerostin concentration. In young mice it also increased serum IGF1. Exercise did not affect bone's adaptation to loading in any measured parameter in young or aged bone. These data demonstrate that a level of exercise sufficient to cause systemic changes in serum, and adaptive changes in local musculature, has no effect on bone's response to loading 3h later. This study provides no support for the beneficial effects of exercise on bone in the elderly being mediated by systemic or local muscle-derived effects rather than local adaptation to altered mechanical strain. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  7. METABOLIC EFFECTS OF ANGULATION, COMPRESSION AND REDUCED MOBILITY ON ANNULUS FIBROSIS IN A MODEL OF ALTERED MECHANICAL ENVIRONMENT IN SCOLIOSIS

    PubMed Central

    Stokes, Ian A.F.; McBride, Carole; Aronsson, David D.; Roughley, Peter J.

    2013-01-01

    Study Design Comparison of disc tissue from rat tails in six groups having different mechanical conditions imposed. Objectives To identify disc annulus changes associated with the supposed altered biomechanical environment in a spine with scoliosis deformity using an immature rat model that produces disc narrowing and wedging. Background Intervertebral discs become wedged and narrowed in a scoliosis curve, probably due in part to altered biomechanical environment. Methods Tail discs of 5-week-old immature Sprague-Dawley rats were subjected to an altered mechanical environment using an external apparatus applying permutations of loading and deformity for 5 weeks. Four groups of rats (A) 15 degrees Angulation, (B) Angulation with 0.1 MPa Compression, (C) 0.1 MPa Compression, and (R) Reduced mobility, together with a sham and a control group were studied. Disc height changes and matrix composition (water, DNA, GAG and HA content) were measured after 5 weeks, and proline and sulphate incorporation and mRNA expression were measured at 5 days and 5 weeks. Results After 5 weeks, disc space was significantly narrowed relative to internal controls in all four intervention groups. Water content and cellularity (DNA content) were not different at interventional levels relative to internal controls and not different between the concave and convex sides of the angulated discs. There was increased GAG content in compressed tissue (in Groups B and C), as expected, and compression resulted in a decrease in hyaluronic acid size. Slightly increased incorporation of tritiated-proline into the concave side of angulated discs and compressed discs was observed. Asymmetries of gene expression in Groups A and B, and some group-wise differences, did not identify consistent patterns associating the discs’ responses to mechanical alterations. Conclusions Intervertebral discs in this model underwent substantial narrowing after 5 weeks, with minimal alteration in tissue composition and minimal evidence of metabolic changes. PMID:27927288

  8. Fluid load support and contact mechanics of hemiarthroplasty in the natural hip joint.

    PubMed

    Pawaskar, Sainath Shrikant; Ingham, Eileen; Fisher, John; Jin, Zhongmin

    2011-01-01

    The articular cartilage covering the ends of the bones of diarthrodial synovial joints is thought to have evolved so that the loads are transferred under different and complex conditions, with a very high degree of efficiency and without compromising the structural integrity of the tissue for the life of an individual. These loading conditions stem from different activities such as walking, and standing. The integrity of cartilage may however become compromised due to congenital disease, arthritis or trauma. Hemiarthroplasty is a potentially conservative treatment when only the femoral cartilage is affected as in case of femoral neck fractures. In hemiarthroplasty, a metallic femoral prosthesis is used to articulate against the natural acetabular cartilage. It has also been hypothesized that biphasic lubrication is the predominant mechanism protecting the cartilage through a very high fluid load support which lowers friction. This may be altered due to hemiarthroplasty and have a direct effect on the frictional shear stresses and potentially cartilage degradation and wear. This study modelled nine activities of daily living and investigated the contact mechanics of a hip joint with a hemiarthroplasty, focussing particularly on the role of the fluid phase. It was shown that in most of the activities studied the peak contact stresses and peak fluid pressures were in the superior dome or lateral roof of the acetabulum. Total fluid load support was very high (~90%) in most of the activities which would shield the solid phase from being subjected to very high contact stresses. This was dependent not only on the load magnitude but also the direction and hence on the location of the contact area with respect to the cartilage coverage. Lower fluid load support was found when the contact area was nearer the edges where the fluid drained easily. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  9. Molecular dynamics simulations of heterogeneous cell membranes in response to uniaxial membrane stretches at high loading rates.

    PubMed

    Zhang, Lili; Zhang, Zesheng; Jasa, John; Li, Dongli; Cleveland, Robin O; Negahban, Mehrdad; Jérusalem, Antoine

    2017-08-16

    The chemobiomechanical signatures of diseased cells are often distinctively different from that of healthy cells. This mainly arises from cellular structural/compositional alterations induced by disease development or therapeutic molecules. Therapeutic shock waves have the potential to mechanically destroy diseased cells and/or increase cell membrane permeability for drug delivery. However, the biomolecular mechanisms by which shock waves interact with diseased and healthy cellular components remain largely unknown. By integrating atomistic simulations with a novel multiscale numerical framework, this work provides new biomolecular mechanistic perspectives through which many mechanosensitive cellular processes could be quantitatively characterised. Here we examine the biomechanical responses of the chosen representative membrane complexes under rapid mechanical loadings pertinent to therapeutic shock wave conditions. We find that their rupture characteristics do not exhibit significant sensitivity to the applied strain rates. Furthermore, we show that the embedded rigid inclusions markedly facilitate stretch-induced membrane disruptions while mechanically stiffening the associated complexes under the applied membrane stretches. Our results suggest that the presence of rigid molecules in cellular membranes could serve as "mechanical catalysts" to promote the mechanical destructions of the associated complexes, which, in concert with other biochemical/medical considerations, should provide beneficial information for future biomechanical-mediated therapeutics.

  10. Fascicles from energy-storing tendons show an age-specific response to cyclic fatigue loading

    PubMed Central

    Thorpe, Chavaunne T.; Riley, Graham P.; Birch, Helen L.; Clegg, Peter D.; Screen, Hazel R. C.

    2014-01-01

    Some tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), act as energy stores, stretching and recoiling to increase efficiency during locomotion. Our previous observations of rotation in response to applied strain in SDFT fascicles suggest a helical structure, which may provide energy-storing tendons with a greater ability to extend and recoil efficiently. Despite this specialization, energy-storing tendons are prone to age-related tendinopathy. The aim of this study was to assess the effect of cyclic fatigue loading (FL) on the microstructural strain response of SDFT fascicles from young and old horses. The data demonstrate two independent age-related mechanisms of fatigue failure; in young horses, FL caused low levels of matrix damage and decreased rotation. This suggests that loading causes alterations to the helix substructure, which may reduce their ability to recoil and recover. By contrast, fascicles from old horses, in which the helix is already compromised, showed greater evidence of matrix damage and suffer increased fibre sliding after FL, which may partially explain the age-related increase in tendinopathy. Elucidation of helix structure and the precise alterations occurring owing to both ageing and FL will help to develop appropriate preventative and repair strategies for tendinopathy. PMID:24402919

  11. Advances in helical stent design and fabrication thermal treatment and structural interaction studies of the simulated plaque-laden artery

    NASA Astrophysics Data System (ADS)

    Welch, Tre Raymond

    Advancements in processing biomaterials have lead to the development of bioresorbable PLLA drug-loaded stents with different geometric configurations. To further advance the technology, systematic studies have been carried out. This dissertation consists of five specific aims: (1) To characterize the effects of thermal annealing on the mechanical characteristics of PLLA helical stent, (2) To characterize the mechanical characteristics of a PLLA double helix stent, (3) To characterize the physical and chemical properties of PLLA films impregnated with niacin and curcumin, (4) To characterize the mechanical interaction of expanded stent and vascular wall with both model simulation and experimental studies using PDMS phantom arteries, (5) To simulate the stent-plaque-artery interactions using computer models. Results and their significances in bioresorbable PLLA drug-loaded stents technology as well as clinical prospects will be presented. For Aim1, thermal annealing is shown to improve mechanical characteristics of the helical stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Differential scanning calorimetric analysis of stent fiber reveals that thermal annealing contribute to increased percent crystallinity, thus enhanced mechanical characteristics of the stent. For Aim 2, the new double helix design was shown to leads to improved mechanical characteristics of stent, including pressure-diameter response curves, incremental stiffness, and collapse pressure. Further, it was found to lead to an increased percent crystallinity and reduced degradation rate. For Aim 3, the changes in mechanical properties, crystallinity in PLLA polymer loaded with curcumin, or niacin, or both from that of control are clearly delineated. Results from Aim 4 shed lights on the mechanical disturbance in the vicinity of deployed stent and vascular wall as well as the abnormal shear stresses on the vascular endothelium. Their implications in triggering thrombi formation are discussed. Results from Aim 5 provided insights on the stent-plaque-artery mechanical interaction and how the altered mechanical environment after stent deployment could affect vascular remodeling and factors lead to re-stenosis. The significances of this work in advancing the bioresorbable PLLA drug-loaded stents technology as well as its clinical prospects are presented.

  12. Respiratory load perception in overweight and asthmatic children.

    PubMed

    MacBean, Victoria; Wheatley, Lorna; Lunt, Alan C; Rafferty, Gerrard F

    2017-05-01

    Overweight asthmatic children report greater symptoms than normal weight asthmatics, despite comparable airflow obstruction. This has been widely assumed to be due to heightened perception of respiratory effort. Three groups of children (healthy weight controls, healthy weight asthmatics, overweight asthmatics) rated perceived respiratory effort throughout an inspiratory resistive loading protocol. Parasternal intercostal electromyogram was used as an objective marker of respiratory load; this was expressed relative to tidal volume and reported as a ratio of the baseline value (neuroventilatory activity ratio (NVEAR)). Significant increases in perception scores (p<0.0001), and decreases in NVEAR (p<0.0001) were observed from lowest to highest resistive load. Higher BMI increased overall perception scores, with no influence of asthma or BMI-for-age percentile on the resistance-perception relationships. These data, indicating elevated overall respiratory effort in overweight asthmatic children but comparable responses to dynamic changes in load, suggest that the greater disease burden in overweight asthmatic children may be due to altered respiratory mechanics associated with increased body mass. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation.

    PubMed

    Ibrahim, Michael; Kukadia, Punam; Siedlecka, Urszula; Cartledge, James E; Navaratnarajah, Manoraj; Tokar, Sergiy; Van Doorn, Carin; Tsang, Victor T; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

    2012-12-01

    Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca(2+)-induced Ca(2+) release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart-lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca(2+) release synchronicity was reduced at 8 weeks moderate unloading only. Ca(2+) sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca(2+) transient, increased Ca(2+) spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  14. Periodontal Ligament Entheses and their Adaptive Role in the Context of Dentoalveolar Joint Function

    PubMed Central

    Lin, Jeremy D.; Jang, Andrew T.; Kurylo, Michael P.; Hurng, Jonathan; Yang, Feifei; Yang, Lynn; Pal, Arvin; Chen, Ling; Ho, Sunita P.

    2017-01-01

    Objectives The dynamic bone-periodontal ligament (PDL)-tooth fibrous joint consists of two adaptive functionally graded interfaces (FGI), the PDL-bone and PDL-cementum that respond to mechanical strain transmitted during mastication. In general, from a materials and mechanics perspective, FGI prevent catastrophic failure during prolonged cyclic loading. This review is a discourse of results gathered from literature to illustrate the dynamic adaptive nature of the fibrous joint in response to physiologic and pathologic simulated functions, and experimental tooth movement. Methods Historically, studies have investigated soft to hard tissue transitions through analytical techniques that provided insights into structural, biochemical, and mechanical characterization methods. Experimental approaches included two dimensional to three dimensional advanced in situ imaging and analytical techniques. These techniques allowed mapping and correlation of deformations to physicochemical and mechanobiological changes within volumes of the complex subjected to concentric and eccentric loading regimes respectively. Results Tooth movement is facilitated by mechanobiological activity at the interfaces of the fibrous joint and generates elastic discontinuities at these interfaces in response to eccentric loading. Both concentric and eccentric loads mediated cellular responses to strains, and prompted self-regulating mineral forming and resorbing zones that in turn altered the functional space of the joint. Significance A multiscale biomechanics and mechanobiology approach is important for correlating joint function to tissue-level strain-adaptive properties with overall effects on joint form as related to physiologic and pathologic functions. Elucidating the shift in localization of biomolecules specifically at interfaces during development, function, and therapeutic loading of the joint is critical for developing “functional regeneration and adaptation” strategies with an emphasis on restoring physiologic joint function. PMID:28476202

  15. Gait alterations can reduce the risk of edge loading.

    PubMed

    Wesseling, Mariska; Meyer, Christophe; De Groote, Friedl; Corten, Kristoff; Simon, Jean-Pierre; Desloovere, Kaat; Jonkers, Ilse

    2016-06-01

    Following metal-on-metal hip arthroplasty, edge loading (i.e., loading near the edge of a prosthesis cup) can increase wear and lead to early revision. The position and coverage angle of the prosthesis cup influence the risk of edge loading. This study investigates the effect of altered gait patterns, more specific hip, and pelvis kinematics, on the orientation of hip contact force and the consequent risk of antero-superior edge loading using muscle driven simulations of gait. With a cup orientation of 25° anteversion and 50° inclination and a coverage angle of 168°, many gait patterns presented risk of edge loading. Specifically at terminal double support, 189 out of 405 gait patterns indicated a risk of edge loading. At this time instant, the high hip contact forces and the proximity of the hip contact force to the edge of the cup indicated the likelihood of the occurrence of edge loading. Although the cup position contributed most to edge loading, altering kinematics considerably influenced the risk of edge loading. Increased hip abduction, resulting in decreasing hip contact force magnitude, and decreased hip extension, resulting in decreased risk on edge loading, are gait strategies that could prevent edge loading. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1069-1076, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  16. Bone tissue engineering: the role of interstitial fluid flow

    NASA Technical Reports Server (NTRS)

    Hillsley, M. V.; Frangos, J. A.

    1994-01-01

    It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

  17. Variable stiffness mechanisms with SMA actuators

    NASA Astrophysics Data System (ADS)

    Siler, Damin J.; Demoret, Kimberly B. J.

    1996-05-01

    Variable stiffness is a new branch of smart structures development with several applications related to aircraft. Previous research indicates that temporarily reducing the stiffness of an airplane wing can decrease control actuator sizing and improve aeroelastic roll performance. Some smart materials like shape memory alloys (SMA) can change their material stiffness properties, but they tend to gain stiffness in their `power on' state. An alternative is to integrate mechanisms into a structure and change stiffness by altering boundary conditions and structural load paths. An innovative concept for an axial strut mechanism was discovered as part of research into variable stiffness. It employs SMA springs (specifically Ni-Ti) in a way that reduces overall stiffness when the SMA springs gain stiffness. A simplified mathematical model for static analysis was developed, and a 70% reduction in stiffness was obtained for a particular selection of springs. The small force capacity of commercially available SMA springs limits the practicality of this concept for large load applications. However, smart material technology is still immature, and future advances may permit development of a heavy-duty, variable stiffness strut that is small and light enough for use in aircraft structures.

  18. Calcium-independent metal-ion catalytic mechanism of anthrax edema factor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shen, Yuequan; Zhukovskaya, Natalia L.; Guo, Qing

    2009-11-18

    Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen-binding domain (PABD) and a calmodulin (CaM)-activated adenylyl cyclase domain. Here, we report the crystal structures of CaM-bound EF, revealing the architecture of EF PABD. CaM has N- and C-terminal domains and each domain can bind two calcium ions. Calcium binding induces the conformational change of CaM from closed to open. Structures of the EF-CaM complex show how EF locks the N-terminal domain of CaM into a closed conformation regardless of its calcium-loading state. This represents a mechanism of how CaM effector alters the calcium affinity of CaM andmore » uncouples the conformational change of CaM from calcium loading. Furthermore, structures of EF-CaM complexed with nucleotides show that EF uses two-metal-ion catalysis, a prevalent mechanism in DNA and RNA polymerases. A histidine (H351) further facilitates the catalysis of EF by activating a water to deprotonate 3'OH of ATP. Mammalian adenylyl cyclases share no structural similarity with EF and they also use two-metal-ion catalysis, suggesting the catalytic mechanism-driven convergent evolution of two structurally diverse adenylyl cyclases.« less

  19. Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

    NASA Technical Reports Server (NTRS)

    Baldwin, Kenneth M.; Haddad, Fadia

    2002-01-01

    The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

  20. Osteoarthritis Year in Review 2015: Mechanics

    PubMed Central

    Varady, Nathan H.; Grodzinsky, Alan J.

    2015-01-01

    Motivated by the conceptual framework of multi-scale biomechanics, this narrative review highlights recent major advances with a focus on gait and joint kinematics, then tissue-level mechanics, cell mechanics and mechanotransduction, matrix mechanics, and finally the nanoscale mechanics of matrix macromolecules. A literature review was conducted from January 2014 to April 2015 using PubMed to identify major developments in mechanics related to osteoarthritis (OA). Studies of knee adduction, flexion, rotation, and contact mechanics have extended our understanding of medial compartment loading. In turn, advances in measurement methodologies have shown how injuries to both the meniscus and ligaments, together, can alter joint kinematics. At the tissue scale, novel findings have emerged regarding the mechanics of the meniscus as well as cartilage superficial zone. Moving to the cell level, poroelastic and poroviscoelastic mechanisms underlying chondrocyte deformation have been reported, along with the response to osmotic stress. Further developments have emerged on the role of calcium signaling in chondrocyte mechanobiology, including exciting findings on the function of mechanically activated cation channels newly found to be expressed in chondrocytes. Finally, AFM-based nano-rheology systems have enabled studies of thin murine tissues and brush layers of matrix molecules over a wide range of loading rates including high rates corresponding to impact injury. With OA acknowledged to be a disease of the joint as an organ, understanding mechanical behavior at each length scale helps to elucidate the connections between cell biology, matrix biochemistry and tissue structure/function that may play a role in the pathomechanics of OA. PMID:26707990

  1. Small Crack Growth and Its Influence in Near Alpha-Titanium Alloys

    DTIC Science & Technology

    1989-06-01

    geometries via finite element and boundary-collocation analysis 8 , 9 . Elastic plastic fracture mechanics ( EPFM ) 1 0 , 1 1 and local crack tip field...correlation was found between experimental and predicted data, general application of the model is not possible as both 0 and rp are sensitive to changes in...cracks at low AK the load reduction schemes should be altered to remove the residual deformations, perhaps via machining or the application of large

  2. BMP delivery complements the guiding effect of scaffold architecture without altering bone microstructure in critical-sized long bone defects: A multiscale analysis.

    PubMed

    Cipitria, A; Wagermaier, W; Zaslansky, P; Schell, H; Reichert, J C; Fratzl, P; Hutmacher, D W; Duda, G N

    2015-09-01

    Scaffold architecture guides bone formation. However, in critical-sized long bone defects additional BMP-mediated osteogenic stimulation is needed to form clinically relevant volumes of new bone. The hierarchical structure of bone determines its mechanical properties. Yet, the micro- and nanostructure of BMP-mediated fast-forming bone has not been compared with slower regenerating bone without BMP. We investigated the combined effects of scaffold architecture (physical cue) and BMP stimulation (biological cue) on bone regeneration. It was hypothesized that a structured scaffold directs tissue organization through structural guidance and load transfer, while BMP stimulation accelerates bone formation without altering the microstructure at different length scales. BMP-loaded medical grade polycaprolactone-tricalcium phosphate scaffolds were implanted in 30mm tibial defects in sheep. BMP-mediated bone formation after 3 and 12 months was compared with slower bone formation with a scaffold alone after 12 months. A multiscale analysis based on microcomputed tomography, histology, polarized light microscopy, backscattered electron microscopy, small angle X-ray scattering and nanoindentation was used to characterize bone volume, collagen fiber orientation, mineral particle thickness and orientation, and local mechanical properties. Despite different observed kinetics in bone formation, similar structural properties on a microscopic and sub-micron level seem to emerge in both BMP-treated and scaffold only groups. The guiding effect of the scaffold architecture is illustrated through structural differences in bone across different regions. In the vicinity of the scaffold increased tissue organization is observed at 3 months. Loading along the long bone axis transferred through the scaffold defines bone micro- and nanostructure after 12 months. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart.

    PubMed

    Sung, Derrick; Mills, Robert W; Schettler, Jan; Narayan, Sanjiv M; Omens, Jeffrey H; McCulloch, Andrew D

    2003-07-01

    Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  4. Characterizing depth-dependent refractive index of articular cartilage subjected to mechanical wear or enzymic degeneration

    NASA Astrophysics Data System (ADS)

    Wang, Kuyu; Wu, Jianping; Day, Robert; Kirk, Thomas Brett; Hu, Xiaozhi

    2016-09-01

    Utilizing a laser scanning confocal microscope system, the refractive indices of articular cartilage (AC) with mechanical or biochemical degenerations were characterized to investigate whether potential correlations exist between refractive index (RI) and cartilage degeneration. The cartilage samples collected from the medial femoral condyles of kangaroo knees were mechanically degenerated under different loading patterns or digested in trypsin solution with different concentrations. The sequences of RI were then measured from cartilage surface to deep region and the fluctuations of RI were quantified considering combined effects of fluctuating frequency and amplitude. The compositional and microstructural alterations of cartilage samples were assessed with histological methods. Along with the loss of proteoglycans, the average RI of cartilage increased and the local fluctuation of RI became stronger. Short-term high-speed test induced little influence to both the depth fluctuation and overall level of RI. Long-term low-speed test increased the fluctuation of RI but the average RI was barely changed. The results substantially demonstrate that RI of AC varies with both compositional and structural alterations and is potentially an indicator for the degeneration of AC.

  5. Building Finite Element Models to Investigate Zebrafish Jaw Biomechanics.

    PubMed

    Brunt, Lucy H; Roddy, Karen A; Rayfield, Emily J; Hammond, Chrissy L

    2016-12-03

    Skeletal morphogenesis occurs through tightly regulated cell behaviors during development; many cell types alter their behavior in response to mechanical strain. Skeletal joints are subjected to dynamic mechanical loading. Finite element analysis (FEA) is a computational method, frequently used in engineering that can predict how a material or structure will respond to mechanical input. By dividing a whole system (in this case the zebrafish jaw skeleton) into a mesh of smaller 'finite elements', FEA can be used to calculate the mechanical response of the structure to external loads. The results can be visualized in many ways including as a 'heat map' showing the position of maximum and minimum principal strains (a positive principal strain indicates tension while a negative indicates compression. The maximum and minimum refer the largest and smallest strain). These can be used to identify which regions of the jaw and therefore which cells are likely to be under particularly high tensional or compressional loads during jaw movement and can therefore be used to identify relationships between mechanical strain and cell behavior. This protocol describes the steps to generate Finite Element models from confocal image data on the musculoskeletal system, using the zebrafish lower jaw as a practical example. The protocol leads the reader through a series of steps: 1) staining of the musculoskeletal components, 2) imaging the musculoskeletal components, 3) building a 3 dimensional (3D) surface, 4) generating a mesh of Finite Elements, 5) solving the FEA and finally 6) validating the results by comparison to real displacements seen in movements of the fish jaw.

  6. Thermo-mechanical modelling of salt caverns due to fluctuating loading conditions.

    NASA Astrophysics Data System (ADS)

    Böttcher, N.

    2015-12-01

    This work summarizes the development and application of a numerical model for the thermo-mechanical behaviour of salt caverns during cyclic gas storage. Artificial salt caverns are used for short term energy storage, such as power-to-gas or compressed air energy storage. Those applications are characterized by highly fluctuating operation pressures due to the unsteady power levels of power plants based on renewable energy. Compression and expansion of the storage gases during loading and unloading stages lead to rapidly changing temperatures in the host rock of the caverns. This affects the material behaviour of the host rock within a zone that extends several meters into the rock mass adjacent to the cavern wall, and induces thermo-mechanical stresses and alters the creep response.The proposed model features the thermodynamic behaviour of the storage medium, conductive heat transport in the host rock, as well as temperature dependent material properties of rock salt using different thermo-viscoplastic material models. The utilized constitutive models are well known and state-of-the-art in various salt mechanics applications. The model has been implemented into the open-source software platform OpenGeoSys. Thermal and mechanical processes are solved using a finite element approach, coupled via a staggered coupling scheme. The simulation results allow the conclusion, that the cavern convergence rate (and thus the efficiency of the cavern) is highly influenced by the loading cycle frequency and the resulting gas temperatures. The model therefore allows to analyse the influence of operation modes on the cavern host rock or on neighbouring facilities.

  7. Effect of Grinding and Multi-Stimuli Aging on the Fatigue Strength of a Y-TZP Ceramic.

    PubMed

    Silvestri, Tais; Pereira, Gabriel Kalil Rocha; Guilardi, Luis Felipe; Rippe, Marilia Pivetta; Valandro, Luiz Felipe

    2018-01-01

    This study aimed to investigate the effect of grinding and multi-stimuli aging on the fatigue strength, surface topography and the phase transformation of Y-TZP ceramic. Discs were manufactured according to ISO-6872:2008 for biaxial flexure testing (diameter: 15 mm; thickness: 1.2 mm) and randomly assigned considering two factors "grinding" and "aging": C- control (as-sintered); CA- control + aging; G- ground; GA- ground + aging. Grinding was carried out with coarse diamond burs under water-cooling. Aging protocols consisted of: autoclave (134°C, 2 bars pressure, 20 hours), followed by storage for 365 days (samples were kept untouched at room temperature), and by mechanical cycling (106 cycles by 20 Hz under a load of 50% from the biaxial flexure monotonic tests). Flexural fatigue strengths (20,000 cycles; 6 Hz) were determined under sinusoidal cyclic loading using staircase approach. Additionally, surface topography analysis by FE-SEM and phase transformation analysis by X-ray Diffractometry were performed. Dixon and Mood methodology was used to analyze the fatigue strength data. Grinding promotes alterations of topographical pattern, while aging apparently did not alter it. Grinding triggered t-m phase transformation without impacting the fatigue strength of the Y-TZP ceramic; and aging promoted an intense t-m transformation that resulted in a toughening mechanism leading to higher fatigue strength for as-sintered condition, and a tendency of increase for ground condition (C < CA; G = GA). It concludes that grinding and aging procedures did not affect deleteriously the fatigue strength of the evaluated Y-TZP ceramic, although, it promotes surface topography alterations, except to aging, and t-m phase transformation.

  8. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

    PubMed

    Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

    2016-01-01

    Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

  9. Mechanical changes caused by CO2-driven cement dissolution in the Morrow B Sandstone at reservoir conditions: Experimental observations

    NASA Astrophysics Data System (ADS)

    Wu, Z.; Luhmann, A. J.; Rinehart, A. J.; Mozley, P.; Dewers, T. A.

    2017-12-01

    Carbon Capture, Utilization and Storage (CCUS) in transmissive reservoirs is a proposed mechanism in reducing CO2 emissions. Injection of CO2 perturbs reservoir chemistry, and can modify porosity and permeability and alter mineralogy. However, little work has been done on the coupling of rock alteration by CO2 injection and the mechanical integrity of the reservoir. In this study, we perform flow-through experiments on calcite- and dolomite-cemented Pennsylvanian Morrow B Sandstone (West Texas, USA) cores. We hypothesize that poikilotopic calcite cement has a larger impact on chemo-mechanical alteration than disseminated dolomite cement given similar CO2 exposure. With one control brine flow-through experiment and two CO2-plus-brine flow-through experiments for each cement composition, flow rates of 0.1 and 0.01 ml/min were applied under 4200 psi pore fluid pressure and 5000 psi confining pressure at 71 °C. Fluid chemistry and permeability data enable monitoring of mineral dissolution. Ultrasonic velocities were measured pre-test using 1.2 MHz source-receiver pairs at 0.5 MPa axial load and show calcite-cemented samples with higher dynamic elastic moduli than dolomite-cemented samples. Velocities measured post-experiment will identify changes from fluid-rock interaction. We plan to conduct cylinder-splitting destructive mechanical test (Brazil test) to measure the pristine and altered tensile strength of different cemented sandstones. The experiments will identify extents to which cement composition and texture control chemo-mechanical degradation of CCUS reservoirs. Funding for this project is provided by the U.S. Department of Energy's (DOE) National Energy Technology Laboratory (NETL) through the Southwest Regional Partnership on Carbon Sequestration (SWP) under Award No. DE-FC26-05NT42591. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc. for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525.

  10. Working memory load modulation of parieto-frontal connections: evidence from dynamic causal modeling

    PubMed Central

    Ma, Liangsuo; Steinberg, Joel L.; Hasan, Khader M.; Narayana, Ponnada A.; Kramer, Larry A.; Moeller, F. Gerard

    2011-01-01

    Previous neuroimaging studies have shown that working memory load has marked effects on regional neural activation. However, the mechanism through which working memory load modulates brain connectivity is still unclear. In this study, this issue was addressed using dynamic causal modeling (DCM) based on functional magnetic resonance imaging (fMRI) data. Eighteen normal healthy subjects were scanned while they performed a working memory task with variable memory load, as parameterized by two levels of memory delay and three levels of digit load (number of digits presented in each visual stimulus). Eight regions of interest, i.e., bilateral middle frontal gyrus (MFG), anterior cingulate cortex (ACC), inferior frontal cortex (IFC), and posterior parietal cortex (PPC), were chosen for DCM analyses. Analysis of the behavioral data during the fMRI scan revealed that accuracy decreased as digit load increased. Bayesian inference on model structure indicated that a bilinear DCM in which memory delay was the driving input to bilateral PPC and in which digit load modulated several parieto-frontal connections was the optimal model. Analysis of model parameters showed that higher digit load enhanced connection from L PPC to L IFC, and lower digit load inhibited connection from R PPC to L ACC. These findings suggest that working memory load modulates brain connectivity in a parieto-frontal network, and may reflect altered neuronal processes, e.g., information processing or error monitoring, with the change in working memory load. PMID:21692148

  11. Stepwise morphological changes and cytoskeletal reorganization of human mesenchymal stem cells treated by short-time cyclic uniaxial stretch.

    PubMed

    Parandakh, Azim; Tafazzoli-Shadpour, Mohammad; Khani, Mohammad-Mehdi

    2017-06-01

    This study aimed to investigate stepwise remodeling of human mesenchymal stem cells (hMSCs) in response to cyclic stretch through rearrangement and alignment of cells and cytoskeleton regulation toward smooth muscle cell (SMC) fate in different time spans. Image analysis techniques were utilized to calculate morphological parameters. Cytoskeletal reorganization was observed by investigating F-actin filaments using immunofluorescence staining, and expression level of contractile SMC markers was followed by a quantitative polymerase chain reaction method. Applying cyclic uniaxial stretch on cultured hMSCs, utilizing a costume-made device, led to alteration in fractal dimension (FD) and cytoskeleton structure toward continuous alignment and elongation of cells by elevation of strain duration. Actin filaments became more aligned perpendicular to the axis of mechanical stretch by increasing uniaxial loading duration. At first, FD met a significant decrease in 4 h loading duration then increased significantly by further loading up to 16 h, followed by another decrease up to 1 d of uniaxial stretching. HMSCs subjected to 24 h cyclic uniaxial stretching significantly expressed early and intermediate contractile SM markers. It was hypothesized that the increase in FD after 4 h while cells continuously became more aligned and elongated was due to initiation of change in phenotype that influenced arrangement of cells. At this point, change in cell phenotype started leading to change in morphology while mechanical loading still caused cell alignment and rearrangement. Results can be helpful when optimized engineered cells are needed based on mechanical condition for functional engineered tissue and cell therapy.

  12. Tactile perception of skin and skin cream by friction induced vibrations.

    PubMed

    Ding, Shuyang; Bhushan, Bharat

    2016-11-01

    Skin cream smooths, softens, and moistens skin by altering surface roughness and tribological properties of skin. Sliding generates vibrations that activate mechanoreceptors located in skin. The brain interprets tactile information to identify skin feel. Understanding the tactile sensing mechanisms of skin with and without cream treatment is important to numerous applications including cosmetics, textiles, and robotics sensors. In this study, frequency spectra of friction force and friction induced vibration signals were carried out to investigate tactile perception by an artificial finger sliding on skin. The influence of normal load, velocity, and cream treatment time were studied. Coherence between friction force and vibration signals were found. The amplitude of vibration decreased after cream treatment, leading to smoother perception. Increasing normal load or velocity between contacting surfaces generated a smoother perception with cream treatment, but rougher perception without treatment. As cream treatment time increases, skin becomes smoother. The related mechanisms are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The radiation of sound from a propeller at angle of attack

    NASA Technical Reports Server (NTRS)

    Mani, Ramani

    1990-01-01

    The mechanism by which the noise generated at the blade passing frequency by a propeller is altered when the propeller axis is at an angle of attack to the freestream is examined. The measured noise field is distinctly non axially symmetric under such conditions with far field sound pressure levels both diminished and increased relative to the axially symmetric values produced with the propeller at zero angle of attack. Attempts have been made to explain this non axially symmetric sound field based on the unsteady (once per rev) loading experienced by the propeller blades when the propeller axis is at non zero angle of attack. A calculation based on this notion appears to greatly underestimate the measured azimuthal asymmetry of noise for high tip speed, highly loaded propellers. A new mechanism is proposed; namely, that at angle of attack, there is a non axially symmetric modulation of the radiative efficiency of the steady loading and thickness noise which is the primary cause of the non axially symmetric sound field at angle of attack for high tip speed, heavily loaded propellers with a large number of blades. A calculation of this effect to first order in the crossflow Mach number (component of freestream Mach number normal to the propeller axis) is carried out and shows much better agreement with measured noise data on the angle of attack effect.

  14. Modulation of mechanical and muscular load by footwear during catering.

    PubMed

    Kersting, U G; Janshen, L; Böhm, H; Morey-Klapsing, G M; Brüggemann, G-P

    2005-03-15

    The BGN (Berufsgenossenschaft Nahrungsmithl und Gaststätten) reports 70% of job induced days off work to be connected with traumas of the ankle joint or overloading of the leg, knee and lower back, with an increased incidence in service areas outdoors (R. Grieshaber, personal communication). Workspace environments usually contain narrow passages, slopes or stairs and sudden changes between different surfaces. The aim of this study was to investigate the biomechanical load on the lower extremity and the low back during catering service when wearing different types of footwear. Thus, the potential for altering mechanical stress experienced during catering by variations in footwear was explored. Sixteen experienced waiters followed a course typical for a combined indoor-outdoor service area. Three different types of footwear were investigated using pressure distribution measurements, rearfoot goniometry and electromyography. A discriminant analysis revealed that the factors subject, shoe and surface affect rear foot movement or pressure distribution in different ways. A MANOVA demonstrated significant differences in loading parameters between footwear types. In general, these differences increased in magnitude in critical situations, such as climbing stairs or crossing slippery surfaces. The results of this study demonstrate that manipulations to footwear offer a great potential for modulating loads experienced during catering. Based on the results, the effects of constructional features are discussed. The method proposed can be applied to evaluate shoe modifications under realistic workplace conditions.

  15. Stability of mechanical joints in launching vehicles: Local and global stationary values of energy density

    NASA Astrophysics Data System (ADS)

    Chue, Ching-Hwei

    A method was developed for predicting the behavior of mechanical joints in launch vehicles with particular emphasis placed on how the combined effects of loading, geometry, and materials could be optimized in terms of structure instability and/or integrity. What was considered to be essential is the fluctuation of the volume energy density with time in the structure. The peaks and valleys of the volume energy density function will be associated with failure by fracture and/or yielding while the distance between their local and global stationary values govern the structure instability. The Solid Rocket Booster (SRB) of the space shuttle was analyzed under axisymmetric and non-axisymmetric loadings. A semi-analytical finite element program was developed for solving the case of non-axisymmetric loading. Following a dynamic stress analysis, contours of the volume energy density in the structure were obtained as a function of time. The magnitudes and locations of these stationary values were then calculated locally and globally and related to possible failure by fracture. In the case of axisymmetric flight, the local and global instability behavior do not change appreciably. Fluctuations in the energy density and the dynamic stability length parameter become appreciable when the non-axisymmetric loads are considered. The magnitude of the energy in the shell structure is sensitive to alterations in the gas pressure induced by the solid propellant.

  16. Reduced functional loads alter the physical characteristics of the bone-PDL-cementum complex

    PubMed Central

    Niver, Eric L.; Leong, Narita; Greene, Janelle; Curtis, Donald; Ryder, Mark I.; Ho, Sunita P.

    2011-01-01

    Background Adaptive properties of the bone-PDL-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed PDL-space, changes in mineral level of the cortical bone and alveolar jaw bone, and glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-PDL-cementum complex due to prolonged reduced loads has not been fully explained to date, especially with regards to concurrent adaptations of bone, PDL and cementum. Hence, the temporal effect of reduced functional loads on physical characteristics such as morphology and mechanical properties, and mineral profiles of the bone-periodontal ligament (PDL)-cementum complex using a rat model was investigated. Materials and Methods Two groups of six-week-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127–158N/mm for hard pellet or 0.32–0.47N/mm for soft powder forms. Spatio-temporal adaptation of the bone-PDL-cementum complex was identified by mapping changes in: 1) PDL-collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro X-ray computed tomography, 2) mineral profiles of the PDL-cementum and PDL-bone interfaces by X-ray attenuation, and 3) microhardness of bone and cementum by microindentation of specimens at ages six, eight, twelve, and fifteen weeks. Results Reduced functional loads over prolonged time resulted in 1) altered PDL orientation and decreased PDL collagen birefringence indicating decreased PDL turnover rate and decreased apical cementum resorption; 2) a gradual increase in X-ray attenuation, owing to mineral differences, at the PDL-bone and PDL-cementum interfaces without significant differences in the gradients for either group; 3) significantly (p<0.05) lower microhardness of alveolar bone (0.93±0.16 GPa) and secondary cementum (0.803±0.13 GPa) compared to the higher load group (1.10±0.17 GPa and 0.940±0.15 GPa respectively) at fifteen weeks indicating a temporal effect of loads on local mineralization of bone and cementum. Conclusions Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology and mechanical properties, and mineral variations and of the local load-bearing sites in a bone-PDL-cementum complex. These observed local changes in turn could help explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease, and/or orthodontic and prosthodontic treatments. PMID:21848615

  17. A clinically applicable non-invasive method to quantitatively assess the visco-hyperelastic properties of human heel pad, implications for assessing the risk of mechanical trauma.

    PubMed

    Behforootan, Sara; Chatzistergos, Panagiotis E; Chockalingam, Nachiappan; Naemi, Roozbeh

    2017-04-01

    Pathological conditions such as diabetic foot and plantar heel pain are associated with changes in the mechanical properties of plantar soft tissue. However, the causes and implications of these changes are not yet fully understood. This is mainly because accurate assessment of the mechanical properties of plantar soft tissue in the clinic remains extremely challenging. To develop a clinically viable non-invasive method of assessing the mechanical properties of the heel pad. Furthermore the effect of non-linear mechanical behaviour of the heel pad on its ability to uniformly distribute foot-ground contact loads in light of the effect of overloading is also investigated. An automated custom device for ultrasound indentation was developed along with custom algorithms for the automated subject-specific modeling of heel pad. Non-time-dependent and time-dependent material properties were inverse engineered from results from quasi-static indentation and stress relaxation test respectively. The validity of the calculated coefficients was assessed for five healthy participants. The implications of altered mechanical properties on the heel pad's ability to uniformly distribute plantar loading were also investigated in a parametric analysis. The subject-specific heel pad models with coefficients calculated based on quasi-static indentation and stress relaxation were able to accurately simulate dynamic indentation. Average error in the predicted forces for maximum deformation was only 6.6±4.0%. When the inverse engineered coefficients were used to simulate the first instance of heel strike the error in terms of peak plantar pressure was 27%. The parametric analysis indicated that the heel pad's ability to uniformly distribute plantar loads is influenced both by its overall deformability and by its stress-strain behaviour. When overall deformability stays constant, changes in stress/strain behaviour leading to a more "linear" mechanical behaviour appear to improve the heel pad's ability to uniformly distribute plantar loading. The developed technique can accurately assess the visco-hyperelastic behaviour of heel pad. It was observed that specific change in stress-strain behaviour can enhance/weaken the heel pad's ability to uniformly distribute plantar loading that will increase/decrease the risk for overloading and trauma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The Role of Peripheral Nerve Function in Age-Related Bone Loss and Changes in Bone Adaptation

    DTIC Science & Technology

    2013-10-01

    mechanical loading (months 6-18): 2a. Strain gage analysis of bone strain during tibial compression (months 6-7) 2b. Capsaicin or vehicle treatment...of neonatal mice (months 6-8) 2c. Tibial compression of capsaicin- and vehicle-injected mice (months 8-10) 2d. Micro-computed tomography of mouse...the endosteal and periosteal surfaces. Capsaicin treatment altered bone formation rate parameters in the tibias of treated mice (Table 2). There

  19. Impact of ultrasonic assisted triangular lattice like arranged dispersion of nanoparticles on physical and mechanical properties of epoxy-TiO2 nanocomposites.

    PubMed

    Goyat, M S; Ghosh, P K

    2018-04-01

    Emerging ex-situ technique, ultrasonic dual mixing (UDM) offers unique and hitherto unapproachable opportunities to alter the physical and mechanical properties of polymer nanocomposites. In this study, triangular lattice-like arranged dispersion of TiO 2 nanoparticles (average size ∼ 48 nm) in the epoxy polymer has been attained via concurrent use of a probe ultra-sonicator and 4 blades pitched impeller which collectively named as UDM technique. The UDM processing of neat epoxy reveals the generation of triangular lattice-like arranged nanocavities with nanoscale inter-cavity spacing. The UDM processing of epoxy-TiO 2 nanocomposites reveals two unique features such as partial and complete entrapping of the nanoparticles by the nanocavities leading the arranged dispersion of particles in the epoxy matrix. Pristine TiO 2 nanoparticles were dispersed in the epoxy polymer at loading fractions of up to 20% by weight. The results display that the arranged dispersion of nanoparticles is very effective at enhancing the glass transition temperature (T g ) and tensile properties of the epoxy at loading fractions of 10 wt%. We quantify a direct relationship among three important parameters such as nanoparticle content, cluster size, and inter-particle spacing. Our results offer a novel understanding of these parameters on the T g and tensile properties of the epoxy nanocomposites. The tensile fracture surfaces revealed several toughening mechanisms such as particle pull-out, plastic void growth, crack deflection, crack bridging and plastic deformation. We show that a strong nanoparticle-matrix interface led to the enhanced mechanical properties due to leading toughening mechanisms such as crack deflection, plastic deformation and particle pull-out. We showed that the UDM has an inordinate prospective to alter the dispersion state of nanoparticles in viscous polymer matrices. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Evaluating bone quality in patients with chronic kidney disease

    PubMed Central

    Malluche, Hartmut H.; Porter, Daniel S.; Pienkowski, David

    2013-01-01

    Bone of normal quality and quantity can successfully endure physiologically imposed mechanical loads. Chronic kidney disease–mineral and bone disorder (CKD–MBD) adversely affects bone quality through alterations in bone turnover and mineralization, whereas bone quantity is affected through changes in bone volume. Changes in bone quality can be associated with altered bone material, structure, or microdamage, which can result in an elevated rate of fracture in patients with CKD–MBD. Fractures cannot always be explained by reduced bone quantity and, therefore, bone quality should be assessed with a variety of techniques from the macro-organ level to the nanoscale level. In this Review, we demonstrate the importance of evaluating bone from multiple perspectives and hierarchical levels to understand CKD–MBD-related abnormalities in bone quality. Understanding the relationships between variations in material, structure, microdamage, and mechanical properties of bone in patients with CKD–MBD should aid in the development of new modalities to prevent, or treat, these abnormalities. PMID:24100399

  1. Mechanism of hyperinsulinemia after reticuloendothelial system phagocytosis.

    PubMed

    Filkins, J P; Yelich, M R

    1982-02-01

    Endocytic loading of the reticuloendothelial system (RES) results in acute hyperinsulinemia and functional hyperinsulinism. Colloidal carbon blockade of the RES in rats resulted in elevations of both portal vein and systemic serum immunoreactive insulin and increases in the hepatic portal vein insulin glucose ratios. Two mechanisms for the hyperinsulinemia were evaluated: 1) decreased removal of insulin by the postendocytic liver and 2) increased secretion of insulin by the isolated perfused pancreas. Colloidal carbon blockade did not alter removal of 125I-insulin as evaluated in the isolated perfused rat liver. Pancreases from postendocytic donor rats when perfused according to the technique of Grodsky manifested enhanced insulin secretion. Macrophage culture-conditioned media enhanced glucose-mediated insulin secretion both as assayed in vivo and in the isolated perfused rat pancreas. The data suggest that postendocytic activated macrophages secrete a monokine that alters insulin release and thus produces the hyperinsulinemia of RES blockade. The acronym MIRA for macrophage insulin-releasing activity is proposed for the monokine.

  2. Use of a backpack alters gait initiation of high school students.

    PubMed

    Vieira, Marcus Fraga; Lehnen, Georgia Cristina; Noll, Matias; Rodrigues, Fábio Barbosa; de Avelar, Ivan Silveira; da Costa, Paula Hentschel Lobo

    2016-06-01

    We assessed how backpack carriage influences the gait initiation (GI) process in high school students, who extensively use backpacks. GI involves different dynamics from gait itself, while the excessive use of backpacks can result in adverse effects. 117 high school students were evaluated in three experimental conditions: no backpack (NB), bilateral backpack (BB), and unilateral backpack (UB). Two force plates were used to acquire ground reaction forces (GRFs) and moments for each foot separately. Center of pressure (COP) scalar variables were extracted, and statistical parametric mapping analysis was performed over the entire COP/GRFs time series. GI anticipatory postural adjustments (APAs) were reduced and were faster in backpack conditions; medial-lateral COP excursion was smaller in this phase. The uneven distribution of the extra load in the UB condition led to a larger medial-lateral COP shift in the support-foot unloading phase, with a corresponding vertical GRF change that suggests a more pronounced unloading swing foot/loading support foot mechanism. The anterior-posterior GRFs were altered, but the COP was not. A possible explanation for these results may be the forward trunk lean and the center of mass proximity of the base of support boundary, which induced smaller and faster APA, increased swing foot/support foot weight transfer, and increased load transfer to the first step. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Measuring Regional Changes in Damaged Tendon

    NASA Astrophysics Data System (ADS)

    Frisch, Catherine Kayt Vincent

    Mechanical properties of tendon predict tendon health and function, but measuring these properties in vivo is difficult. An ultrasound-based (US) analysis technique called acoustoelastography (AE) uses load-dependent changes in the reflected US signal to estimate tissue stiffness non-invasively. This thesis explores whether AE can provide information about stiffness alteration resulting from tendon tears both ex vivo and in vivo. An ex vivo ovine infraspinatus tendon model suggests that the relative load transmitted by the different tendon layers transmit different fractions of the load and that ultrasound echo intensity change during cyclic loading decreases, becoming less consistent once the tendon is torn. An in vivo human tibialis anterior tendon model using electrically stimulated twitch contractions investigated the feasibility of measuring the effect in vivo. Four of the five subjects showed the expected change and that the muscle contraction times calculated using the average grayscale echo intensity change compared favorably with the times calculated based on the force data. Finally an AE pilot study with patients who had rotator cuff tendon tears found that controlling the applied load and the US view of the system will be crucial to a successful in vivo study.

  4. Patellofemoral Joint Loads During Running at the Time of Return to Sport in Elite Athletes With ACL Reconstruction.

    PubMed

    Herrington, Lee; Alarifi, Saud; Jones, Richard

    2017-10-01

    Patellofemoral joint pain and degeneration are common in patients who undergo anterior cruciate ligament reconstruction (ACLR). The presence of patellofemoral joint pain significantly affects the patient's ability to continue sport participation and may even affect participation in activities of daily living. The mechanisms behind patellofemoral joint pain and degeneration are unclear, but previous research has identified altered patellofemoral joint loading in individuals with patellofemoral joint pain when running. It is unclear whether this process occurs after ACLR. To assess the patellofemoral joint stresses during running in ACLR knees and compare the findings to the noninjured knee and matched control knees. Controlled laboratory study. Thirty-four elite sports practitioners who had undergone ACLR and 34 age- and sex-matched controls participated in the study. The participants' running gait was assessed via 3D motion capture, and knee loads and forces were calculated by use of inverse dynamics. A significance difference was found in knee extensor moment, knee flexion angles, patellofemoral contact force (about 23% greater), and patellofemoral contact pressure (about 27% greater) between the ACLR and the noninjured limb ( P ≤ .04) and between the ACLR and the control limb ( P ≤ .04); no significant differences were found between the noninjured and control limbs ( P ≥ .44). Significantly greater levels of patellofemoral joint stress and load were found in the ACLR knee compared with the noninjured and control knees. Altered levels of patellofemoral stress in the ACLR knee during running may predispose individuals to patellofemoral joint pain.

  5. Bioinspired Technologies to Connect Musculoskeletal Mechanobiology to the Person for Training and Rehabilitation

    PubMed Central

    Pizzolato, Claudio; Lloyd, David G.; Barrett, Rod S.; Cook, Jill L.; Zheng, Ming H.; Besier, Thor F.; Saxby, David J.

    2017-01-01

    Musculoskeletal tissues respond to optimal mechanical signals (e.g., strains) through anabolic adaptations, while mechanical signals above and below optimal levels cause tissue catabolism. If an individual's physical behavior could be altered to generate optimal mechanical signaling to musculoskeletal tissues, then targeted strengthening and/or repair would be possible. We propose new bioinspired technologies to provide real-time biofeedback of relevant mechanical signals to guide training and rehabilitation. In this review we provide a description of how wearable devices may be used in conjunction with computational rigid-body and continuum models of musculoskeletal tissues to produce real-time estimates of localized tissue stresses and strains. It is proposed that these bioinspired technologies will facilitate a new approach to physical training that promotes tissue strengthening and/or repair through optimal tissue loading. PMID:29093676

  6. Measurement of red blood cell mechanics during morphological changes

    PubMed Central

    Park, YongKeun; Best, Catherine A.; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.; Kuriabova, Tatiana; Henle, Mark L.; Levine, Alex J.; Popescu, Gabriel

    2010-01-01

    The human red blood cell (RBC) membrane, a fluid lipid bilayer tethered to an elastic 2D spectrin network, provides the principal control of the cell’s morphology and mechanics. These properties, in turn, influence the ability of RBCs to transport oxygen in circulation. Current mechanical measurements of RBCs rely on external loads. Here we apply a noncontact optical interferometric technique to quantify the thermal fluctuations of RBC membranes with 3 nm accuracy over a broad range of spatial and temporal frequencies. Combining this technique with a new mathematical model describing RBC membrane undulations, we measure the mechanical changes of RBCs as they undergo a transition from the normal discoid shape to the abnormal echinocyte and spherical shapes. These measurements indicate that, coincident with this morphological transition, there is a significant increase in the membrane’s shear, area, and bending moduli. This mechanical transition can alter cell circulation and impede oxygen delivery. PMID:20351261

  7. Osteoarthritis year in review 2015: mechanics.

    PubMed

    Varady, N H; Grodzinsky, A J

    2016-01-01

    Motivated by the conceptual framework of multi-scale biomechanics, this narrative review highlights recent major advances with a focus on gait and joint kinematics, then tissue-level mechanics, cell mechanics and mechanotransduction, matrix mechanics, and finally the nanoscale mechanics of matrix macromolecules. A literature review was conducted from January 2014 to April 2015 using PubMed to identify major developments in mechanics related to osteoarthritis (OA). Studies of knee adduction, flexion, rotation, and contact mechanics have extended our understanding of medial compartment loading. In turn, advances in measurement methodologies have shown how injuries to both the meniscus and ligaments, together, can alter joint kinematics. At the tissue scale, novel findings have emerged regarding the mechanics of the meniscus as well as cartilage superficial zone. Moving to the cell level, poroelastic and poro-viscoelastic mechanisms underlying chondrocyte deformation have been reported, along with the response to osmotic stress. Further developments have emerged on the role of calcium signaling in chondrocyte mechanobiology, including exciting findings on the function of mechanically activated cation channels newly found to be expressed in chondrocytes. Finally, AFM-based nano-rheology systems have enabled studies of thin murine tissues and brush layers of matrix molecules over a wide range of loading rates including high rates corresponding to impact injury. With OA acknowledged to be a disease of the joint as an organ, understanding mechanical behavior at each length scale helps to elucidate the connections between cell biology, matrix biochemistry and tissue structure/function that may play a role in the pathomechanics of OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  8. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    NASA Technical Reports Server (NTRS)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  9. Tensegrity and mechanoregulation: from skeleton to cytoskeleton

    NASA Technical Reports Server (NTRS)

    Chen, C. S.; Ingber, D. E.

    1999-01-01

    OBJECTIVE: To elucidate how mechanical stresses that are applied to the whole organism are transmitted to individual cells and transduced into a biochemical response. DESIGN: In this article, we describe fundamental design principles that are used to stabilize the musculoskeletal system at many different size scales and show that these design features are embodied in one particular form of architecture that is known as tensegrity. RESULTS: Tensegrity structures are characterized by use of continuous tension and local compression; architecture, prestress (internal stress prior to application of external force), and triangulation play the most critical roles in terms of determining their mechanical stability. In living organisms, use of a hierarchy of tensegrity networks both optimizes structural efficiency and provides a mechanism to mechanically couple the parts with the whole: mechanical stresses applied at the macroscale result in structural rearrangements at the cell and molecular level. CONCLUSION: Due to use of tensegrity architecture, mechanical stress is concentrated and focused on signal transducing molecules that physically associate with cell surface molecules that anchor cells to extracellular matrix, such as integrins, and with load-bearing elements within the internal cytoskeleton and nucleus. Mechanochemical transduction may then proceed through local stress-dependent changes in molecular mechanics, thermodynamics, and kinetics within the cell. In this manner, the entire cellular response to stress may be orchestrated and tuned by altering the prestress in the cell, just as changing muscular tone can alter mechanical stability and structural coordination throughout the whole musculoskeletal system.

  10. A Bioreactor to Identify the Driving Mechanical Stimuli of Tissue Growth and Remodeling.

    PubMed

    van Kelle, Mathieu A J; Oomen, Pim J A; Bulsink, Jurgen A; Janssen-van den Broek, Marloes W J T; Lopata, Richard G P; Rutten, Marcel C M; Loerakker, Sandra; Bouten, Carlijn V C

    2017-06-01

    Tissue growth and remodeling are essential processes that should ensure long-term functionality of tissue-engineered (TE) constructs. Even though it is widely recognized that these processes strongly depend on mechanical stimuli, the underlying mechanisms of mechanically induced growth and remodeling are only partially understood. It is generally accepted that cells sense mechanical changes and respond by altering their surroundings, by means of extracellular matrix growth and remodeling, in an attempt to return to a certain preferred mechanical homeostatic state. However, the exact mechanical cues that trigger cells to synthesize and remodel their environment remain unclear. To identify the driving mechanical stimuli of these processes, it is critical to be able to temporarily follow the mechanical state of developing tissues under physiological loading conditions. Therefore, a novel "versatile tissue growth and remodeling" (Vertigro) bioreactor was developed that is capable of tissue culture and mechanical stimulation for a prolonged time period, while simultaneously performing mechanical testing. The Vertigro's unique two-chamber design allows easy, sterile handling of circular 3D TE constructs in a dedicated culture chamber, while a separate pressure chamber facilitates a pressure-driven dynamic loading regime during culture. As a proof-of-concept, temporal changes in the mechanical state of cultured tissues were quantified using nondestructive mechanical testing by means of a classical bulge test, in which the tissue displacement was tracked using ultrasound imaging. To demonstrate the successful development of the bioreactor system, compositional, structural, and geometrical changes were qualitatively and quantitatively assessed using a series of standard analysis techniques. With this bioreactor and associated mechanical analysis technique, a powerful toolbox has been developed to quantitatively study and identify the driving mechanical stimuli of engineered tissue growth and remodeling.

  11. Inhibition of Staphylococcus epidermidis biofilms using polymerizable vancomycin derivatives.

    PubMed

    Lawson, McKinley C; Hoth, Kevin C; Deforest, Cole A; Bowman, Christopher N; Anseth, Kristi S

    2010-08-01

    Biofilm formation on indwelling medical devices is a ubiquitous problem causing considerable patient morbidity and mortality. In orthopaedic surgery, this problem is exacerbated by the large number and variety of material types that are implanted. Metallic hardware in conjunction with polymethylmethacrylate (PMMA) bone cement is commonly used. We asked whether polymerizable derivatives of vancomycin might be useful to (1) surface modify Ti-6Al-4V alloy and to surface/bulk modify PMMA bone cement to prevent Staphylococcus epidermidis biofilm formation and (2) whether the process altered the compressive modulus, yield strength, resilience, and/or fracture strength of cement copolymers. A Ti-6Al-4V alloy was silanized with methacryloxypropyltrimethoxysilane in preparation for subsequent polymer attachment. Surfaces were then coated with polymers formed from PEG(375)-acrylate or a vancomycin-PEG(3400)-PEG(375)-acrylate copolymer. PMMA was loaded with various species, including vancomycin and several polymerizable vancomycin derivatives. To assess antibiofilm properties of these materials, initial bacterial adherence to coated Ti-6Al-4V was determined by scanning electron microscopy (SEM). Biofilm dry mass was determined on PMMA coupons; the compressive mechanical properties were also determined. SEM showed the vancomycin-PEG(3400)-acrylate-type surface reduced adherent bacteria numbers by approximately fourfold when compared with PEG(375)-acrylate alone. Vancomycin-loading reduced all mechanical properties tested; in contrast, loading a vancomycin-acrylamide derivative restored these deficits but demonstrated no antibiofilm properties. A polymerizable, PEGylated vancomycin derivative reduced biofilm attachment but resulted in inferior cement mechanical properties. The approaches presented here may offer new strategies for developing biofilm-resistant orthopaedic materials. Specifically, polymerizable derivatives of traditional antibiotics may allow for direct polymerization into existing materials such as PMMA bone cement while minimizing mechanical property compromise. Questions remain regarding ideal monomer structure(s) that confer biologic and mechanical benefits.

  12. The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis

    PubMed Central

    Anderson, Donald D.; Brown, Thomas D.; Tochigi, Yuki; Martin, James A.

    2013-01-01

    Excessive joint surface loadings, either single (acute impact event) or repetitive (cumulative contact stress), can cause the clinical syndrome of osteoarthritis (OA). Despite advances in treatment of injured joints, the risk of OA following joint injuries has not decreased in the past 50 years. Cumulative excessive articular surface contact stress that leads to OA results from posttraumatic joint incongruity and instability, and joint dysplasia, but may also cause OA in patients without known joint abnormalities. In vitro investigations show that excessive articular cartilage loading triggers release of reactive oxygen species (ROS) from mitochondria, and that these ROS cause chondrocyte death and matrix degradation. Preventing release of ROS or inhibiting their effects preserves chondrocytes and their matrix. Fibronectin fragments released from articular cartilage subjected to excessive loads also stimulate matrix degradation; inhibition of molecular pathways initiated by these fragments prevents this effect. Additionally, injured chondrocytes release alarmins that activate chondroprogentior cells in vitro that propogate and migrate to regions of damaged cartilage. These cells also release chemokines and cytokines that may contribute to inflammation that causes progressive cartilage loss. Distraction and motion of osteoarthritic human ankles can promote joint remodeling, decrease pain, and improve joint function in patients with end-stage posttraumatic OA. These advances in understanding of how altering mechanical stresses can lead to remodeling of osteoarthritic joints and how excessive stress causes loss of articular cartilage, including identification of mechanically induced mediators of cartilage loss, provide the basis for new biologic and mechanical approaches to the prevention and treatment of OA. PMID:25067995

  13. Left ventricular torsional mechanics and myocardial iron load in beta-thalassaemia major: a potential role of titin degradation.

    PubMed

    Chen, Mei-Pian; Li, Shu-Na; Lam, Wendy W M; Ho, Yuen-Chi; Ha, Shau-Yin; Chan, Godfrey C F; Cheung, Yiu-Fai

    2014-04-12

    Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin. In 44 thalassaemia patients aged 25 ± 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.

  14. Effects of Inflammation on Multiscale Biomechanical Properties of Cartilaginous Cells and Tissues

    PubMed Central

    2017-01-01

    Cells within cartilaginous tissues are mechanosensitive and thus require mechanical loading for regulation of tissue homeostasis and metabolism. Mechanical loading plays critical roles in cell differentiation, proliferation, biosynthesis, and homeostasis. Inflammation is an important event occurring during multiple processes, such as aging, injury, and disease. Inflammation has significant effects on biological processes as well as mechanical function of cells and tissues. These effects are highly dependent on cell/tissue type, timing, and magnitude. In this review, we summarize key findings pertaining to effects of inflammation on multiscale mechanical properties at subcellular, cellular, and tissue level in cartilaginous tissues, including alterations in mechanotransduction and mechanosensitivity. The emphasis is on articular cartilage and the intervertebral disc, which are impacted by inflammatory insults during degenerative conditions such as osteoarthritis, joint pain, and back pain. To recapitulate the pro-inflammatory cascades that occur in vivo, different inflammatory stimuli have been used for in vitro and in situ studies, including tumor necrosis factor (TNF), various interleukins (IL), and lipopolysaccharide (LPS). Therefore, this review will focus on the effects of these stimuli because they are the best studied pro-inflammatory cytokines in cartilaginous tissues. Understanding the current state of the field of inflammation and cell/tissue biomechanics may potentially identify future directions for novel and translational therapeutics with multiscale biomechanical considerations. PMID:29152560

  15. Effects of Inflammation on Multiscale Biomechanical Properties of Cartilaginous Cells and Tissues.

    PubMed

    Nguyen, Q T; Jacobsen, T D; Chahine, N O

    2017-11-13

    Cells within cartilaginous tissues are mechanosensitive and thus require mechanical loading for regulation of tissue homeostasis and metabolism. Mechanical loading plays critical roles in cell differentiation, proliferation, biosynthesis, and homeostasis. Inflammation is an important event occurring during multiple processes, such as aging, injury, and disease. Inflammation has significant effects on biological processes as well as mechanical function of cells and tissues. These effects are highly dependent on cell/tissue type, timing, and magnitude. In this review, we summarize key findings pertaining to effects of inflammation on multiscale mechanical properties at subcellular, cellular, and tissue level in cartilaginous tissues, including alterations in mechanotransduction and mechanosensitivity. The emphasis is on articular cartilage and the intervertebral disc, which are impacted by inflammatory insults during degenerative conditions such as osteoarthritis, joint pain, and back pain. To recapitulate the pro-inflammatory cascades that occur in vivo, different inflammatory stimuli have been used for in vitro and in situ studies, including tumor necrosis factor (TNF), various interleukins (IL), and lipopolysaccharide (LPS). Therefore, this review will focus on the effects of these stimuli because they are the best studied pro-inflammatory cytokines in cartilaginous tissues. Understanding the current state of the field of inflammation and cell/tissue biomechanics may potentially identify future directions for novel and translational therapeutics with multiscale biomechanical considerations.

  16. Characterization of craniofacial sutures using the finite element method.

    PubMed

    Maloul, Asmaa; Fialkov, Jeffrey; Wagner, Diane; Whyne, Cari M

    2014-01-03

    Characterizing the biomechanical behavior of sutures in the human craniofacial skeleton (CFS) is essential to understand the global impact of these articulations on load transmission, but is challenging due to the complexity of their interdigitated morphology, the multidirectional loading they are exposed to and the lack of well-defined suture material properties. This study aimed to quantify the impact of morphological features, direction of loading and suture material properties on the mechanical behavior of sutures and surrounding bone in the CFS. Thirty-six idealized finite element (FE) models were developed. One additional specimen-specific FE model was developed based on the morphology obtained from a µCT scan to represent the morphological complexity inherent in CFS sutures. Outcome variables of strain energy (SE) and von Mises stress (σvm) were evaluated to characterize the sutures' biomechanical behavior. Loading direction was found to impact the relationship between SE and interdigitation index and yielded varied patterns of σvm in both the suture and surrounding bone. Adding bone connectivity reduced suture strain energy and altered the σvm distribution. Incorporating transversely isotropic material properties was found to reduce SE, but had little impact on stress patterns. High-resolution µCT scanning of the suture revealed a complex morphology with areas of high and low interdigitations. The specimen specific suture model results were reflective of SE absorption and σvm distribution patterns consistent with the simplified FE results. Suture mechanical behavior is impacted by morphologic factors (interdigitation and connectivity), which may be optimized for regional loading within the CFS. © 2013 Elsevier Ltd. All rights reserved.

  17. Manipulation of sarcoplasmic reticulum Ca2+ release in heart failure through mechanical intervention

    PubMed Central

    Ibrahim, Michael; Nader, Anas; Yacoub, Magdi H; Terracciano, Cesare

    2015-01-01

    Left ventricular assist devices (LVADs) were developed as a means of temporary circulatory support, but the mechanical unloading they offer also results in significant reverse remodelling. In selected patients, these improvements are sufficient to allow ultimate device explantation without requiring transplantation; this represents a fundamental shift in our understanding of heart failure. Like heart failure itself, LVADs influence multiple biological systems. The transverse tubules are a system of membrane invaginations in ventricular cardiomyocytes which allow rapid propagation of the action potential throughout the cell. Through their dense concentration of L-type Ca2+ channels in close proximity to intracellular ryanodine receptors, the t-tubules enable synchronous Ca2+ release throughout the cell. The t-tubules’ structure appears to be specifically regulated by mechanical load, such that either the overload of heart failure (or the spontaneously hypertensive rat model) or the profound unloading in a chronically unloaded heart result in impaired t-tubule structure, with ineffective Ca2+ release. While there are multiple molecular pathways which underpin t-tubule regulation, Telethonin (Tcap) appears to be important in regulating the effect of altered loading on the t-tubule system. PMID:25922157

  18. Effects of cyclic hydraulic pressure on osteocytes.

    PubMed

    Liu, Chao; Zhao, Yan; Cheung, Wing-Yee; Gandhi, Ronak; Wang, Liyun; You, Lidan

    2010-05-01

    Bone is able to adapt its composition and structure in order to suit its mechanical environment. Osteocytes, bone cells embedded in the calcified matrix, are believed to be the mechanosensors and responsible for orchestrating the bone remodeling process. Recent in vitro studies have shown that osteocytes are able to sense and respond to substrate strain and fluid shear. However the capacity of osteocytes to sense cyclic hydraulic pressure (CHP) associated with physiological mechanical loading is not well understood. In this study, we subjected osteocyte-like MLO-Y4 cells to controlled CHP of 68 kPa at 0.5 Hz, and investigated the effects of CHP on intracellular calcium concentration, cytoskeleton organization, mRNA expression of genes related to bone remodeling, and osteocyte apoptosis. We found that osteocytes were able to sense CHP and respond by increased intracellular calcium concentration, altered microtubule organization, a time-dependent increase in COX-2 mRNA level and RANKL/OPG mRNA ratio, and decreased apoptosis. These findings support the hypothesis that loading induced cyclic hydraulic pressure in bone serves as a mechanical stimulus to osteocytes and may play a role in regulating bone remodeling in vivo. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  19. Alteration of functional loads after tongue volume reduction.

    PubMed

    Ye, W; Duan, Y Z; Liu, Z J

    2013-11-01

    An earlier study revealed that the patterns of biomechanical loads on bones around the tongue altered significantly right after tongue volume reduction surgery. The current study was to examine whether these alterations persist or vanish over time post-surgery. Five sibling pairs of 12-week-old Yucatan minipigs were used. For each pair, one had surgery reducing tongue volume by about 15% (reduction) while the other had same incisions without tissue removal (sham). All animals were raised for 4 weeks after surgery. Three rosette strain gauges were placed on the bone surfaces of pre-maxilla (PM), mandibular incisor (MI), and mandibular molar (MM); two single-element gauges were placed across the pre-maxilla-maxillar suture (PMS) and mandibular symphysis (MSP), and two pressure transducers were placed on the bone surfaces of hard palate (PAL) and mandibular body (MAN). These bone strains and pressures were recorded during natural mastication. Overall amount of all loads increased significantly as compared to those in previous study in all animals. Instead of decreased loads in reduction animals as seen in that study, shear strains at PM, MI, and MM, tensile strains at PMS, and pressure at MAN were significantly higher in reduction than sham animals. Compared to the sham, strain dominance shifted at PM, MI, and MM and orientation of tensile strain altered at MI in reduction animals. A healed volume-reduced tongue may change loading regime significantly by elevating loading and altering strain-dominant pattern and orientation on its surrounding structures, and these changes are more remarkable in mandibular than maxillary sites. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function.

    PubMed

    Wang, Vicky Y; Lam, H I; Ennis, Daniel B; Cowan, Brett R; Young, Alistair A; Nash, Martyn P

    2009-10-01

    The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

  1. Monitoring Damage Propagation in Glass Fiber Composites Using Carbon Nanofibers.

    PubMed

    Al-Sabagh, Ahmed; Taha, Eman; Kandil, Usama; Nasr, Gamal-Abdelnaser; Reda Taha, Mahmoud

    2016-09-10

    In this work, we report the potential use of novel carbon nanofibers (CNFs), dispersed during fabrication of glass fiber composites to monitor damage propagation under static loading. The use of CNFs enables a transformation of the typically non-conductive glass fiber composites into new fiber composites with appreciable electrical conductivity. The percolation limit of CNFs/epoxy nanocomposites was first quantified. The electromechanical responses of glass fiber composites fabricated using CNFs/epoxy nanocomposite were examined under static tension loads. The experimental observations showed a nonlinear change of electrical conductivity of glass fiber composites incorporating CNFs versus the stress level under static load. Microstructural investigations proved the ability of CNFs to alter the polymer matrix and to produce a new polymer nanocomposite with a connected nanofiber network with improved electrical properties and different mechanical properties compared with the neat epoxy. It is concluded that incorporating CNFs during fabrication of glass fiber composites can provide an innovative means of self-sensing that will allow damage propagation to be monitored in glass fiber composites.

  2. Characterization of Impact Damage in Ultra-High Performance Concrete Using Spatially Correlated Nanoindentation/SEM/EDX

    NASA Astrophysics Data System (ADS)

    Moser, R. D.; Allison, P. G.; Chandler, M. Q.

    2013-12-01

    Little work has been done to study the fundamental material behaviors and failure mechanisms of cement-based materials including ordinary Portland cement concrete and ultra-high performance concretes (UHPCs) under high strain impact and penetration loads at lower length scales. These high strain rate loadings have many possible effects on UHPCs at the microscale and nanoscale, including alterations in the hydration state and bonding present in phases such as calcium silicate hydrate, in addition to fracture and debonding. In this work, the possible chemical and physical changes in UHPCs subjected to high strain rate impact and penetration loads were investigated using a novel technique wherein nanoindentation measurements were spatially correlated with images using scanning electron microscopy and chemical composition using energy dispersive x-ray microanalysis. Results indicate that impact degrades both the elastic modulus and indentation hardness of UHPCs, and in particular hydrated phases, with damage likely occurring due to microfracturing and debonding.

  3. Dietary variation and mechanical properties of articular cartilage in the temporomandibular joint: implications for the role of plasticity in mechanobiology and pathobiology.

    PubMed

    Ravosa, Matthew J; Kane, Robert J

    2017-10-01

    Due to their nature as tissue composites, skeletal joints pose an additional challenge in terms of evaluating the functional significance of morphological variation in their bony and cartilaginous components in response to altered loading conditions. Arguably, this complexity requires more direct means of investigating joint plasticity and performance than typically employed to analyze macro- and micro-anatomical phenomena. To address a significant gap in our understanding of the plasticity of the mammalian temporomandibular joint (TMJ), we investigated the histology and mechanical properties of condylar articular cartilage in rabbits subjected to long-term variation in diet-induced masticatory stresses, specifically cyclical loading. Three cohorts of male weanlings were raised for six months on different diets until adulthood. Following euthanasia, the TMJ condyles on one side were dissected away, fixed, decalcified, dehydrated, embedded and sectioned. Safranin O staining was employed to identify variation in proteoglycan content, which in turn was used to predict patterns of articular cartilage stiffness in contralateral condylar specimens for each treatment group. Hematoxylin and eosin staining was used to quantify diet-induced changes in chondrocyte hypertrophy and cellularity. Mechanical tests document significant decreases in articular cartilage stiffness corresponding to patterns of extracellular matrix relative protein abundance in rabbits subjected to greater cyclical loading. This indicates that TMJs routinely subjected to higher masticatory stresses due to a challenging diet eventually develop postnatal decreases in the ability to counter compressive loads during postcanine biting and chewing. These findings provide novel information regarding TMJ performance, with broader implications about the costs and benefits of phenotypic plasticity as well as implications for how such biological processes affect connective tissue mechanobiology and pathobiology. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. PHOSPHO1 is essential for mechanically competent mineralization and the avoidance of spontaneous fractures

    PubMed Central

    Huesa, Carmen; Yadav, Manisha C.; Finnilä, Mikko A.J.; Goodyear, Simon R.; Robins, Simon P.; Tanner, K. Elizabeth; Aspden, Richard M.; Millán, José Luis; Farquharson, Colin

    2011-01-01

    Phosphatases are essential for the mineralization of the extracellular matrix within the skeleton. Their precise identities and functions however remain unclear. PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase involved in the generation of inorganic phosphate for bone mineralization. It is highly expressed at sites of mineralization in bone and cartilage. The bones of Phospho1−/− mice are hypomineralized, bowed and present with spontaneous greenstick fractures at birth. In this study we show that PHOSPHO1 is essential for mechanically competent mineralization that is able to withstand habitual load. Long bones from Phospho1−/− mice did not fracture during 3- point bending but deformed plastically. With dynamic loading nanoindentation the elastic modulus and hardness of Phospho1−/− tibiae were significantly lower than wild-type tibia. Raman microscopy revealed significantly lower mineral:matrix ratios and lower carbonate substitutions in Phospho1−/− tibia. The altered dihydroxylysinonorleucine/hydroxyllysinonorleucine and pyridoline/deoxypyridinoline collagen crosslink ratios indicated possible changes in lysyl hydroxylase-1 activity and/or bone mineralization status. The bone formation and resorption markers, N-terminal propeptide and C-terminal telopeptide of Type I collagen, were both increased in Phospho1−/− mice and this we associated with increased bone remodelling during fracture repair or an attempt to remodel a mechanically competent bone capable of withstanding physiological load. In summary these data indicate that Phospho1−/− bones are hypomineralized and, consequently, are softer and more flexible. An inability to withstand physiological loading may explain the deformations noted. We hypothesize that this phenotype is due to the reduced availability of inorganic phosphate to form hydroxyapatite during mineralization, creating an undermineralized yet active bone. PMID:21272676

  5. Differences in knee joint kinematics and forces after posterior cruciate retaining and stabilized total knee arthroplasty.

    PubMed

    Wünschel, Markus; Leasure, Jeremi M; Dalheimer, Philipp; Kraft, Nicole; Wülker, Nikolaus; Müller, Otto

    2013-12-01

    Posterior cruciate ligament (PCL) retaining (CR) and -sacrificing (PS) total knee arthroplasties (TKA) are widely-used to treat osteoarthritis of the knee joint. The PS design substitutes the function of the PCL with a cam-spine mechanism which may produce adverse changes to joint kinematics and kinetics. CR- and PS-TKA were performed on 11 human knee specimens. Joint kinematics were measured with a dynamic knee simulator and motion tracking equipment. In-situ loads of the PCL and cam-spine were measured with a robotic force sensor system. Partial weight bearing flexions were simulated and external forces were applied. The PS-TKA rotated significantly less throughout the whole flexion range compared to the CR-TKA. Femoral roll back was greater in the PS-TKA; however, this was not correlated with lower quadriceps forces. Application of external loads produced significantly different in-situ force profiles between the TKA systems. Our data demonstrate that the PS-design significantly alters kinematics of the knee joint. Our data also suggest the cam-spine mechanism may have little influence on high flexion kinematics (such as femoral rollback) with most of the load burden shared by supporting implant and soft-tissue structures. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint

    PubMed Central

    Rai, Muhammad Farooq; Duan, Xin; Quirk, James D.; Holguin, Nilsson; Schmidt, Eric J.; Chinzei, Nobuaki; Silva, Matthew J.; Sandell, Linda J.

    2017-01-01

    We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention. PMID:28345597

  7. Textile properties of synthetic prolapse mesh in response to uniaxial loading.

    PubMed

    Barone, William R; Moalli, Pamela A; Abramowitch, Steven D

    2016-09-01

    Although synthetic mesh is associated with superior anatomic outcomes for the repair of pelvic organ prolapse, the benefits of mesh have been questioned because of the relatively high complication rates. To date, the mechanisms that result in such complications are poorly understood, yet the textile characteristics of mesh products are believed to play an important role. Interestingly, the pore diameter of synthetic mesh has been shown to impact the host response after hernia repair greatly, and such findings have served as design criteria for prolapse meshes, with larger pores viewed as more favorable. Although pore size and porosity are well-characterized before implantation, the changes in these textile properties after implantation are unclear; the application of mechanical forces has the potential to greatly alter pore geometries in vivo. Understanding the impact of mechanical loading on the textile properties of mesh is essential for the development of more effective devices for prolapse repair. The objective of this study was to determine the effect of tensile loading and pore orientation on mesh porosity and pore dimensions. In this study, the porosity and pore diameter of 4 currently available prolapse meshes were examined in response to uniaxial tensile loads of 0.1, 5, and 10 N while mimicking clinical loading conditions. The textile properties were compared with those observed for the unloaded mesh. Meshes included Gynemesh PS (Ethicon, Somerville, NJ), UltraPro (Artisyn; Ethicon), Restorelle (Coloplast, Minneapolis, MN), and Alyte Y-mesh (Bard, Covington, GA). In addition to the various pore geometries, 3 orientations of Restorelle (0-, 5-, 45-degree offset) and 2 orientations of UltraPro (0-, 90-degree offset) were examined. In response to uniaxial loading, both porosity and pore diameter dramatically decreased for most mesh products. The application of 5 N led to reductions in porosity for nearly all groups, with values decreasing by as much as 87% (P < .05). On loading to 10 N of force, nearly all mesh products that were tested were found to have porosities that approached 0% and 0 pores with diameters >1 mm. In this study, it was shown that the pore size of current prolapse meshes dramatically decreases in response to mechanical loading. These findings suggest that prolapse meshes, which are more likely to experience tensile forces in vivo relative to hernia repair meshes, have pores that are unfavorable for tissue integration after surgical tensioning and/or loading in urogynecologic surgeries. Such decreases in pore geometry support the hypothesis that regional increases in the concentration of mesh leads to an enhanced local foreign body response. Although pore deformation in transvaginal meshes requires further characterization, the findings presented here provide a mechanical understanding that can be used to recognize potential areas of concern for complex mesh geometries. Understanding mesh mechanics in response to surgical and in vivo loading conditions may provide improved design criteria for mesh and a refinement of surgical techniques, ultimately leading to better patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Fuel loadings in forests, woodlands, and savannas of the Madrean province

    Treesearch

    Peter F. Ffolliott; Gerald J. Gottfried; Leonard F. DeBano

    2008-01-01

    Natural fire regimes in the southwestern United States have been significantly altered by past land-use practices and the fire suppression polices of land management agencies. One consequence of this alteration has been to increase the loadings of downed woody fuels. Ecologists and land managers are reintroducing fire into the ecosystems of the Madrean Province to...

  9. Long-term load duration induces N-cadherin down-regulation and loss of cell phenotype of nucleus pulposus cells in a disc bioreactor culture.

    PubMed

    Li, Pei; Zhang, Ruijie; Wang, Liyuan; Gan, Yibo; Xu, Yuan; Song, Lei; Luo, Lei; Zhao, Chen; Zhang, Chengmin; Ouyang, Bin; Tu, Bing; Zhou, Qiang

    2017-04-30

    Long-term exposure to a mechanical load causes degenerative changes in the disc nucleus pulposus (NP) tissue. A previous study demonstrated that N-cadherin (N-CDH)-mediated signalling can preserve the NP cell phenotype. However, N-CDH expression and the resulting phenotype alteration in NP cells under mechanical compression remain unclear. The present study investigated the effects of the compressive duration on N-CDH expression and on the phenotype of NP cells in an ex vivo disc organ culture. Porcine discs were organ cultured in a self-developed mechanically active bioreactor for 7 days. The discs were subjected to different dynamic compression durations (1 and 8 h at a magnitude of 0.4 MPa and frequency of 1.0 Hz) once per day. Discs that were not compressed were used as controls. The results showed that long-term compression duration (8 h) significantly down-regulated the expression of N-CDH and NP-specific molecule markers (Brachyury, Laminin, Glypican-3 and Keratin 19), attenuated Alcian Blue staining intensity, decreased glycosaminoglycan (GAG) and hydroxyproline (HYP) contents and decreased matrix macromolecule (aggrecan and collagen II) expression compared with the short-term compression duration (1 h). Taken together, these findings demonstrate that long-term load duration can induce N-CDH down-regulation, loss of normal cell phenotype and result in attenuation of NP-related matrix synthesis in NP cells. © 2017 The Author(s).

  10. Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baltazar, Ludmila Matos; Zamith-Miranda, Daniel; Burnet, Meagan C.

    Here, diverse pathogenic fungi secrete extracellular vesicles (EV) that contain macromolecules, including virulence factors that can modulate the host immune response. We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates how Histoplasma capsulatum load and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus’ EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV from H. capsulatum opsonizedmore » with 6B7 was reduced, but urease activity was not altered. The uptake of H. capsulatum by macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonized H. capsulatum and this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifies H. capsulatum EV load and secretion leading to distinct effects on the host’s immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells.« less

  11. Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages

    DOE PAGES

    Baltazar, Ludmila Matos; Zamith-Miranda, Daniel; Burnet, Meagan C.; ...

    2018-05-23

    Here, diverse pathogenic fungi secrete extracellular vesicles (EV) that contain macromolecules, including virulence factors that can modulate the host immune response. We recently demonstrated that the binding of monoclonal antibodies (mAb) modulates how Histoplasma capsulatum load and releases its extracellular vesicles (EV). In the present paper, we addressed a concentration-dependent impact on the fungus’ EV loading and release with different mAb, as well as the pathophysiological role of these EV during the host-pathogen interaction. We found that the mAbs differentially regulate EV content in concentration-dependent and independent manners. Enzymatic assays demonstrated that laccase activity in EV from H. capsulatum opsonizedmore » with 6B7 was reduced, but urease activity was not altered. The uptake of H. capsulatum by macrophages pre-treated with EV, presented an antibody concentration-dependent phenotype. The intracellular killing of yeast cells was potently inhibited in macrophages pre-treated with EV from 7B6 (non-protective) mAb-opsonized H. capsulatum and this inhibition was associated with a decrease in the reactive-oxygen species generated by these macrophages. In summary, our findings show that opsonization quantitatively and qualitatively modifies H. capsulatum EV load and secretion leading to distinct effects on the host’s immune effector mechanisms, supporting the hypothesis that EV sorting and secretion are dynamic mechanisms for a fine-tuned response by fungal cells.« less

  12. Citraturic response to oral citric acid load

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Alpern, R.; Poindexter, J.; Pak, C. Y.

    1992-01-01

    It is possible that some orally administered citrate may appear in urine by escaping oxidation in vivo. To determine whether this mechanism contributes to the citraturic response to potassium citrate, we measured serum and urinary citrate for 4 hours after a single oral load of citric acid (40 mEq.) in 6 normal subjects. Since citric acid does not alter acid-base balance, the effect of absorbed citrate could be isolated from that of alkali load. Serum citrate concentration increased significantly (p less than 0.05) 30 minutes after a single oral dose of citric acid and remained significantly elevated for 3 hours after citric acid load. Commensurate with this change, urinary citrate excretion peaked at 2 hours and gradually decreased during the next 2 hours after citric acid load. In contrast, serum and urinary citrate remained unaltered following the control load (no drug). Differences of the citratemic and citraturic effects between phases were significant (p less than 0.05) at 2 and 3 hours. Urinary pH, carbon dioxide pressure, bicarbonate, total carbon dioxide and ammonium did not change at any time after citric acid load, and did not differ between the 2 phases. No significant difference was noted in serum electrolytes, arterialized venous pH and carbon dioxide pressure at any time after citric acid load and between the 2 phases. Thus, the citraturic and citratemic effects of oral citric acid are largely accountable by provision of absorbed citrate, which has escaped in vivo degradation.

  13. First-principles investigation of mechanical properties of silicene, germanene and stanene

    NASA Astrophysics Data System (ADS)

    Mortazavi, Bohayra; Rahaman, Obaidur; Makaremi, Meysam; Dianat, Arezoo; Cuniberti, Gianaurelio; Rabczuk, Timon

    2017-03-01

    Two-dimensional allotropes of group-IV substrates including silicene, germanene and stanene have recently attracted considerable attention in nanodevice fabrication industry. These materials involving the buckled structure have been experimentally fabricated lately. In this study, first-principles density functional theory calculations were utilized to investigate the mechanical properties of single-layer and free-standing silicene, germanene and stanene. Uniaxial tensile and compressive simulations were carried out to probe and compare stress-strain properties; such as the Young's modulus, Poisson's ratio and ultimate strength. We evaluated the chirality effect on the mechanical response and bond structure of the 2D substrates. Our first-principles simulations suggest that in all studied samples application of uniaxial loading can alter the electronic nature of the buckled structures into the metallic character. Our investigation provides a general but also useful viewpoint with respect to the mechanical properties of silicene, germanene and stanene.

  14. Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy

    NASA Technical Reports Server (NTRS)

    Ingber, D. E.

    1992-01-01

    Angiogenesis, the growth of blood capillaries, is regulated by soluble growth factors and insoluble extracellular matrix (ECM) molecules. Soluble angiogenic mitogens act over large distances to initiate capillary growth whereas changes in ECM govern whether individual cells will grow, differentiate, or involute in response to these stimuli in the local tissue microenvironment. Analysis of this local control mechanism has revealed that ECM molecules switch capillary endothelial cells between differentiation and growth by both binding specific transmembrane integrin receptors and physically resisting cell-generated mechanical loads that are applied to these receptors. Control of capillary endothelial cell form and function therefore may be exerted by altering the mechanical properties of the ECM as well as its chemical composition. Understanding of this mechanochemical control mechanism has led to the development of new angiogenesis inhibitors that may be useful for the treatment of cancer.

  15. Reduced functional loads alter the physical characteristics of the bone-periodontal ligament-cementum complex.

    PubMed

    Niver, E L; Leong, N; Greene, J; Curtis, D; Ryder, M I; Ho, S P

    2011-12-01

    Adaptive properties of the bone-periodontal ligament-tooth complex have been identified by changing the magnitude of functional loads using small-scale animal models, such as rodents. Reported adaptive responses as a result of lower loads due to softer diet include decreased muscle development, change in structure-function relationship of the cranium, narrowed periodontal ligament space, and changes in the mineral level of the cortical bone and alveolar jaw bone and in the glycosaminoglycans of the alveolar bone. However, the adaptive role of the dynamic bone-periodontal ligament-cementum complex to prolonged reduced loads has not been fully explained to date, especially with regard to concurrent adaptations of bone, periodontal ligament and cementum. Therefore, in the present study, using a rat model, the temporal effect of reduced functional loads on physical characteristics, such as morphology and mechanical properties and the mineral profiles of the bone-periodontal ligament-cementum complex was investigated. Two groups of 6-wk-old male Sprague-Dawley rats were fed nutritionally identical food with a stiffness range of 127-158 N/mm for hard pellet or 0.3-0.5 N/mm for soft powder forms. Spatio-temporal adaptation of the bone-periodontal ligament-cementum complex was identified by mapping changes in the following: (i) periodontal ligament collagen orientation and birefringence using polarized light microscopy, bone and cementum adaptation using histochemistry, and bone and cementum morphology using micro-X-ray computed tomography; (ii) mineral profiles of the periodontal ligament-cementum and periodontal ligament-bone interfaces by X-ray attenuation; and (iii) microhardness of bone and cementum by microindentation of specimens at ages 6, 8, 12 and 15 wk. Reduced functional loads over prolonged time resulted in the following adaptations: (i) altered periodontal ligament orientation and decreased periodontal ligament collagen birefringence, indicating decreased periodontal ligament turnover rate and decreased apical cementum resorption; (ii) a gradual increase in X-ray attenuation, owing to mineral differences, at the periodontal ligament-bone and periodontal ligament-cementum interfaces, without significant differences in the gradients for either group; (iii) significantly (p < 0.05) lower microhardness of alveolar bone (0.93 ± 0.16 GPa) and secondary cementum (0.803 ± 0.13 GPa) compared with the higher load group insert bone = (1.10 ± 0.17 and cementum = 0.940 ± 0.15 GPa, respectively) at 15 wk, indicating a temporal effect of loads on the local mineralization of bone and cementum. Based on the results from this study, the effect of reduced functional loads for a prolonged time could differentially affect morphology, mechanical properties and mineral variations of the local load-bearing sites in the bone-periodontal ligament-cementum complex. These observed local changes in turn could help to explain the overall biomechanical function and adaptations of the tooth-bone joint. From a clinical translation perspective, our study provides an insight into modulation of load on the complex for improved tooth function during periodontal disease and/or orthodontic and prosthodontic treatments. © 2011 John Wiley & Sons A/S.

  16. CURRENT CONCEPTS IN BIOMECHANICAL INTERVENTIONS FOR PATELLOFEMORAL PAIN

    PubMed Central

    Meira, Erik P.

    2016-01-01

    Patellofemoral pain (PFP) has historically been a complex and enigmatic issue. Many of the factors thought to relate to PFP remain after patients' symptoms have resolved making their clinical importance difficult to determine. The tissue homeostasis model proposed by Dye in 2005 can assist with understanding and implementing biomechanical interventions for PFP. Under this model, the goal of interventions for PFP should be to re-establish patellofemoral joint (PFJ) homeostasis through a temporary alteration of load to the offended tissue, followed by incrementally restoring the envelope of function to the baseline level or higher. High levels of PFJ loads, particularly in the presence of an altered PFJ environment, are thought to be a factor in the development of PFP. Clinical interventions often aim to alter the biomechanical patterns that are thought to result in elevated PFJ loads while concurrently increasing the load tolerance capabilities of the tissue through therapeutic exercise. Biomechanics may play a role in PFJ load modification not only when addressing proximal and distal components, but also when considering the involvement of more local factors such as the quadriceps musculature. Biomechanical considerations should consider the entire kinetic chain including the hip and the foot/ankle complex, however the beneficial effects of these interventions may not be the result of long-term biomechanical changes. Biomechanical alterations may be achieved through movement retraining, but the interventions likely need to be task-specific to alter movement patterns. The purpose of this commentary is to describe biomechanical interventions for the athlete with PFP to encourage a safe and complete return to sport. Level of Evidence 5 PMID:27904791

  17. Hemodynamic Response Alterations in Sensorimotor Areas as a Function of Barbell Load Levels during Squatting: An fNIRS Study

    PubMed Central

    Kenville, Rouven; Maudrich, Tom; Carius, Daniel; Ragert, Patrick

    2017-01-01

    Functional near-infrared spectroscopy (fNIRS) serves as a promising tool to examine hemodynamic response alterations in a sports-scientific context. The present study aimed to investigate how brain activity within the human motor system changes its processing in dependency of different barbell load conditions while executing a barbell squat (BS). Additionally, we used different fNIRS probe configurations to identify and subsequently eliminate potential exercise induced systemic confounders such as increases in extracerebral blood flow. Ten healthy, male participants were enrolled in a crossover design. Participants performed a BS task with random barbell load levels (0% 1RM (1 repetition maximum), 20% 1RM and 40% 1RM for a BS) during fNIRS recordings. Initially, we observed global hemodynamic response alterations within and outside the human motor system. However, short distance channel regression of fNIRS data revealed a focalized hemodynamic response alteration within bilateral superior parietal lobe (SPL) for oxygenated hemoglobin (HbO2) and not for deoxygenated hemoglobin (HHb) when comparing different load levels. These findings indicate that the previously observed load/force-brain relationship for simple and isolated movements is also present in complex multi-joint movements such as the BS. Altogether, our results show the feasibility of fNIRS to investigate brain processing in a sports-related context. We suggest for future studies to incorporate short distance channel regression of fNIRS data to reduce the likelihood of false-positive hemodynamic response alterations during complex whole movements. PMID:28555098

  18. Force feedback controls motor activity and mechanical properties of self-assembling branched actin networks

    PubMed Central

    Bieling, Peter; Li, Tai-De; Weichsel, Julian; McGorty, Ryan; Jreij, Pamela; Huang, Bo; Fletcher, Daniel A.; Mullins, R. Dyche

    2016-01-01

    Branched actin networks–created by the Arp2/3 complex, capping protein, and a nucleation promoting factor– generate and transmit forces required for many cellular processes, but their response to force is poorly understood. To address this, we assembled branched actin networks in vitro from purified components and used simultaneous fluorescence and atomic force microscopy to quantify their molecular composition and material properties under various forces. Remarkably, mechanical loading of these self-assembling materials increases their density, power, and efficiency. Microscopically, increased density reflects increased filament number and altered geometry, but no change in average length. Macroscopically, increased density enhances network stiffness and resistance to mechanical failure beyond those of isotropic actin networks. These effects endow branched actin networks with memory of their mechanical history that shapes their material properties and motor activity. This work reveals intrinsic force feedback mechanisms by which mechanical resistance makes self-assembling actin networks stiffer, stronger, and more powerful. PMID:26771487

  19. Multi-time scale dynamics in power electronics-dominated power systems

    NASA Astrophysics Data System (ADS)

    Yuan, Xiaoming; Hu, Jiabing; Cheng, Shijie

    2017-09-01

    Electric power infrastructure has recently undergone a comprehensive transformation from electromagnetics to semiconductors. Such a development is attributed to the rapid growth of power electronic converter applications in the load side to realize energy conservation and on the supply side for renewable generations and power transmissions using high voltage direct current transmission. This transformation has altered the fundamental mechanism of power system dynamics, which demands the establishment of a new theory for power system control and protection. This paper presents thoughts on a theoretical framework for the coming semiconducting power systems.

  20. Muscle contributions to medial tibiofemoral compartment contact loading following ACL reconstruction using semitendinosus and gracilis tendon grafts.

    PubMed

    Konrath, Jason M; Saxby, David J; Killen, Bryce A; Pizzolato, Claudio; Vertullo, Christopher J; Barrett, Rod S; Lloyd, David G

    2017-01-01

    The muscle-tendon properties of the semitendinosus (ST) and gracilis (GR) are substantially altered following tendon harvest for the purpose of anterior cruciate ligament reconstruction (ACLR). This study adopted a musculoskeletal modelling approach to determine how the changes to the ST and GR muscle-tendon properties alter their contribution to medial compartment contact loading within the tibiofemoral joint in post ACLR patients, and the extent to which other muscles compensate under the same external loading conditions during walking, running and sidestep cutting. Motion capture and electromyography (EMG) data from 16 lower extremity muscles were acquired during walking, running and cutting in 25 participants that had undergone an ACLR using a quadruple (ST+GR) hamstring auto-graft. An EMG-driven musculoskeletal model was used to estimate the medial compartment contact loads during the stance phase of each gait task. An adjusted model was then created by altering muscle-tendon properties for the ST and GR to reflect their reported changes following ACLR. Parameters for the other muscles in the model were calibrated to match the experimental joint moments. The medial compartment contact loads for the standard and adjusted models were similar. The combined contributions of ST and GR to medial compartment contact load in the adjusted model were reduced by 26%, 17% and 17% during walking, running and cutting, respectively. These deficits were balanced by increases in the contribution made by the semimembranosus muscle of 33% and 22% during running and cutting, respectively. Alterations to the ST and GR muscle-tendon properties in ACLR patients resulted in reduced contribution to medial compartment contact loads during gait tasks, for which the semimembranosus muscle can compensate.

  1. Climate change and wetland loss impacts on a western river's water quality

    NASA Astrophysics Data System (ADS)

    Records, R. M.; Arabi, M.; Fassnacht, S. R.; Duffy, W. G.; Ahmadi, M.; Hegewisch, K. C.

    2014-11-01

    An understanding of potential stream water quality conditions under future climate is critical for the sustainability of ecosystems and the protection of human health. Changes in wetland water balance under projected climate could alter wetland extent or cause wetland loss (e.g., via increased evapotranspiration and lower growing season flows leading to reduced riparian wetland inundation) or altered land use patterns. This study assessed the potential climate-induced changes to in-stream sediment and nutrient loads in the snowmelt-dominated Sprague River, Oregon, western US. Additionally, potential water quality impacts of combined changes in wetland water balance and wetland area under future climatic conditions were evaluated. The study utilized the Soil and Water Assessment Tool (SWAT) forced with statistical downscaling of general circulation model (GCM) data from the Coupled Model Intercomparison Project 5 (CMIP5) using the Multivariate Adaptive Constructed Analogs (MACA) method. Our findings suggest that, in the Sprague River, (1) mid-21st century nutrient and sediment loads could increase significantly during the high-flow season under warmer, wetter climate projections or could change only nominally in a warmer and somewhat drier future; (2) although water quality conditions under some future climate scenarios and no wetland loss may be similar to the past, the combined impact of climate change and wetland losses on nutrient loads could be large; (3) increases in stream total phosphorus (TP) concentration with wetland loss under future climate scenarios would be greatest at high-magnitude, low-probability flows; and (4) loss of riparian wetlands in both headwaters and lowlands could increase outlet TP loads to a similar degree, but this could be due to distinctly different mechanisms in different parts of the watershed.

  2. Multifactorial causal model of brain (dis)organization and therapeutic intervention: Application to Alzheimer's disease.

    PubMed

    Iturria-Medina, Yasser; Carbonell, Félix M; Sotero, Roberto C; Chouinard-Decorte, Francois; Evans, Alan C

    2017-05-15

    Generative models focused on multifactorial causal mechanisms in brain disorders are scarce and generally based on limited data. Despite the biological importance of the multiple interacting processes, their effects remain poorly characterized from an integrative analytic perspective. Here, we propose a spatiotemporal multifactorial causal model (MCM) of brain (dis)organization and therapeutic intervention that accounts for local causal interactions, effects propagation via physical brain networks, cognitive alterations, and identification of optimum therapeutic interventions. In this article, we focus on describing the model and applying it at the population-based level for studying late onset Alzheimer's disease (LOAD). By interrelating six different neuroimaging modalities and cognitive measurements, this model accurately predicts spatiotemporal alterations in brain amyloid-β (Aβ) burden, glucose metabolism, vascular flow, resting state functional activity, structural properties, and cognitive integrity. The results suggest that a vascular dysregulation may be the most-likely initial pathologic event leading to LOAD. Nevertheless, they also suggest that LOAD it is not caused by a unique dominant biological factor (e.g. vascular or Aβ) but by the complex interplay among multiple relevant direct interactions. Furthermore, using theoretical control analysis of the identified population-based multifactorial causal network, we show the crucial advantage of using combinatorial over single-target treatments, explain why one-target Aβ based therapies might fail to improve clinical outcomes, and propose an efficiency ranking of possible LOAD interventions. Although still requiring further validation at the individual level, this work presents the first analytic framework for dynamic multifactorial brain (dis)organization that may explain both the pathologic evolution of progressive neurological disorders and operationalize the influence of multiple interventional strategies. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effects of expectation congruency on event-related potentials (ERPs) to facial expressions depend on cognitive load during the expectation phase.

    PubMed

    Lin, Huiyan; Schulz, Claudia; Straube, Thomas

    2016-10-01

    Previous studies have shown that event-related potentials (ERPs) to facial expressions are modulated by expectation (congruency) and that the ERP effects of expectation congruency are altered by cognitive tasks during the expectation phase. However, it is as yet unknown whether the congruency ERP effects can be modulated by the amount of cognitive load during the expectation phase. To address this question, electroencephalogram (EEG) was acquired when participants viewed fearful and neutral facial expressions. Before the presentation of facial expressions, a cue indicating the expression of a face and subsequently, an expectation interval without any cues were presented. Facial expressions were congruent with the cues in 75% of all trials. During the expectation interval, participants had to solve a cognitive task, in which several letters were presented for target letter detection. The letters were all the same under low load, but differed under high load. Event-related potential (ERP) results showed that the amount of cognitive load during the expectation phase altered the congruency effect in N2 and EPN amplitudes for fearful faces. Congruent as compared to incongruent fearful expressions elicited larger N2 and smaller EPN amplitudes under low load, but these congruency effects were not observed under high load. For neutral faces, a congruency effect in late positive potential (LPP) amplitudes was modulated by cognitive load during the expectation phase. The LPP was more positive for incongruent as compared to congruent faces under low load, but the congruency effect was not evident under high load. The findings indicate that congruency effects on ERPs are modulated by the amount of cognitive load the expectation phase and that this modulation is altered by facial expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Attritional wear and abrasive surface alterations of composite resin materials in vitro.

    PubMed

    Göhring, T N; Besek, M J; Schmidlin, P R

    2002-01-01

    A laboratory study was performed with 232 specimens and 72 human enamel, 24 gold, 24 ceramic and 12 composite antagonists in 22 groups to test attritional and abrasive wear behavior of composite materials compared to wear behavior of human enamel. Belleglass HP, Concept Inlay/Onlay, Targis and Targis Upgrade 99 composite resin for lab-made restorations was tested as well as Tetric Ceram and FHC Merz light as resins for direct restorations. Natural human enamel specimens served as control. All specimens were subjected to long-term thermo-mechanical loading in a computer-controlled masticator, chemical degradation and toothbrush/toothpaste abrasion. Wear of specimen in occlusal contact area (OCA), contact-free occlusal area and wear of natural enamel cusps as well as antagonists made of gold, ceramic and composite in identical form was measured after 120,000, 240,000, 640,000 and 1200,000 load cycles. A qualitative SEM analysis was performed to support quantitative data. Belleglass HP and Targis Upgrade 99 restorative materials showed wear resistance comparable to human enamel when loaded with enamel cusps. Wear of Targis versus composite and gold antagonists was significantly higher (p<0.0001). Analysis of surface alterations showed hygroscopic expansion in all composite resins during the test. As a consequence of this study, necessity to further improve physical properties of composites for long lasting restorations was obvious. Beside of attritional wear in OCA, attention must be given to stable filler-matrix interfaces and prevention of water sorption.

  5. Strain rate effects on fracture behavior of Austempered Ductile Irons

    NASA Astrophysics Data System (ADS)

    Ruggiero, Andrew; Bonora, Nicola; Gentile, Domenico; Iannitti, Gianluca; Testa, Gabriel; Hörnqvist Colliander, Magnus; Masaggia, Stefano; Vettore, Federico

    2017-06-01

    Austempered Ductile Irons (ADIs), combining high strength, good ductility and low density, are candidates to be a suitable alternative to high-strength steels. Nevertheless, the concern about a low ductility under dynamic loads often leads designers to exclude cast irons for structural applications. However, results from dynamic tensile tests contradict this perception showing larger failure strain with respect to quasistatic data. The fracture behaviour of ADIs depends on damage mechanisms occurring in the spheroids of graphite, in the matrix and at their interface, with the matrix (ausferrite) consisting of acicular ferrite in carbon-enriched austenite. Here, a detailed microstructural analysis was performed on the ADI 1050-6 deformed under different conditions of strain rates, temperatures, and states of stress. Beside the smooth specimens used for uniaxial tensile tests, round notched bars to evaluate the ductility reduction with increasing stress triaxiality and tophat geometries to evaluate the propensity to shear localization and the associated microstructural alterations were tested. The aim of the work is to link the mechanical and fracture behavior of ADIs to the load condition through the microstructural modifications that occur for the corresponding deformation path.

  6. Application of Systems Theory in Longitudinal Studies on the Origin and Progression of Alzheimer's Disease.

    PubMed

    Lista, Simone; Khachaturian, Zaven S; Rujescu, Dan; Garaci, Francesco; Dubois, Bruno; Hampel, Harald

    2016-01-01

    This chapter questions the prevailing "implicit" assumption that molecular mechanisms and the biological phenotype of dominantly inherited early-onset alzheimer's disease (EOAD) could serve as a linear model to study the pathogenesis of sporadic late-onset alzheimer's disease (LOAD). Now there is growing evidence to suggest that such reductionism may not be warranted; these suppositions are not adequate to explain the molecular complexities of LOAD. For example, the failure of some recent amyloid-centric clinical trials, which were largely based on the extrapolations from EOAD biological phenotypes to the molecular mechanisms in the pathogenesis of LOAD, might be due to such false assumptions. The distinct difference in the biology of LOAD and EOAD is underscored by the presence of EOAD cases without evidence of familial clustering or Mendelian transmission and, conversely, the discovery and frequent reports of such clustering and transmission patterns in LOAD cases. The primary thesis of this chapter is that a radically different way of thinking is required for comprehensive explanations regarding the distinct complexities in the molecular pathogenesis of inherited and sporadic forms of Alzheimer's disease (AD). We propose using longitudinal analytical methods and the paradigm of systems biology (using transcriptomics, proteomics, metabolomics, and lipidomics) to provide us a more comprehensive insight into the lifelong origin and progression of different molecular mechanisms and neurodegeneration. Such studies should aim to clarify the role of specific pathophysiological and signaling pathways such as neuroinflammation, altered lipid metabolism, apoptosis, oxidative stress, tau hyperphosphorylation, protein misfolding, tangle formation, and amyloidogenic cascade leading to overproduction and reduced clearance of aggregating amyloid-beta (Aβ) species. A more complete understanding of the distinct difference in molecular mechanisms, signaling pathways, as well as comparability of the various forms of AD is of paramount importance. The development of knowledge and technologies for early detection and characterization of the disease across all stages will improve the predictions regarding the course of the disease, prognosis, and response to treatment. No doubt such advances will have a significant impact on the clinical management of both EOAD and LOAD patients. The approach propped here, combining longitudinal studies with the systems biology paradigm, will create a more effective and comprehensive framework for development of prevention therapies in AD.

  7. PATIENT-SPECIFIC FINITE ELEMENT ANALYSIS OF CHRONIC CONTACT STRESS EXPOSURE AFTER INTRA-ARTICULAR FRACTURE OF THE TIBIAL PLAFOND

    PubMed Central

    Li, Wendy; Anderson, Donald D.; Goldsworthy, Jane K.; Marsh, J. Lawrence; Brown, Thomas D.

    2008-01-01

    SUMMARY The role of altered contact mechanics in the pathogenesis of post-traumatic osteoarthritis (PTOA) following intra-articular fracture remains poorly understood. One proposed etiology is that residual incongruities lead to altered joint contact stresses that, over time, predispose to PTOA. Prevailing joint contact stresses following surgical fracture reduction were quantified in this study using patient-specific contact finite element (FE) analysis. FE models were created for 11 ankle pairs from tibial plafond fracture patients. Both (reduced) fractured ankles and their intact contralaterals were modeled. A sequence of 13 loading instances was used to simulate the stance phase of gait. Contact stresses were summed across loadings in the simulation, weighted by resident time in the gait cycle. This chronic exposure measure, a metric of degeneration propensity, was then compared between intact and fractured ankle pairs. Intact ankles had lower peak contact stress exposures that were more uniform, and centrally located. The series-average peak contact stress elevation for fractured ankles was 38% (p=0.0015; peak elevation was 82%). Fractured ankles had less area with low contact stress exposure than intacts, and a greater area with high exposure. Chronic contact stress overexposures (stresses exceeding a damage threshold) ranged from near zero to a high of 18 times the matched intact value. The patient-specific FE models utilized in this study represent substantial progress towards elucidating the relationship between altered contact stresses and the outcome of patients treated for intra-articular fractures. PMID:18404662

  8. Electro-mechanical response of a 3D nerve bundle model to mechanical loads leading to axonal injury.

    PubMed

    Cinelli, I; Destrade, M; Duffy, M; McHugh, P

    2017-07-01

    Axonal damage is one of the most common pathological features of traumatic brain injury, leading to abnormalities in signal propagation for nervous systems. We present a 3D fully coupled electro-mechanical model of a nerve bundle, made with the finite element software Abaqus 6.13-3. The model includes a real-time coupling, modulated threshold for spiking activation and independent alteration of the electrical properties for each 3-layer fibre within the bundle. Compression and tension are simulated to induce damage at the nerve membrane. Changes in strain, stress distribution and neural activity are investigated for myelinated and unmyelinated nerve fibres, by considering the cases of an intact and of a traumatized nerve membrane. Results show greater changes in transmitting action potential in the myelinated fibre.

  9. Fruit load governs transpiration of olive trees

    PubMed Central

    Bustan, Amnon; Dag, Arnon; Yermiyahu, Uri; Erel, Ran; Presnov, Eugene; Agam, Nurit; Kool, Dilia; Iwema, Joost; Zipori, Isaac; Ben-Gal, Alon

    2016-01-01

    We tested the hypothesis that whole-tree water consumption of olives (Olea europaea L.) is fruit load-dependent and investigated the driving physiological mechanisms. Fruit load was manipulated in mature olives grown in weighing-drainage lysimeters. Fruit was thinned or entirely removed from trees at three separate stages of growth: early, mid and late in the season. Tree-scale transpiration, calculated from lysimeter water balance, was found to be a function of fruit load, canopy size and weather conditions. Fruit removal caused an immediate decline in water consumption, measured as whole-plant transpiration normalized to tree size, which persisted until the end of the season. The later the execution of fruit removal, the greater was the response. The amount of water transpired by a fruit-loaded tree was found to be roughly 30% greater than that of an equivalent low- or nonyielding tree. The tree-scale response to fruit was reflected in stem water potential but was not mirrored in leaf-scale physiological measurements of stomatal conductance or photosynthesis. Trees with low or no fruit load had higher vegetative growth rates. However, no significant difference was observed in the overall aboveground dry biomass among groups, when fruit was included. This case, where carbon sources and sinks were both not limiting, suggests that the role of fruit on water consumption involves signaling and alterations in hydraulic properties of vascular tissues and tree organs. PMID:26802540

  10. Effects of two neuromuscular training programs on running biomechanics with load carriage: a study protocol for a randomised controlled trial.

    PubMed

    Liew, Bernard X W; Morris, Susan; Keogh, Justin W L; Appleby, Brendyn; Netto, Kevin

    2016-10-22

    In recent years, athletes have ventured into ultra-endurance and adventure racing events, which tests their ability to race, navigate, and survive. These events often require race participants to carry some form of load, to bear equipment for navigation and survival purposes. Previous studies have reported specific alterations in biomechanics when running with load which potentially influence running performance and injury risk. We hypothesize that a biomechanically informed neuromuscular training program would optimize running mechanics during load carriage to a greater extent than a generic strength training program. This will be a two group, parallel randomized controlled trial design, with single assessor blinding. Thirty healthy runners will be recruited to participate in a six weeks neuromuscular training program. Participants will be randomized into either a generic training group, or a biomechanically informed training group. Primary outcomes include self-determined running velocity with a 20 % body weight load, jump power, hopping leg stiffness, knee extensor and triceps-surae strength. Secondary outcomes include running kinetics and kinematics. Assessments will occur at baseline and post-training. To our knowledge, no training programs are available that specifically targets a runner's ability to carry load while running. This will provide sport scientists and coaches with a foundation to base their exercise prescription on. ANZCTR ( ACTRN12616000023459 ) (14 Jan 2016).

  11. Friction and wear behaviour of plasma sprayed Cr2O3-TiO2 coating

    NASA Astrophysics Data System (ADS)

    Bagde, Pranay; Sapate, S. G.; Khatirkar, R. K.; Vashishtha, Nitesh; Tailor, Satish

    2018-02-01

    Cr2O3-25TiO2 coating was deposited by atmospheric plasma spray (APS) coating technique. Effect of load (5-30 N) and sliding velocity (0.25, 0.75 m s-1) on friction coefficient and abrasive wear behaviour of the Cr2O3-25TiO2 coating was studied. Mechanical and microstructural characterization of the Cr2O3-25TiO2 coating was carried out. With an increase in sliding velocity, abrasive wear rate and friction coefficient (COF) decreased while wear rate and friction coefficient showed an increasing trend with the load. The worn out surfaces were analyzed by SEM, EDS and XRD. At lower sliding velocity, XRD analysis revealed peaks of Ti2O3, Ti3O5, CrO2 and CrO3. In addition, peak of Ti4O7 was also detected at higher sliding velocity and at 30 N load. At higher sliding velocity medium to severe tribo oxidation was observed. XPS analysis of worn surfaces at both the sliding velocities, showed surface film of oxides of titanium and chromium along with Cr(OH)3. Magneli phase titanium oxides with sub stoichiometric composition, along with surface films of chromium oxides and hydroxides altered the friction and wear behaviour of the coating. The decrease in friction coefficient with an increase in sliding velocity was attributed to tribo oxides and tribochemical reaction films having lower shear strength with good lubricating properties. The mechanism of material removal involved plastic deformation at lower load whereas inter-granular and trans-granular fracture, delamination cracking and splat fracture was observed with an increase load from 10 N to 30 N.

  12. Finite element analysis on the biomechanical stability of open porous titanium scaffolds for large segmental bone defects under physiological load conditions.

    PubMed

    Wieding, Jan; Souffrant, Robert; Mittelmeier, Wolfram; Bader, Rainer

    2013-04-01

    Repairing large segmental defects in long bones caused by fracture, tumour or infection is still a challenging problem in orthopaedic surgery. Artificial materials, i.e. titanium and its alloys performed well in clinical applications, are plenary available, and can be manufactured in a wide range of scaffold designs. Although the mechanical properties are determined, studies about the biomechanical behaviour under physiological loading conditions are rare. The goal of our numerical study was to determine the suitability of open-porous titanium scaffolds to act as bone scaffolds. Hence, the mechanical stability of fourteen different scaffold designs was characterized under both axial compression and biomechanical loading within a large segmental distal femoral defect of 30mm. This defect was stabilized with an osteosynthesis plate and physiological hip reaction forces as well as additional muscle forces were implemented to the femoral bone. Material properties of titanium scaffolds were evaluated from experimental testing. Scaffold porosity was varied between 64 and 80%. Furthermore, the amount of material was reduced up to 50%. Uniaxial compression testing revealed a structural modulus for the scaffolds between 3.5GPa and 19.1GPa depending on porosity and material consumption. The biomechanical testing showed defect gap alterations between 0.03mm and 0.22mm for the applied scaffolds and 0.09mm for the intact bone. Our results revealed that minimizing the amount of material of the inner core has a smaller influence than increasing the porosity when the scaffolds are loaded under biomechanical loading. Furthermore, an advanced scaffold design was found acting similar as the intact bone. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

  13. Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy

    PubMed Central

    Abel, E. Dale; Doenst, Torsten

    2011-01-01

    Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences. PMID:21257612

  14. Shear load transfer in high and low stress tendons.

    PubMed

    Kondratko-Mittnacht, Jaclyn; Duenwald-Kuehl, Sarah; Lakes, Roderic; Vanderby, Ray

    2015-05-01

    Tendon is an integral part of joint movement and stability, as it functions to transmit load from muscle to bone. It has an anisotropic, fibrous hierarchical structure that is generally loaded in the direction of its fibers/fascicles. Internal load distributions are altered when joint motion rotates an insertion site or when local damage disrupts fibers/fascicles, potentially causing inter-fiber (or inter-fascicular) shear. Tendons with different microstructures (helical versus linear) may redistribute loads differently. This study explored how shear redistributes axial loads in rat tail tendon (low stress tendons with linear microstructure) and porcine flexor tendon (high stress with helical microstructure) by creating lacerations on opposite sides of the tendon, ranging from about 20% to 60% of the tendon width, to create various magnitudes of shear. Differences in fascicular orientation were quantified using polarized light microscopy. Unexpectedly, both tendon types maintained about 20% of pre-laceration stress values after overlapping cuts of 60% of tendon width (no intact fibers end to end) suggesting that shear stress transfer can contribute more to overall tendon strength and stiffness than previously reported. All structural parameters for both tendon types decreased linearly with increasing laceration depth. The tail tendon had a more rapid decline in post-laceration elastic stress and modulus parameters as well as a more linear and less tightly packed fascicular structure, suggesting that positional tendons may be less well suited to redistribute loads via a shear mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Shear Load Transfer in High and Low Stress Tendons

    PubMed Central

    Kondratko-Mittnacht, Jaclyn; Duenwald-Kuehl, Sarah; Lakes, Roderic; Vanderby, Ray

    2016-01-01

    Background Tendon is an integral part of joint movement and stability, as it functions to transmit load from muscle to bone. It has an anisotropic, fibrous hierarchical structure that is generally loaded in the direction of its fibers/fascicles. Internal load distributions are altered when joint motion rotates an insertion site or when local damage disrupts fibers/fascicles, potentially causing inter-fiber (or inter-fascicular) shear. Tendons with different microstructure (helical versus linear) may redistribute loads differently. Method of Approach This study explored how shear redistributes axial loads in rat tail tendon (low stress tendons with linear microstructure) and porcine flexor tendon (high stress with helical microstructure) by creating lacerations on opposite sides of the tendon, ranging from about 20-60% of the tendon width, to create various magnitudes of shear. Differences in fascicular orientation were quantified using polarized light microscopy. Results and Conclusions Unexpectedly, both tendon types maintained about 20% of pre-laceration stress values after overlapping cuts of 60% of tendon width (no intact fibers end to end) suggesting that shear stress transfer can contribute more to overall tendon strength and stiffness than previously reported. All structural parameters for both tendon types decreased linearly with increasing laceration depth. The tail tendon had a more rapid decline in post-laceration elastic stress and modulus parameters as well as a more linear and less tightly packed fascicular structure, suggesting that positional tendons may be less well suited to redistribute loads via a shear mechanism. PMID:25700261

  16. Changed morphology and mechanical properties of cancellous bone in the mandibular condyles of edentate people.

    PubMed

    Giesen, E B W; Ding, M; Dalstra, M; van Eijden, T M G J

    2004-03-01

    Since edentate subjects have a reduced masticatory function, it can be expected that the morphology of the cancellous bone of their mandibular condyles has changed according to the altered mechanical environment. In the present study, the morphology of cylindrical cancellous bone specimens of the mandibular condyles of edentate subjects (n = 25) was compared with that of dentate subjects (n = 24) by means of micro-computed tomography and by the application of Archimedes' principle. Stiffness and strength were determined by destructive mechanical testing. Compared with dentate subjects, it appeared that, in edentate subjects, the bone was less dense and the trabecular structure was less plate-like. The regression models of stiffness and strength built from bone volume fraction and the trabecular orientation relative to the axis of the specimen were similar for both dentate and edentate subjects. This indicates that, under reduced mechanical load, the fundamental relationship between bone morphology and mechanical properties does not change.

  17. Ocular Drug Delivery through pHEMA-Hydrogel Contact Lenses Co-Loaded with Lipophilic Vitamins

    NASA Astrophysics Data System (ADS)

    Lee, Dasom; Cho, Seungkwon; Park, Hwa Sung; Kwon, Inchan

    2016-09-01

    Ocular drug delivery through hydrogel contact lenses has great potential for the treatment of ocular diseases. Previous studies showed that the loading of lipophilic vitamin E to silicone-hydrogel contact lenses was beneficial in ocular drug delivery. We hypothesized that vitamin E loading to another type of popular hydrogel contact lenses, pHEMA-hydrogel contact lenses, improves ocular drug delivery by increasing the drug loading or the duration of drug release. Loading of vitamin E to pHEMA-hydrogel contact lenses significantly increased the loading of a hydrophilic drug surrogate (Alexa Fluor 488 dye) and two hydrophilic glaucoma drugs (timolol and brimonidine) to the lenses by 37.5%, 19.1%, and 18.7%, respectively. However, the release duration time was not significantly altered. Next, we hypothesized that the lipophilic nature of vitamin E attributes to the enhanced drug loading. Therefore, we investigated the effects of co-loading of another lipophilic vitamin, vitamin A, on drug surrogate delivery. We found out that vitamin A loading also increased the loading of the drug surrogate to pHEMA-hydrogel contact lenses by 30.3%. Similar to vitamin E loading, vitamin A loading did not significantly alter the release duration time of the drug or drug surrogate.

  18. Load sharing in bioinspired fibrillar adhesives with backing layer interactions and interfacial misalignment

    NASA Astrophysics Data System (ADS)

    Bacca, Mattia; Booth, Jamie A.; Turner, Kimberly L.; McMeeking, Robert M.

    2016-11-01

    Bio-inspired fibrillar adhesives rely on the utilization of short-range intermolecular forces harnessed by intimate contact at fibril tips. The combined adhesive strength of multiple fibrils can only be utilized if equal load sharing (ELS) is obtained at detachment. Previous investigations have highlighted that mechanical coupling of fibrils through a compliant backing layer gives rise to load concentration and the nucleation and propagation of interfacial flaws. However, misalignment of the adhesive and contacting surface has not been considered in theoretical treatments of load sharing with backing layer interactions. Alignment imperfections are difficult to avoid for a flat-on-flat interfacial configuration. In this work we demonstrate that interfacial misalignment can significantly alter load sharing and the kinematics of detachment in a model adhesive system. Load sharing regimes dominated by backing layer interactions and misalignment are revealed, the transition between which is controlled by the misalignment angle, fibril separation, and fibril compliance. In the regime dominated by misalignment, backing layer deformation can counteract misalignment giving rise to improved load sharing when compared to an identical fibrillar array with a rigid backing layer. This result challenges the conventional belief that stiffer (and thinner) backing layers consistently reduce load concentration among fibrils. Finally, we obtain analytically the fibril compliance distribution required to harness backing layer interactions to obtain ELS. Through fibril compliance optimization, ELS can be obtained even with misalignment. However, since misalignment is typically not deterministic, it is of greater practical significance that the array optimized for perfect alignment exhibits load sharing superior to that of a homogeneous array subject to misalignment. These results inform the design of fibrillar arrays with graded compliance capable of exhibiting improved load sharing over large areas.

  19. Anti-gravity treadmill can promote aerobic exercise for lower limb osteoarthritis patients

    PubMed Central

    Kawae, Toshihiro; Mikami, Yukio; Fukuhara, Kouki; Kimura, Hiroaki; Adachi, Nobuo

    2017-01-01

    [Purpose] The anti-gravity treadmill (Alter-G®) allows the load on the lower limbs to be adjusted, which is considered useful for patients with lower limb osteoarthritis. The aim of the present study was to examine the effects of aerobic exercise using an anti-gravity treadmill in patients with lower limb osteoarthritis by using a cardiopulmonary exercise load monitoring system. [Subjects and Methods] The subjects were 20 patients with lower limb osteoarthritis. These subjects walked naturally for 8 minutes and then walked on the Alter-G for 8 minutes at their fastest speed at a load where lower limb pain was alleviated. [Results] Subjective and objective exercise intensity did not differ significantly between level ground walking and Alter-G walking neither before nor after walking. Pain before walking did not differ significantly between level ground walking and Alter-G walking, but pain after walking was significantly greater with level ground walking than with Alter-G walking. [Conclusion] Exercise therapy using an anti-gravity treadmill was useful for patients with lower limb osteoarthritis in terms of cardiopulmonary function, which suggested that this could become a new form of exercise therapy. PMID:28878480

  20. Anti-gravity treadmill can promote aerobic exercise for lower limb osteoarthritis patients.

    PubMed

    Kawae, Toshihiro; Mikami, Yukio; Fukuhara, Kouki; Kimura, Hiroaki; Adachi, Nobuo

    2017-08-01

    [Purpose] The anti-gravity treadmill (Alter-G ® ) allows the load on the lower limbs to be adjusted, which is considered useful for patients with lower limb osteoarthritis. The aim of the present study was to examine the effects of aerobic exercise using an anti-gravity treadmill in patients with lower limb osteoarthritis by using a cardiopulmonary exercise load monitoring system. [Subjects and Methods] The subjects were 20 patients with lower limb osteoarthritis. These subjects walked naturally for 8 minutes and then walked on the Alter-G for 8 minutes at their fastest speed at a load where lower limb pain was alleviated. [Results] Subjective and objective exercise intensity did not differ significantly between level ground walking and Alter-G walking neither before nor after walking. Pain before walking did not differ significantly between level ground walking and Alter-G walking, but pain after walking was significantly greater with level ground walking than with Alter-G walking. [Conclusion] Exercise therapy using an anti-gravity treadmill was useful for patients with lower limb osteoarthritis in terms of cardiopulmonary function, which suggested that this could become a new form of exercise therapy.

  1. Cortical Drive to Breathe during Wakefulness in Patients with Obstructive Sleep Apnea Syndrome.

    PubMed

    Launois, Claire; Attali, Valérie; Georges, Marjolaine; Raux, Mathieu; Morawiec, Elise; Rivals, Isabelle; Arnulf, Isabelle; Similowski, Thomas

    2015-11-01

    The obstructive sleep apnea syndrome (OSAS) involves recurrent sleep-related upper airways (UA) collapse. UA mechanical properties and neural control are altered, imposing a mechanical load on inspiration. UA collapse does not occur during wakefulness, hence arousal-dependent compensation. Experimental inspiratory loading in normal subjects elicits respiratory-related cortical activity. The objective of this study was to test whether awake OSAS patients would exhibit a similar cortical activity. Descriptive physiology study. Sleep laboratory in a large university affiliated tertiary hospital. 26 patients with moderate OSAS according to polysomnography (5 < apnea-hypopnea index [AHI] ≤ 30, n = 14) or severe OSAS (AHI > 30, n = 12); 13 non-OSAS patients for comparison. None. Respiratory time-locked electroencephalographic segments ensemble averaged and analyzed for slow premotor potentials preceding inspiration ("pre-inspiratory potentials" [PIPs]). PIPs were present in 1/13 controls and 11/26 patients (P = 0.0336; 4/14 "moderate" and 7/12 "severe" patients). Awake OSAS patients therefore exhibit respiratory-related cortical activity during quiet breathing significantly more frequently than non-OSAS individuals. The corresponding PIPs resemble those observed during prepared voluntary inspirations and in response to experimental inspiratory loads in normal subjects, which involve a cortical network comprising the supplementary motor area. A respiratory-related cortical activity could contribute to the increased neural drive to upper airway and to inspiratory muscles that has previously been described in obstructive sleep apnea, and could therefore contribute to the arousal-dependent compensation of upper airway abnormalities. Whether or not such cortical compensatory mechanisms have cognitive consequences remains to be determined. © 2015 Associated Professional Sleep Societies, LLC.

  2. Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

    PubMed

    Natsuga, Ken; Cipolat, Sara; Watt, Fiona M

    2016-01-01

    Mice lacking three epidermal barrier proteins-envoplakin, periplakin, and involucrin (EPI-/- mice)-have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4(+) T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Osteochondral microdamage from valgus bending of the human knee.

    PubMed

    Meyer, Eric G; Villwock, Mark R; Haut, Roger C

    2009-08-01

    Valgus bending of the knee is promoted as an anterior cruciate ligament injury mechanism and is associated with a characteristic "footprint" of bone bruising. The hypothesis of this study was that during ligamentous failure caused by valgus bending of the knee, high tibiofemoral contact pressures induce acute osteochondral microdamage. Four knee pairs were loaded in valgus bending until gross injury with or without a tibiofemoral compression pre-load. The peak valgus moment and resultant motions of the knee joint were recorded. Pressure sensitive film documented the magnitude and location of tibiofemoral contact. Cartilage fissures were documented on the tibial plateau, and microcracks in subchondral bone were documented from micro-computed tomography scans. Injuries were to the anterior cruciate ligament in three knees and the medial collateral ligament in seven knees. The mean (standard deviation) peak bending moment at failure was 107 (64)Nm. Valgus bending produced regions of contact on the lateral tibial plateau with average maximum pressures of approximately 30 (8)MPa. Cartilage fissures and subchondral bone microcracks were observed in these regions of high contact pressure. Combined valgus bending and tibiofemoral compression produce slightly higher contact pressures, but do not alter the gross injury pattern from isolated valgus bending experiments. Athletes who sustain a severe valgus knee bending moment, may be at risk of acute osteochondral damage especially if the loading mechanism occurs with a significant tibiofemoral compression component.

  4. Mechanisms of Active Aerodynamic Load Reduction on a Rotorcraft Fuselage With Rotor Effects

    NASA Technical Reports Server (NTRS)

    Schaeffler, Norman W.; Allan, Brian G.; Jenkins, Luther N.; Yao, Chung-Sheng; Bartram, Scott M.; Mace, W. Derry; Wong, Oliver D.; Tanner, Philip E.

    2016-01-01

    The reduction of the aerodynamic load that acts on a generic rotorcraft fuselage by the application of active flow control was investigated in a wind tunnel test conducted on an approximately 1/3-scale powered rotorcraft model simulating forward flight. The aerodynamic mechanisms that make these reductions, in both the drag and the download, possible were examined in detail through the use of the measured surface pressure distribution on the fuselage, velocity field measurements made in the wake directly behind the ramp of the fuselage and computational simulations. The fuselage tested was the ROBIN-mod7, which was equipped with a series of eight slots located on the ramp section through which flow control excitation was introduced. These slots were arranged in a U-shaped pattern located slightly downstream of the baseline separation line and parallel to it. The flow control excitation took the form of either synthetic jets, also known as zero-net-mass-flux blowing, and steady blowing. The same set of slots were used for both types of excitation. The differences between the two excitation types and between flow control excitation from different combinations of slots were examined. The flow control is shown to alter the size of the wake and its trajectory relative to the ramp and the tailboom and it is these changes to the wake that result in a reduction in the aerodynamic load.

  5. Rationale, principles and experimental evaluation of the concept of soft stabilization.

    PubMed

    Mulholland, Robert C; Sengupta, Dilip K

    2002-10-01

    The apparent clinical success of spinal stabilization methods that restrict rather than abolish movement in relieving mechanical back pain indicates that the concept of the aetiology of back pain should be reviewed. Further understanding of how degeneration affects disc biomechanics, and an understanding of how current soft stabilization systems alters them, may allow us to define more precisely what are the essential requirements of an ideal soft stabilization system. It appears that abnormal patterns of loading rather than abnormal movement are the reason that disc degeneration causes back pain in some patients. Abnormal load transmission is the principal cause of pain in osteoarthritic joints, and both osteotomy and, indeed, joint replacement succeed because they alter the load transmission across the joint. This concept is supported by the fact that abnormal patterns of stress distribution measured across the disc correlate with painful discs on discography. Clinically, it is often noted that back pain is primarily related to position or posture, rather than movement of the lumbar spine. Clinical success after solid fusion is unpredictable because it does not necessarily prevent painful loading across the disc, and also it may interfere with maintenance of sagittal balance in varying postures. The Graf ligament restricted flexion, and was modestly successful. It unfortunately increased the load over the posterior annulus. The Dynesys system reduces movement both in flexion and extension, and appears to be more successful. However, often it also unloads the disc to a degree that is unpredictable. The authors believe that this unloading of the disc is an important feature of a flexible stabilization system. A new a design of a flexible stabilization system has recently been described in an in vitro study, which unloads the disc by introduction of a load-sharing fulcrum near the axis of movement together with an elastic posterior ligament. This design produces maximal unloading of the disc, whilst allowing a restricted range of movement, which serves the important purpose of allowing the patient to maintain sagittal balance in varying postures.

  6. Couplings of watersheds and coastal waters: Sources and consequences of nutrient enrichment in Waquoit Bay, Massachusetts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valiela, I.; Foreman, K.; LaMontagne, M.

    1992-12-01

    Human activities on coastal watersheds provide the major sources of nutrients entering shallow coastal ecosystems. Nutrient loadings from watersheds alter structure and function of receiving aquatic ecosystems. To investigate this coupling of land to marine systems, a series of subwatersheds of Waquoit Bay differing in degree of urbanization and with widely different nutrient loading rates was studied. The subwatersheds differ in septic tanks numbers and forest acreage. Ground water is the major mechanism that transports nutrients to coastal waters. Some attenuation of nutrient concentrations within the aquifer or at the sediment-water interface, but significant increases in the nutrient content ofmore » groundwater arriving at the shore's edge are in urbanized areas. The groundwater flows through the sediment-water boundary, and sufficient groundwater-borne nutrients (nitrogen in particular) traverse the sediment-water boundary to cause significant changes in the aquatic ecosystem. These loading-dependent alterations include increased nutrients in water, greater primary production by phytoplankton, and increased macroalgal biomass and growth. The increased macroalgal biomass dominates the bay ecosystem through second- or third-order effects such as alterations of nutrient status of water columns and increasing frequency of anoxic events. The increases in seaweeds have decreased the areas covered by eelgrass habitats. The change in habitat type, plus the increased frequency of anoxic events, change the composition of the benthic fauna. The importance of bottom-up control in shallow coastal food webs is evident. The coupling of land to sea by groundwater-borne nutrient transport is mediated by a complex series of steps, making it unlikely to find a one-to-one relation between land use and conditions in the aquatic ecosystem. Appropriate models may provide a way to deal with the complexities of the coupling. 22 refs., 14 figs., 5 tabs.« less

  7. Effect of impeded medial longitudinal arch drop on vertical ground reaction force and center of pressure during static loading.

    PubMed

    Chen, Shing-Jye; Gielo-Perczak, Krystyna

    2011-01-01

    Arch supports commonly used to alleviate foot pain can impede the normal drop of medial longitudinal arch (MLA) thereby altering its function. The purpose of the study was to examine the effect of using arch supports on vertical ground reaction force (GRF) and center of pressure (COP) during simulated midstance while the foot was statically loaded. Ten healthy young subjects were recruited. Two dimensional (2D) analysis of the MLA was captured for both barefoot (BF) and arch support conditions before and after loading via a custom made weight loading apparatus. The foot was loaded and positioned to simulate the midstance phase of walking. Two-dimensional reflective markers demarcated the MLA and captured with the loaded foot on a force platform. The impeded MLA drop was compared between the unloaded BF, loaded BF and loaded arch support conditions. The vertical GRF, the anterior-posterior and the medial-lateral COP displacements were also measured in response to the impeded MLA by the arch supports. The arch supports impeded the MLA drop (p<0.05) and shifted the COP toward the medial side (p<0.05), specifically for the rearfoot (calcaneal segment region), but no changes were determined for the vertical GRF (p>0.05). The impedance of MLA drop by the arch support altered the pattern of the ML COP shift in the rearfoot region. The use of arch supports may not relieve painful foot conditions that are associated with excessive calcaneal eversion indicated by altering COP shifts in localized foot regions.

  8. Treadmill Exercise Improves Fracture Toughness and Indentation Modulus without Altering the Nanoscale Morphology of Collagen in Mice.

    PubMed

    Hammond, Max A; Laine, Tyler J; Berman, Alycia G; Wallace, Joseph M

    The specifics of how the nanoscale properties of collagen (e.g., the crosslinking profile) affect the mechanical integrity of bone at larger length scales is poorly understood despite growing evidence that collagen's nanoscale properties are altered with disease. Additionally, mass independent increases in postyield displacement due to exercise suggest loading-induced improvements in bone quality associated with collagen. To test whether disease-induced reductions in bone quality driven by alterations in collagen can be rescued or prevented via exercise-mediated changes to collagen's nanoscale morphology and mechanical properties, the effects of treadmill exercise and β-aminopropionitrile treatment were investigated. Eight week old female C57BL/6 mice were given a daily subcutaneous injection of either 164 mg/kg β-aminopropionitrile or phosphate buffered saline while experiencing either normal cage activity or 30 min of treadmill exercise for 21 consecutive days. Despite differences in D-spacing distribution (P = 0.003) and increased cortical area (tibial: P = 0.005 and femoral: P = 0.015) due to β-aminopropionitrile treatment, an overt mechanical disease state was not achieved as there were no differences in fracture toughness or 4 point bending due to β-aminopropionitrile treatment. While exercise did not alter (P = 0.058) the D-spacing distribution of collagen or prevent (P < 0.001) the β-aminopropionitrile-induced changes present in the unexercised animals, there were differential effects in the distribution of the reduced elastic modulus due to exercise between control and β-aminopropionitrile-treated animals (P < 0.001). Fracture toughness was increased (P = 0.043) as a main effect of exercise, but no significant differences due to exercise were observed using 4 point bending. Future studies should examine the potential for sex specific differences in the dose of β-aminopropionitrile required to induce mechanical effects in mice and the contributions of other nanoscale aspects of bone (e.g., the mineral-collagen interface) to elucidate the mechanism for the exercise-based improvements in fracture toughness observed here and the increased postyield deformation observed in other studies.

  9. Mechanical load induces sarcoplasmic wounding and FGF release in differentiated human skeletal muscle cultures

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Feeback, D. L.

    1996-01-01

    The transduction mechanism (or mechanisms) responsible for converting a mechanical load into a skeletal muscle growth response are unclear. In this study we have used a mechanically active tissue culture model of differentiated human skeletal muscle cells to investigate the relationship between mechanical load, sarcolemma wounding, fibroblast growth factor release, and skeletal muscle cell growth. Using the Flexcell Strain Unit we demonstrate that as mechanical load increases, so too does the amount of sarcolemma wounding. A similar relationship was also observed between the level of mechanical load inflicted on the cells and the amount of bFGF (FGF2) released into the surrounding medium. In addition, we demonstrate that the muscle cell growth response induced by chronic mechanical loading in culture can be inhibited by the presence of an antibody capable of neutralizing the biological activity of FGF. This study provides direct evidence that mechanically induced, sarcolemma wound-mediated FGF release is an important autocrine mechanism for transducing the stimulus of mechanical load into a skeletal muscle growth response.

  10. MSC/NASTRAN DMAP Alter Used for Closed-Form Static Analysis With Inertia Relief and Displacement-Dependent Loads

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Solving for the displacements of free-free coupled systems acted upon by static loads is a common task in the aerospace industry. Often, these problems are solved by static analysis with inertia relief. This technique allows for a free-free static analysis by balancing the applied loads with the inertia loads generated by the applied loads. For some engineering applications, the displacements of the free-free coupled system induce additional static loads. Hence, the applied loads are equal to the original loads plus the displacement-dependent loads. A launch vehicle being acted upon by an aerodynamic loading can have such applied loads. The final displacements of such systems are commonly determined with iterative solution techniques. Unfortunately, these techniques can be time consuming and labor intensive. Because the coupled system equations for free-free systems with displacement-dependent loads can be written in closed form, it is advantageous to solve for the displacements in this manner. Implementing closed-form equations in static analysis with inertia relief is analogous to implementing transfer functions in dynamic analysis. An MSC/NASTRAN (MacNeal-Schwendler Corporation/NASA Structural Analysis) DMAP (Direct Matrix Abstraction Program) Alter was used to include displacement-dependent loads in static analysis with inertia relief. It efficiently solved a common aerospace problem that typically has been solved with an iterative technique.

  11. The stress distribution in pin-loaded orthotropic plates

    NASA Technical Reports Server (NTRS)

    Klang, E. C.; Hyer, M. W.

    1985-01-01

    The performance of mechanically fastened composite joints was studied. Specially, a single-bolt connector was modeled as a pin-loaded, infinite plate. The model that was developed used two dimensional, complex variable, elasticity techniques combined with a boundary collocation procedure to produce solutions for the problem. Through iteration, the boundary conditions were satisfied and the stresses in the plate were calculated. Several graphite epoxy laminates were studied. In addition, parameters such as the pin modulus, coefficient of friction, and pin-plate clearance were varied. Conclusions drawn from this study indicate: (1) the material properties (i.e., laminate configuration) of the plate alter the stress state and, for highly orthotropic materials, the contact stress deviates greatly from the cosinusoidal distribution often assumed; (2) friction plays a major role in the distribution of stresses in the plate; (3) reversing the load direction also greatly effects the stress distribution in the plate; (4) clearance (or interference) fits change the contact angle and thus the location of the peak hoop stress; and (5) a rigid pin appears to be a good assumption for typical material systems.

  12. Relationship between locking-bolt torque and load pre-tension in the Ilizarov frame.

    PubMed

    Osei, N A; Bradley, B M; Culpan, P; Mitchell, J B; Barry, M; Tanner, K E

    2006-10-01

    The wire-bolt interface in an Ilizarov frame has been mechanically tested. The optimal torque to be applied to the frame locking-bolts during physiological loading has been defined. The set-up configuration was as is used clinically except a copper tube was used to simulate bone. The force-displacement curves of the Ilizarov wires are not altered by locking-bolt torque. The force in the bone model at which pre-tension is lost increases as the locking-bolts are tightened to 14 Nm torque, but decreases if torque exceeds 14 Nm. Thus, 14 Nm is the optimal locking-bolt torque in frame. The relationship between pre-tension versus load for different locking-bolt torques arises because at low and high clamping torques poor wire holding and plastic deformation respectively occur. Wire damage was seen under light and electron microscopy. Clinically, over or under-tightening locking-bolts will cause loss of pre-tension, reduction in frame stiffness and excessive movement at the fracture site, which may be associated with delayed union.

  13. Effect of high loading on substrate utilization kinetics and microbial community structure in super fast submerged membrane bioreactor.

    PubMed

    Sözen, S; Çokgör, E U; Başaran, S Teksoy; Aysel, M; Akarsubaşı, A; Ergal, I; Kurt, H; Pala-Ozkok, I; Orhon, D

    2014-05-01

    The study investigated the effect of high substrate loading on substrate utilization kinetics, and changes inflicted on the composition of the microbial community in a superfast submerged membrane bioreactor. Submerged MBR was sequentially fed with a substrate mixture and acetate; its performance was monitored at steady-state, at extremely low sludge age values of 2.0, 1.0 and 0.5d, all adjusted to a single hydraulic retention time of 8.0 h. Each MBR run was repeated when substrate feeding was increased from 200 mg COD/L to 1000 mg COD/L. Substrate utilization kinetics was altered to significantly lower levels when the MBR was adjusted to higher substrate loadings. Molecular analysis of the biomass revealed that variable process kinetics could be correlated with parallel changes in the composition of the microbial community, mainly by a replacement mechanism, where newer species, better adapted to the new growth conditions, substituted others that are washed out from the system. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Processing Capacity under Perceptual and Cognitive Load: A Closer Look at Load Theory

    ERIC Educational Resources Information Center

    Fitousi, Daniel; Wenger, Michael J.

    2011-01-01

    Variations in perceptual and cognitive demands (load) play a major role in determining the efficiency of selective attention. According to load theory (Lavie, Hirst, Fockert, & Viding, 2004) these factors (a) improve or hamper selectivity by altering the way resources (e.g., processing capacity) are allocated, and (b) tap resources rather than…

  15. Nutrients structure changes impact the competition and succession between diatom and dinoflagellate in the East China Sea.

    PubMed

    Zhou, Yuping; Zhang, Yanmin; Li, Fangfang; Tan, Liju; Wang, Jiangtao

    2017-01-01

    Nutrients variations caused by anthropogenic activities alter phytoplankton community interactions, especially competition and succession between two algal species. East China Sea experiences annual successions of Skeletonema costatum and Prorocentrum donghaiense and large-scale blooms of P. donghaiense. In this study, the growth and competition responses of S. costatum and P. donghaiense to different inorganic nutrients structure were evaluated through field and indoors experiments to further understand the nutrients mechanism of these events. Results showed that low Si/N ratio (Si/N<1) and high N/P (>50) possibly accelerated P. donghaiense outbreak and decreased Si/N caused by low Si concentration could speed up S. costatum decay. Excessive DIN also accelerated blooms dominated by P. donghaiense (D t up to -3) when S. costatum perished. Increased DIN loads from anthropogenic activities were possibly responsible for the changes in phytoplankton communities and dinoflagellate outbreak when Si concentration decreased as a result of governmental control efforts. With effective management practices for Si and P reductions worldwide, managers should be aware of the negative implications of unsuccessful management of system N loading because N may significantly alter the composition and ecosystem of phytoplankton communities. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Midsole material-related force control during heel-toe running.

    PubMed

    Kersting, Uwe G; Brüggemann, Gert-Peter

    2006-01-01

    The impact maximum and rearfoot eversion have been used as indicators of load on internal structures in running. The midsole hardness of a typical running shoe was varied systematically to determine the relationship between external ground reaction force (GRF), in-shoe force, and kinematic variables. Eight subjects were tested during overground running at 4 m/s. Rearfoot movement as well as in-shoe forces and external GRF varied nonsystematically with midsole hardness. Kinematic parameters such as knee flexion and foot velocity at touchdown (TD), also varied nonsystematically with altered midsole hardness. Results demonstrate that considerable variations of in-shoe loading occur that were not depicted by external GRF measurements alone. Individuals apparently use different strategies of mechanical and neuromuscular adaptation in response to footwear modifications. In conclusion, shoe design effects on impact forces or other factors relating to injuries depend on the individual and therefore cannot be generalized.

  17. Connective tissue responses to some heavy metals. II. Lead: histology and ultrastructure.

    PubMed Central

    Ellender, G.; Ham, K. N.

    1987-01-01

    Lead loaded ion exchange resin beads implanted into the loose connective tissue of the rat pinna induced local lesions which differed widely from those of the control (sodium loaded) beads (Ellender & Ham 1987). These lesions were characterized by changes in the granulation tissue and the approximating connective tissue. Granulation tissue contained mononuclear phagocytes in various guises, and some cells with intranuclear inclusion bodies. The matrix of the granulation tissue contained collagen fibrils having a wide range of diameters suggestive of altered collagen biosynthesis. Foci of collagen mineralization occurred in zones of combined trauma and lead impregnation. Once mineralized they became enveloped by giant cells and epithelioid cells. Lead in damaged tissues is thought to modify the protective mechanism of calcification inhibition and the biosynthesis of the matrix. Images Fig. 6 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:3040063

  18. Attentional load and sensory competition in human vision: modulation of fMRI responses by load at fixation during task-irrelevant stimulation in the peripheral visual field.

    PubMed

    Schwartz, Sophie; Vuilleumier, Patrik; Hutton, Chloe; Maravita, Angelo; Dolan, Raymond J; Driver, Jon

    2005-06-01

    Perceptual suppression of distractors may depend on both endogenous and exogenous factors, such as attentional load of the current task and sensory competition among simultaneous stimuli, respectively. We used functional magnetic resonance imaging (fMRI) to compare these two types of attentional effects and examine how they may interact in the human brain. We varied the attentional load of a visual monitoring task performed on a rapid stream at central fixation without altering the central stimuli themselves, while measuring the impact on fMRI responses to task-irrelevant peripheral checkerboards presented either unilaterally or bilaterally. Activations in visual cortex for irrelevant peripheral stimulation decreased with increasing attentional load at fixation. This relative decrease was present even in V1, but became larger for successive visual areas through to V4. Decreases in activation for contralateral peripheral checkerboards due to higher central load were more pronounced within retinotopic cortex corresponding to 'inner' peripheral locations relatively near the central targets than for more eccentric 'outer' locations, demonstrating a predominant suppression of nearby surround rather than strict 'tunnel vision' during higher task load at central fixation. Contralateral activations for peripheral stimulation in one hemifield were reduced by competition with concurrent stimulation in the other hemifield only in inferior parietal cortex, not in retinotopic areas of occipital visual cortex. In addition, central attentional load interacted with competition due to bilateral versus unilateral peripheral stimuli specifically in posterior parietal and fusiform regions. These results reveal that task-dependent attentional load, and interhemifield stimulus-competition, can produce distinct influences on the neural responses to peripheral visual stimuli within the human visual system. These distinct mechanisms in selective visual processing may be integrated within posterior parietal areas, rather than earlier occipital cortex.

  19. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kanno, Ayumi, E-mail: akanno@med.kobe-u.ac.jp; Asahara, Shun-ichiro, E-mail: asahara@med.kobe-u.ac.jp; Masuda, Katsuhisa, E-mail: katsuhisa.m.0707@gmail.com

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage ofmore » insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.« less

  20. Metabolic activity, experiment M171. [space flight effects on human metabolism

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.

    1973-01-01

    The Skylab metabolic activity experiment determines if man's metabolic effectiveness in doing mechanical work is progressively altered by a simulated Skylab environment, including environmental factors such as slightly increased pCO2. This test identified several hardware/procedural anomalies. The most important of these were: (1) the metabolic analyzer measured carbon dioxide production and expired water too high; (2) the ergometer load module failed under continuous high workload conditions; (3) a higher than desirable number of erroneous blood pressure measurements were recorded; (4) vital capacity measurements were unreliable; and (5) anticipated crew personal exercise needs to be more structured.

  1. Chest Wall Diseases: Respiratory Pathophysiology.

    PubMed

    Tzelepis, George E

    2018-06-01

    The chest wall consists of various structures that function in an integrated fashion to ventilate the lungs. Disorders affecting the bony structures or soft tissues of the chest wall may impose elastic loads by stiffening the chest wall and decreasing respiratory system compliance. These alterations increase the work of breathing and lead to hypoventilation and hypercapnia. Respiratory failure may occur acutely or after a variable period of time. This review focuses on the pathophysiology of respiratory function in specific diseases and disorders of the chest wall, and highlights pathogenic mechanisms of respiratory failure. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Cardiovascular function in space flight

    NASA Technical Reports Server (NTRS)

    Nicogossian, A. E.; Charles, J. B.; Bungo, M. W.; Leach-Huntoon, C. S.

    1990-01-01

    Postflight orthostatic intolerance and cardiac hemodynamics associated with manned space flight have been investigated on seven STS missions. Orthostatic heart rates appear to be influenced by the mission duration. The rates increase during the first 7-10 days of flight and recover partially after that. Fluid loading is used as a countermeasure to the postflight orthostatic intolerance. The carotid baroreceptor function shows only slight responsiveness to orthostatic stimulation. Plots of the baroreceptor function are presented. It is concluded that an early adaptation to the space flight conditions involves a fluid shift and that the subsequent alterations in the neutral controlling mechanisms contribute to the orthoststic intolerance.

  3. Sex speeds adaptation by altering the dynamics of molecular evolution.

    PubMed

    McDonald, Michael J; Rice, Daniel P; Desai, Michael M

    2016-03-10

    Sex and recombination are pervasive throughout nature despite their substantial costs. Understanding the evolutionary forces that maintain these phenomena is a central challenge in biology. One longstanding hypothesis argues that sex is beneficial because recombination speeds adaptation. Theory has proposed several distinct population genetic mechanisms that could underlie this advantage. For example, sex can promote the fixation of beneficial mutations either by alleviating interference competition (the Fisher-Muller effect) or by separating them from deleterious load (the ruby in the rubbish effect). Previous experiments confirm that sex can increase the rate of adaptation, but these studies did not observe the evolutionary dynamics that drive this effect at the genomic level. Here we present the first, to our knowledge, comparison between the sequence-level dynamics of adaptation in experimental sexual and asexual Saccharomyces cerevisiae populations, which allows us to identify the specific mechanisms by which sex speeds adaptation. We find that sex alters the molecular signatures of evolution by changing the spectrum of mutations that fix, and confirm theoretical predictions that it does so by alleviating clonal interference. We also show that substantially deleterious mutations hitchhike to fixation in adapting asexual populations. In contrast, recombination prevents such mutations from fixing. Our results demonstrate that sex both speeds adaptation and alters its molecular signature by allowing natural selection to more efficiently sort beneficial from deleterious mutations.

  4. A method for determination of equine hoof strain patterns using photoelasticity: an in vitro study.

    PubMed

    Dejardin, L M; Arnoczky, S P; Cloud, G L

    1999-05-01

    During impact, equine hooves undergo viscoelastic deformations which may result in potentially harmful strains. Previous hoof strain studies using strain gauges have been inconclusive due to arbitrary gauge placement. Photoelastic stress analysis (PSA) is a full-field technique which visually displays strains over entire loaded surfaces. This in vitro study identifies normal hoof strain patterns using PSA. Custom-made photoelastic plastic sheets were applied to the hoof surface. The hooves were axially loaded (225 kg) under level and varus/valgus conditions. Strain patterns were video-recorded through a polariscope. Strains were concentrated between middle and distal thirds of the hoof wall regardless of the loading conditions. This strain distribution appears to result from the differential expansion of the hoof wall under load. Increasing load resulted in higher strains and asymmetric loading resulted in an ipsilateral increase in strain magnitudes without altering strain locations. This study shows that PSA is a reliable method with which to evaluate hoof strains in vitro and is sensitive enough to reflect subtle load-related strain alterations.

  5. Alzheimer's Disease: The Role of Microglia in Brain Homeostasis and Proteopathy

    PubMed Central

    Clayton, Kevin A.; Van Enoo, Alicia A.; Ikezu, Tsuneya

    2017-01-01

    Brain aging is central to late-onset Alzheimer's disease (LOAD), although the mechanisms by which it occurs at protein or cellular levels are not fully understood. Alzheimer's disease is the most common proteopathy and is characterized by two unique pathologies: senile plaques and neurofibrillary tangles, the former accumulating earlier than the latter. Aging alters the proteostasis of amyloid-β peptides and microtubule-associated protein tau, which are regulated in both autonomous and non-autonomous manners. Microglia, the resident phagocytes of the central nervous system, play a major role in the non-autonomous clearance of protein aggregates. Their function is significantly altered by aging and neurodegeneration. This is genetically supported by the association of microglia-specific genes, TREM2 and CD33, and late onset Alzheimer's disease. Here, we propose that the functional characterization of microglia, and their contribution to proteopathy, will lead to a new therapeutic direction in Alzheimer's disease research. PMID:29311768

  6. The Pivotal Role of Airway Smooth Muscle in Asthma Pathophysiology

    PubMed Central

    Ozier, Annaïg; Allard, Benoit; Bara, Imane; Girodet, Pierre-Olivier; Trian, Thomas; Marthan, Roger; Berger, Patrick

    2011-01-01

    Asthma is characterized by the association of airway hyperresponsiveness (AHR), inflammation, and remodelling. The aim of the present article is to review the pivotal role of airway smooth muscle (ASM) in the pathophysiology of asthma. ASM is the main effector of AHR. The mechanisms of AHR in asthma may involve a larger release of contractile mediators and/or a lower release of relaxant mediators, an improved ASM cell excitation/contraction coupling, and/or an alteration in the contraction/load coupling. Beyond its contractile function, ASM is also involved in bronchial inflammation and remodelling. Whereas ASM is a target of the inflammatory process, it can also display proinflammatory and immunomodulatory functions, through its synthetic properties and the expression of a wide range of cell surface molecules. ASM remodelling represents a key feature of asthmatic bronchial remodelling. ASM also plays a role in promoting complementary airway structural alterations, in particular by its synthetic function. PMID:22220184

  7. Structural analysis of two different stent configurations.

    PubMed

    Simão, M; Ferreira, J M; Mora-Rodriguez, J; Ramos, H M

    2017-06-01

    Two different stent configurations (i.e. the well known Palmaz-Schatz (PS) and a new stent configuration) are mechanically investigated. A finite element model was used to study the two geometries under combining loads and a computational fluid dynamic model based on fluid structure interaction was developed investigating the plaque and the artery wall reactions in a stented arterial segment. These models determine the stress and displacement fields of the two stents under internal pressure conditions. Results suggested that stent designs cause alterations in vascular anatomy that adversely affect arterial stress distributions within the wall, which have impact in the vessel responses such as the restenosis. The hemodynamic analysis shows the use of new stent geometry suggests better biofluid mechanical response such as the deformation and the progressive amount of plaque growth.

  8. A role for intracellular zinc in glioma alteration of neuronal chloride equilibrium

    PubMed Central

    Di Angelantonio, S; Murana, E; Cocco, S; Scala, F; Bertollini, C; Molinari, M G; Lauro, C; Bregestovski, P; Limatola, C; Ragozzino, D

    2014-01-01

    Glioma patients commonly suffer from epileptic seizures. However, the mechanisms of glioma-associated epilepsy are far to be completely understood. Using glioma-neurons co-cultures, we found that tumor cells are able to deeply influence neuronal chloride homeostasis, by depolarizing the reversal potential of γ-aminobutyric acid (GABA)-evoked currents (EGABA). EGABA depolarizing shift is due to zinc-dependent reduction of neuronal KCC2 activity and requires glutamate release from glioma cells. Consistently, intracellular zinc loading rapidly depolarizes EGABA in mouse hippocampal neurons, through the Src/Trk pathway and this effect is promptly reverted upon zinc chelation. This study provides a possible molecular mechanism linking glioma invasion to excitation/inhibition imbalance and epileptic seizures, through the zinc–mediated disruption of neuronal chloride homeostasis. PMID:25356870

  9. Fruit load governs transpiration of olive trees.

    PubMed

    Bustan, Amnon; Dag, Arnon; Yermiyahu, Uri; Erel, Ran; Presnov, Eugene; Agam, Nurit; Kool, Dilia; Iwema, Joost; Zipori, Isaac; Ben-Gal, Alon

    2016-03-01

    We tested the hypothesis that whole-tree water consumption of olives (Olea europaea L.) is fruit load-dependent and investigated the driving physiological mechanisms. Fruit load was manipulated in mature olives grown in weighing-drainage lysimeters. Fruit was thinned or entirely removed from trees at three separate stages of growth: early, mid and late in the season. Tree-scale transpiration, calculated from lysimeter water balance, was found to be a function of fruit load, canopy size and weather conditions. Fruit removal caused an immediate decline in water consumption, measured as whole-plant transpiration normalized to tree size, which persisted until the end of the season. The later the execution of fruit removal, the greater was the response. The amount of water transpired by a fruit-loaded tree was found to be roughly 30% greater than that of an equivalent low- or nonyielding tree. The tree-scale response to fruit was reflected in stem water potential but was not mirrored in leaf-scale physiological measurements of stomatal conductance or photosynthesis. Trees with low or no fruit load had higher vegetative growth rates. However, no significant difference was observed in the overall aboveground dry biomass among groups, when fruit was included. This case, where carbon sources and sinks were both not limiting, suggests that the role of fruit on water consumption involves signaling and alterations in hydraulic properties of vascular tissues and tree organs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Characterizing Knee Loading Asymmetry in Individuals Following Anterior Cruciate Ligament Reconstruction Using Inertial Sensors

    PubMed Central

    Sigward, Susan M.; Chan, Ming-Sheng M.; Lin, Paige E.

    2016-01-01

    Limitations in the ability to identify knee extensor loading deficits during gait in individuals following anterior cruciate ligament reconstruction (ACLr) may underlie their persistence. A recent study suggested that shank angular velocity, directly output from inertial sensors, differed during gait between individuals post-ACLr and controls. However, it is not clear if this kinematic variable relates to knee moments calculated using joint kinematics and ground reaction forces. Heel rocker mechanics during loading response of gait, characterized by rapid shank rotation, require knee extensor control. Measures of shank angular velocity may be reflective of knee moments. This study investigated the relationship between shank angular velocity and knee extensor moment during gait in individuals (n=19) 96.7±16.8 days post-ACLr. Gait was assessed concurrently using inertial sensors and a marker-based motion system with force platforms. Peak angular velocity and knee extensor moment were strongly correlated (r=0.75, p<0.001) and between limb ratios of angular velocity predicted between limb ratios of extensor moment (r2=0.57 ,p<0.001) in the absence of between limb differences in spatiotemporal gait parameters. The strength of these relationships indicate that shank kinematic data offer meaningful information regarding knee loading and provide a potential alternative to full motion analysis systems for identification of altered knee loading following ACLr PMID:27395452

  11. The MCK mouse heart model of Friedreich's ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation

    PubMed Central

    Whitnall, Megan; Rahmanto, Yohan Suryo; Sutak, Robert; Xu, Xiangcong; Becker, Erika M.; Mikhael, Marc R.; Ponka, Prem; Richardson, Des R.

    2008-01-01

    There is no effective treatment for the cardiomyopathy of the most common autosomal recessive ataxia, Friedreich's ataxia (FA). The identification of potentially toxic mitochondrial (MIT) iron (Fe) deposits in FA suggests that Fe plays a role in its pathogenesis. This study used the muscle creatine kinase conditional frataxin (Fxn) knockout (mutant) mouse model that reproduces the classical traits associated with cardiomyopathy in FA. We examined the mechanisms responsible for the increased cardiac MIT Fe loading in mutants. Moreover, we explored the effect of Fe chelation on the pathogenesis of the cardiomyopathy. Our investigation showed that increased MIT Fe in the myocardium of mutants was due to marked transferrin Fe uptake, which was the result of enhanced transferrin receptor 1 expression. In contrast to the mitochondrion, cytosolic ferritin expression and the proportion of cytosolic Fe were decreased in mutant mice, indicating cytosolic Fe deprivation and markedly increased MIT Fe targeting. These studies demonstrated that loss of Fxn alters cardiac Fe metabolism due to pronounced changes in Fe trafficking away from the cytosol to the mitochondrion. Further work showed that combining the MIT-permeable ligand pyridoxal isonicotinoyl hydrazone with the hydrophilic chelator desferrioxamine prevented cardiac Fe loading and limited cardiac hypertrophy in mutants but did not lead to overt cardiac Fe depletion or toxicity. Fe chelation did not prevent decreased succinate dehydrogenase expression in the mutants or loss of cardiac function. In summary, we show that loss of Fxn markedly alters cellular Fe trafficking and that Fe chelation limits myocardial hypertrophy in the mutant. PMID:18621680

  12. The CENP-A N-Tail Confers Epigenetic Stability to Centromeres via the CENP-T Branch of the CCAN in Fission Yeast

    PubMed Central

    Folco, H. Diego; Campbell, Christopher S.; May, Karen M.; Espinoza, Celso A.; Oegema, Karen; Hardwick, Kevin G.; Grewal, Shiv I. S.; Desai, Arshad

    2014-01-01

    Summary In most eukaryotes, centromeres are defined epigenetically by presence of the histone H3 variant CENP-A [1-3]. CENP-A containing chromatin recruits the constitutive centromere-associated network (CCAN) of proteins, which in turn directs assembly of the outer kinetochore to form microtubule attachments and ensure chromosome segregation fidelity [4-6]. While the mechanisms that load CENP-A at centromeres are being elucidated, the functions of its divergent N-terminal tail remain enigmatic [7-12]. Here, we employ the well-studied fission yeast centromere [13-16] to investigate the function of the CENP-A (Cnp1) N-tail. We show that alteration of the N-tail did not affect Cnp1 loading at centromeres, outer kinetochore formation, or spindle checkpoint signaling, but nevertheless elevated chromosome loss. N-Tail mutants exhibited synthetic lethality with an altered centromeric DNA sequence, with rare survivors harboring chromosomal fusions in which the altered centromere was epigenetically inactivated. Elevated centromere inactivation was also observed for N-tail mutants with unaltered centromeric DNA sequences. N-tail mutants specifically reduced localization of the CCAN proteins Cnp20/CENP-T and Mis6/CENP-I, but not Cnp3/CENP-C. Overexpression of Cnp20/CENP-T suppressed defects in an N-tail mutant, suggesting a link between reduced CENP-T recruitment and the observed centromere inactivation phenotype. Thus, the Cnp1 N-tail promotes epigenetic stability of centromeres in fission yeast, at least in part via recruitment of the CENP-T branch of the CCAN. PMID:25619765

  13. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

    PubMed

    Proitsi, Petroula; Lupton, Michelle K; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F

    2014-09-01

    Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary.

  14. Composite Grids for Reinforcement of Concrete Structures.

    DTIC Science & Technology

    1998-06-01

    to greater compressive loads before induced shear failure occurs. Concrete columns were tested in compression to explore alter- native... columns were tested on the same day as the fiber-reinforced concrete columns . Load /deflection readings were taken with the load cell to determine the...ln) Figure 78. Ultimate load vs toughness for the different beam types tested . USACERLTR-98/81 141 £\\

  15. Preliminary analysis of the bio-mechanical characteristics for High-kitchen Municipal Solid Waste

    NASA Astrophysics Data System (ADS)

    Li, He; Zhang, Jian Guo; Lan, Ji Wu; He, Haijie

    2017-11-01

    Degradation of Municipal Solid Wastes (MSW) results in a change in solid skeleton, particle size and pore structure, inducing an alteration of compressibility and liquid/gas conductivity of the wastes. To investigate the complicated biological, hydraulic and mechanical coupled processes of the MSWs, a pilot-scale experimental device which is consist of waste column container, environment regulation system, vertical loading system and measuring system for liquid/gas conductivity is built. With the experimental systems, long-term tests were set up to investigate the biological, hydraulic and mechanical behaviour of the High-kitchen Municipal solid waste with high organic content and high water content. Different values of vertical stress and different degradation conditions (micro-aerobic and anaerobic) were simulated. Throughout the experiments, the changes in total volume, degree of saturation, leachate quantity and chemistry, LFG generation and composition, liquid and gas conductivity were measured. The experimental results will provide solid data for a development of the Bio-Hydro-Mechanical coupled characteristics for High-kitchen Municipal solid waste.

  16. Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action

    PubMed Central

    Fonseca-Silva, Fernanda; Inacio, Job D. F.; Canto-Cavalheiro, Marilene M.; Menna-Barreto, Rubem F. S.; Almeida-Amaral, Elmo E.

    2016-01-01

    Background The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. Methodology/Principal Finding Apigenin reduced the infection index in a dose-dependent manner, with IC50 values of 4.3 μM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. Conclusions/Significance In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports further studies of apigenin as a candidate for the chemotherapeutic treatment of leishmaniasis. PMID:26862901

  17. The resistance of cortical bone tissue to failure under cyclic loading is reduced with alendronate.

    PubMed

    Bajaj, Devendra; Geissler, Joseph R; Allen, Matthew R; Burr, David B; Fritton, J C

    2014-07-01

    Bisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality

    PubMed Central

    2011-01-01

    Background Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Methods Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Results Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. Conclusions A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health. PMID:21529374

  19. Causal assessment of dietary acid load and bone disease: a systematic review & meta-analysis applying Hill's epidemiologic criteria for causality.

    PubMed

    Fenton, Tanis R; Tough, Suzanne C; Lyon, Andrew W; Eliasziw, Misha; Hanley, David A

    2011-04-30

    Modern diets have been suggested to increase systemic acid load and net acid excretion. In response, alkaline diets and products are marketed to avoid or counteract this acid, help the body regulate its pH to prevent and cure disease. The objective of this systematic review was to evaluate causal relationships between dietary acid load and osteoporosis using Hill's criteria. Systematic review and meta-analysis. We systematically searched published literature for randomized intervention trials, prospective cohort studies, and meta-analyses of the acid-ash or acid-base diet hypothesis with bone-related outcomes, in which the diet acid load was altered, or an alkaline diet or alkaline salts were provided, to healthy human adults. Cellular mechanism studies were also systematically examined. Fifty-five of 238 studies met the inclusion criteria: 22 randomized interventions, 2 meta-analyses, and 11 prospective observational studies of bone health outcomes including: urine calcium excretion, calcium balance or retention, changes of bone mineral density, or fractures, among healthy adults in which acid and/or alkaline intakes were manipulated or observed through foods or supplements; and 19 in vitro cell studies which examined the hypothesized mechanism. Urine calcium excretion rates were consistent with osteoporosis development; however calcium balance studies did not demonstrate loss of whole body calcium with higher net acid excretion. Several weaknesses regarding the acid-ash hypothesis were uncovered: No intervention studies provided direct evidence of osteoporosis progression (fragility fractures, or bone strength as measured using biopsy). The supporting prospective cohort studies were not controlled regarding important osteoporosis risk factors including: weight loss during follow-up, family history of osteoporosis, baseline bone mineral density, and estrogen status. No study revealed a biologic mechanism functioning at physiological pH. Finally, randomized studies did not provide evidence for an adverse role of phosphate, milk, and grain foods in osteoporosis. A causal association between dietary acid load and osteoporotic bone disease is not supported by evidence and there is no evidence that an alkaline diet is protective of bone health.

  20. Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

    PubMed Central

    Kudalkar, Emily M.; Scarborough, Emily A.; Umbreit, Neil T.; Zelter, Alex; Gestaut, Daniel R.; Riffle, Michael; Johnson, Richard S.; MacCoss, Michael J.; Asbury, Charles L.; Davis, Trisha N.

    2015-01-01

    Multiple protein subcomplexes of the kinetochore cooperate as a cohesive molecular unit that forms load-bearing microtubule attachments that drive mitotic chromosome movements. There is intriguing evidence suggesting that central kinetochore components influence kinetochore–microtubule attachment, but the mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected by an extensive network of contacts, each essential for viability in cells, and collectively able to withstand substantial tensile load. Using a single-molecule approach, we demonstrate that an individual MIND complex enhances the microtubule-binding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex. In addition, MIND activation is redundant with the effects of a mutation in Ndc80 that might alter its ability to adopt a folded conformation. Together, our results suggest a previously unidentified mechanism for regulating microtubule binding of an outer kinetochore component by a central kinetochore complex. PMID:26430240

  1. Effects of Loading Frequency on Fatigue Behavior, Residual Stress, and Microstructure of Deep-Rolled Stainless Steel AISI 304 at Elevated Temperatures

    NASA Astrophysics Data System (ADS)

    Nikitin, I.; Juijerm, P.

    2018-02-01

    The effects of loading frequency on the fatigue behavior of non-deep-rolled (NDR) and deep-rolled (DR) austenitic stainless steel AISI 304 were systematically clarified at elevated temperatures, especially at temperatures exhibiting the dynamic strain aging (DSA) phenomena. Tension-compression fatigue tests were performed isothermally at temperatures of 573 K and 773 K (300 °C and 500 °C) with different loading frequencies of 5, 0.5, 0.05, and 0.005 Hz. For the DR condition, the residual stresses and work-hardening states will be presented. It was found that DSA would be detected at appropriate temperatures and deformation rates. The cyclic deformation curves and the fatigue lives of the investigated austenitic stainless steel AISI 304 are considerably affected by the DSA, especially on the DR condition having high dislocation densities at the surface and in near-surface regions. In the temperature range of the DSA, residual stresses and work-hardening states of the DR condition seem to be stabilized. The microstructural alterations were investigated by transmission electron microscopy (TEM). At an appropriate temperature with low loading frequency, the plastic deformation mechanism shifted from a wavy slip manner to a planar slip manner in the DSA regimes, whereas the dislocation movements were obstructed.

  2. The Use of Altered Gravity as a Tool to Understand Neurovestibular Mechanisms in Vertebrates

    NASA Technical Reports Server (NTRS)

    Boyle, R.; Popova, Y.; Varelas, J.

    2017-01-01

    Vertebrates sense gravito-inertial acceleration by mechanoreceptors (hair cells) in the otolith structures of the inner ear. These structures consist of ciliated sensory hair cells surmounted by biomineral grains of calcium carbonate (CaCO3) called otoconia that provide mechanical loading of hair cell cilia. Changes in their high density can alter the hair cells sensitivity to acceleration and orientation with respect to gravity. A widely considered mechanism by which the animal responds to a chronic change in amplitude of gravity is a change in weight-lending otoconia. Hair cells are synaptically coupled to the vestibular nerve afferents that convey the signals into the brain. Synapses are modifiable in strength and numbers, and thereby can be an additional target to adjust the sensation as the gravity load changes. Here, we present the results obtained in 2 species exposed both to G and HG. Adult toadfish, Opsanus tau, were exposed to G in 2 short-duration shuttle missions and to 1.4 2.24G [resultant] centrifugation for 1-32 days; re-adaptation was studied following 1-8 days after return to 1G. Results show a biphasic pattern in response to 2.24G: initial hypersensitivity, similar to that observed after G exposure, followed by transition to a significant decrease at 16-32 days. Recovery from HG exposure is 4-8 days. Two major pieces of information are still needed: vertebrate hair cell response to altered gravity and impact of longer duration exposures on sensory plasticity. To address the latter we applied electron microscopic techniques to image otoconia mass obtained from 1) mice subjected to 91-days of weightlessness in the Mouse Drawer System (MDS) flown on International Space Station, 2) mice subjected to 91-days of 1.24G centrifugation on ground, and 3) mice flown on 2 short-duration orbital missions. Images indicate a clear restructuring of individual otoconia, suggesting deposition to the outer shell. Images from their HG counterparts indicate the converse - an ablation of the otoconia mass. For shorter duration exposures to weightlessness on 13-day shuttle missions mice otoconia appear normal. Despite the permanence of 1G in evolution the animal senses exposure to a novel, non-1G, environment and adaptive mechanisms are initiated - in the short term compensation is likely confined to the peripheral sensory receptors, the brain or both. For longer exposures structural modifications of the endorgan may also result.

  3. Effects of inorganic phosphate and ADP on calcium handling by the sarcoplasmic reticulum in rat skinned cardiac muscles.

    PubMed

    Xiang, J Z; Kentish, J C

    1995-03-01

    The aim was to investigate whether, and how, increases in inorganic phosphate (Pi) and ADP, similar to those occurring intracellularly during early myocardial ischaemia, affect the calcium handling of the sarcoplasmic reticulum. Rat ventricular trabeculae were permeabilised with saponin. The physiological process of calcium induced calcium release (CICR) from the muscle sarcoplasmic reticulum was triggered via flash photolysis of the "caged Ca2+", nitr-5. Alternatively, calcium release was induced by rapid application of caffeine to give an estimate of sarcoplasmic reticular calcium loading. The initial rate of sarcoplasmic reticular calcium pumping was also assessed by photolysis of caged ATP at saturating [Ca2+]. Myoplasmic [Ca2+] (using fluo-3) and isometric force were measured. Pi (2-20 mM) significantly depressed the magnitude of CICR and the associated force transient. Sarcoplasmic reticular calcium loading was inhibited even more than CICR by Pi, suggesting that reduced calcium loading could account for all of the inhibitory effect of Pi on CICR and that Pi may slightly activate the calcium release mechanism. The reduced sarcoplasmic reticular calcium loading seemed to be due to a fall in the free energy of ATP hydrolysis (delta GATP) available for the calcium pump, since equal decreases in delta GATP produced by adding both Pi and ADP in various ratios caused similar falls in the calcium loading of the sarcoplasmic reticulum. The caged ATP experiments indicated that Pi (20 mM) did not affect the rate constant of sarcoplasmic reticular calcium uptake. ADP (10 mM) alone, or with 1 mM Pi, inhibited calcium loading. In spite of this, ADP (10 mM) did not alter CICR and, when 1 mM Pi was added, ADP increased CICR above control. An increase in intracellular Pi reduces sarcoplasmic reticular calcium loading and thus depresses the CICR. This could be an important contributing factor in the hypoxic or ischaemic contractile failure of the myocardium. However the detrimental effect of Pi may be offset to some extent by a stimulatory action of ADP on the calcium release mechanism of CICR.

  4. Urban Runoff and Nutrients Loading Control from Sustainable BMPs (Invited)

    NASA Astrophysics Data System (ADS)

    Xiao, Q.

    2009-12-01

    Climate change alters hydrodynamic and nutrient dynamic in both large and small geographic scales. These changes in our freshwater system directly affect drinking water, food production, business, and all aspects of our life. Along with climate change is increasing urbanization which alters natural landscape. Urban runoff has been identified as one of many potential drivers of the decline of pelagic fishes in san Francisco Bay-Delta region. Recent found of Pyrethroids in American River has increased scientists, public, and policy makers’ concern about our fresh water system. Increasing our understanding about the fundamental hydrodynamic, nutrient dynamics, and the transport mechanics of runoff and nutrients are important for future water resource and ecosystem management. Urbanization has resulted in significantly increasing the amount of impervious land cover. Most impervious land covers are hydrophobic that alters surface runoff because of the effects on surface retention storage, rainfall interception, and infiltration. Large volumes of excess storm runoff from urbanized areas cause flooding, water pollution, groundwater recharge deficits, destroyed habitat, beach closures, and toxicity to aquatic organisms. Parking lot alone accounts for more than 11% of these impervious surfaces. Contrast to impervious parking lot, turfgrass can accouter for 12% of urban land in California. Irrigated urban landscapes create considerable benefits to our daily living. However, the use of fertilizers and pesticides has caused environmental problems. Preventing fertilizers and pesticides from entering storm drains is an important goal for both landscape and storm runoff managers. Studies of urban runoff have found that the most fertilizers and pesticides are from dry weather runoff which conveys pollutants to sidewalks, streets, and storm drains. Controlling surface runoff is critical to preventing these pollutants from entering storm drains and water bodies. Large scale construction of runoff retention basins and treatment facilities to meet TMDL (Total Maximum Daily Load) regulations are not cost-effective or practical. An alternative approach is to control runoff and nutrients on-site through installation of decentralized BMPs that detain and infiltrate runoff before it reaches storm drains. Recent developed green-infrastructure which integrating engineered soil and trees to reduce runoff and nutrients loading is a self-sustained best management practice (BMP). This BMP has been testing and used in urban runoff control. In Davis, CA this type of BMPs were installed in a parking lot and a residential property to evaluate the system’s effectiveness on reducing storm runoff and pollutant loading from the parking lot and irrigated landscape. Storm runoff and pollutant loading were measured and monitored during February 2007 thru May 2009 from the parking lot. The BMP reduced surface runoff and nutrients by 88.8% and 95.3%, respectively. In the residential irrigated landscape, the dry-weather runoff was monitored during 2007 irrigation season, the BMP captured almost all dry weather runoff. The performance of these BMPs demonstrated their potential use for reducing runoff and nutrients loading. Control urban runoff from these 23% landscape (i.e., parking lot and irrigated turf grass) could largely alter the runoff and nutrients transport and their dynamic in our water system.

  5. Static Mechanical Loading Influences the Expression of Extracellular Matrix and Cell Adhesion Proteins in Vaginal Cells Derived From Premenopausal Women With Severe Pelvic Organ Prolapse.

    PubMed

    Kufaishi, Hala; Alarab, May; Drutz, Harold; Lye, Stephen; Shynlova, Oksana

    2016-08-01

    Primary human vaginal cells derived from women with severe pelvic organ prolapse (POP-HVCs) demonstrate altered cellular characteristics as compared to cells derived from asymptomatic women (control-HVCs). Using computer-controllable Flexcell stretch unit, we examined whether POP-HVCs react differently to mechanical loading as compared to control-HVCs by the expression of extracellular matrix (ECM) components, cell-ECM adhesion proteins, and ECM degrading and maturating enzymes. Vaginal tissue biopsies from premenopausal patients with Pelvic Organ Prolapse Quantification System stage ≥3 (n = 8) and asymptomatic controls (n = 7) were collected during vaginal hysterectomy or repair. Human vaginal cells were isolated by enzymatic digestion, seeded on collagen (COLI)-coated plates, and stretched (24 hours, 25% elongation). Total RNA was extracted, and 84 genes were screened using Human ECM and Adhesion Molecules polymerase chain reaction array; selected genes were verified by quantitative reverse transcription-polymerase chain reaction. Stretch-conditioned media (SCM) were collected and analyzed by protein array, immunoblotting, and zymography. In mechanically stretched control-HVCs, transcript levels of integrins (ITGA1, ITGA4, ITGAV, and ITGB1) and matrix metalloproteinases (MMPs) 2, 8, and 13 were downregulated (P < .05); in POP-HVCs, MMP1, MMP3, and MMP10, ADAMTS8 and 13, tissue inhibitor of metalloproteinases (TIMPs) 1 to 3, ITGA2, ITGA4, ITGA6, ITGB1, contactin (CNTN1), catenins (A1 and B1), and laminins (A3 and C1) were significantly upregulated, whereas COLs (1, 4, 5, 6, 11, and 12) and LOXL1 were downregulated. Human vaginal cells massively secrete MMPs and TIMPs proteins; MMP1, MMP8, MMP9 protein expression and MMP2 gelatinase activity were increased, whereas TIMP2 decreased in SCM from POP-HVCs compared to control-HVCs. Primary human vaginal cells derived from women with severe pelvic organ prolapse and control-HVCs react differentially to in vitro mechanical stretch. Risk factors that induce stretch may alter ECM composition and cell-ECM interaction in pelvic floor tissue leading to the abatement of pelvic organ support and subsequent POP development. © The Author(s) 2016.

  6. The Location-Specific Role of Proteoglycans in the Flexor Carpi Ulnaris Tendon

    PubMed Central

    Buckley, Mark R.; Huffman, George R.; Iozzo, Renato V.; Birk, David E.; Soslowsky, Louis J.

    2015-01-01

    Tendons like the flexor carpi ulnaris (FCU) that contain region-specific distributions of proteoglycans (PGs) as a result of the heterogeneous, multi-axial loads they are subjected to in vivo provide valuable models for understanding structure-function relationships in connective tissues. However, the contributions of specific PGs to FCU tendon mechanical properties are unknown. Therefore, the objective of this study was to determine how the location-dependent, viscoelastic mechanical properties of the FCU tendon are impacted individually by PG-associated glycosaminoglycans (GAGs) and by two small leucine-rich proteoglycans (SLRPs), biglycan and decorin. Full length FCU tendons from biglycan- and decorin-null mice were compared to wild type mice to evaluate the effects of specific SLRPs, while chondroitinase ABC digestion of isolated specimens removed from the tendon midsubstance was used to determine how chontroitin/dermatan sulfate (CS/DS) GAGs impact mechanics in mature FCU tendons. A novel combined genetic knockout/ digestion technique also was employed to compare SLRP-null and wild-type tendons in the absence of CS/DS GAGs that may impact properties in the mature state. In all genotypes, mechanical properties in the FCU tendon midsubstance were not affected by GAG digestion. Full-length tendons exhibited complex, multi-axial deformation under tension that may be associated with their in vivo loading environment. Mechanical properties were adversely affected by the absence of biglycan, and a decreased modulus localized in the center of the tendon was measured. These results help elucidate the role that local alterations in proteoglycan levels may play in processes that adversely impact tendon functionality including injury and pathology. PMID:23941206

  7. Cisplatin loaded PMMA: mechanical properties, surface analysis and effects on Saos-2 cell culture.

    PubMed

    Özben, Hakan; Eralp, Levent; Baysal, Gökhan; Cort, Ayşegül; Sarkalkan, Nazli; Özben, Tomris

    2013-01-01

    Despite wide resection and systemic chemotherapy, bone tumors may present with local recurrences, metastases and pathological fractures. Application of bone cement containing antineoplastic drug to fill the defect after resection of metastatic lesions and to support implants has been suggested to prevent local tumor growth and implant failures. In this study, we aimed to demonstrate the effects of the addition of cisplatin which is a widely used antineoplastic drug for osteosarcoma, on the mechanical properties of bone cement, and to evaluate the cytotoxic effects of eluted cisplatin on Saos-2 cell culture. Two cement samples were prepared by mixing 100 mg and 300 mg of cisplatin powder with 40 g cement powder. The bone cement of the control group did not contain cisplatin. Mechanical analyses included 4-point bending, compression and shear testing. For cytotoxicity analysis, samples were incubated in Dulbecco's Modified Eagle's medium for 15 days. Mediums were applied to Saos-2 cell culture and cell viability was measured. Surface analyses were performed by scanning electron microscope (SEM). The addition of cisplatin did not alter the mechanical properties of bone cement. It was observed that the eluted cisplatin had cytotoxic effects on Saos-2 cells. SEM analyses demonstrated cisplatin granules on the surface of cement samples. Cisplatin maintains its cytotoxic property when released from bone cement without compromising the mechanical stability. Application of cisplatin loaded bone cement may help local control of tumor growth. We believe that our study will shed light on to these new practices for the treatment of bone cancers and will encourage future studies.

  8. The Endoplasmic Reticulum and the Unfolded Protein Response

    PubMed Central

    Malhotra, Jyoti D.; Kaufman, Randal J.

    2009-01-01

    The endoplasmic reticulum (ER) is the site where proteins enter the secretory pathway. Proteins are translocated into the ER lumen in an unfolded state and require protein chaperones and catalysts of protein folding to attain their final appropriate conformation. A sensitive surveillance mechanism exists to prevent misfolded proteins from transiting the secretory pathway and ensures that persistently misfolded proteins are directed towards a degradative pathway. In addition, those processes that prevent accumulation of unfolded proteins in the ER lumen are highly regulated by an intracellular signaling pathway known as the unfolded protein response (UPR). The UPR provides a mechanism by which cells can rapidly adapt to alterations in client protein-folding load in the ER lumen by expanding the capacity for protein folding. In addition, a variety of insults that disrupt protein folding in the ER lumen also activate the UPR. These include changes in intralumenal calcium, altered glycosylation, nutrient deprivation, pathogen infection, expression of folding-defective proteins, and changes in redox status. Persistent protein misfolding initiates apoptotic cascades that are now known to play fundamental roles in the pathogenesis of multiple human diseases including diabetes, atherosclerosis and neurodegenerative diseases. PMID:18023214

  9. Effect of Impaction Sequence on Osteochondral Graft Damage: The Role of Repeated and Varying Loads

    PubMed Central

    Kang, Richard W.; Friel, Nicole A.; Williams, James M.; Cole, Brian J.; Wimmer, Markus A.

    2013-01-01

    Background Osteochondral autografts and allografts require mechanical force for proper graft placement into the defect site; however, impaction compromises the tissue. This study aimed to determine the effect of impaction force and number of hits to seat the graft on cartilage integrity. Hypothesis Under constant impulse conditions, higher impaction load magnitudes are more detrimental to cell viability, matrix integrity and collagen network organization and will result in proteoglycan loss and nitric oxide release. Study Design Controlled laboratory study Methods Osteochondral explants, harvested from fresh bovine trochleas, were exposed to a series of consistent impact loads delivered by a pneumatically driven device. Each plug received the same overall impulse of 7 Ns, reflecting the mean of 23 clinically inserted plugs. Impaction loads of 37.5N, 75N, 150N, and 300N were matched with 74, 37, 21, and 11 hits respectively. Following impaction, the plugs were harvested and cartilage was analyzed for cell viability, histology by safranin-o and picosirius red, and release of sulfated glycosaminoglycans and nitric oxide. Data were compared with non-impacted control. Results Impacted plugs had significantly lower cell viability than non-impacted plugs. A dose response relationship in loss of cell viability with respect to load magnitude was seen immediately and after 4 days but lost after 8 days. Histologic analysis revealed intact cartilage surface in all samples (loaded or control), with loaded samples showing alterations in birefringence. While the sulfated GAG release was similar across varying impaction loads, release of nitric oxide increased with increasing impaction magnitudes and time. Conclusions Impaction loading parameters have a direct effect on the time course of the viability of the cartilage in the graft tissue. Clinical Relevance Optimal loading parameters for surgical impaction of osteochondral grafts are those with lower load magnitudes and a greater number of hits to ensure proper fit. PMID:19915099

  10. Physiological joint line total knee arthroplasty designs are especially sensitive to rotational placement - A finite element analysis.

    PubMed

    Moewis, Philippe; Checa, Sara; Kutzner, Ines; Hommel, Hagen; Duda, Georg N

    2018-01-01

    Mechanical and kinematical aligning techniques are the usual positioning methods during total knee arthroplasty. However, alteration of the physiological joint line and unbalanced medio-lateral load distribution are considered disadvantages in the mechanical and kinematical techniques, respectively. The aim of this study was to analyse the influence of the joint line on the strain and stress distributions in an implanted knee and their sensitivity to rotational mal-alignment. Finite element calculations were conducted to analyse the stresses in the PE-Inlay and the mechanical strains at the bone side of the tibia component-tibia bone interface during normal positioning of the components and internal and external mal-rotation of the tibial component. Two designs were included, a horizontal and a physiological implant. The loading conditions are based on internal knee joint loads during walking. A medialization of the stresses on the PE-Inlay was observed in the physiological implant in a normal position, accompanied by higher stresses in the mal-rotated positions. Within the tibia component-tibia bone interface, similar strain distributions were observed in both implant geometries in the normal position. However, a medialization of the strains was observed in the physiological implant in both mal-rotated conditions with greater bone volume affected by higher strains. Although evident changes due to mal-rotation were observed, the stresses do not suggest a local plastic deformation of the PE-Inlay. The strains values within most of the tibia component-tibia bone interface were in the physiological strain zone and no significant bone changes would be expected. The physiological cut on the articular aspect showed no detrimental effect compared to the horizontal implant.

  11. Use of the Frank-Starling mechanism during exercise is linked to exercise-induced changes in arterial load

    PubMed Central

    Chantler, Paul D.; Melenovsky, Vojtech; Schulman, Steven P.; Gerstenblith, Gary; Becker, Lewis C.; Ferrucci, Luigi; Fleg, Jerome L.; Najjar, Samer S.

    2012-01-01

    Effective arterial elastance(EA) is a measure of the net arterial load imposed on the heart that integrates the effects of heart rate(HR), peripheral vascular resistance(PVR), and total arterial compliance(TAC) and is a modulator of cardiac performance. To what extent the change in EA during exercise impacts on cardiac performance and aerobic capacity is unknown. We examined EA and its relationship with cardiovascular performance in 352 healthy subjects. Subjects underwent rest and exercise gated scans to measure cardiac volumes and to derive EA[end-systolic pressure/stroke volume index(SV)], PVR[MAP/(SV*HR)], and TAC(SV/pulse pressure). EA varied with exercise intensity: the ΔEA between rest and peak exercise along with its determinants, differed among individuals and ranged from −44% to +149%, and was independent of age and sex. Individuals were separated into 3 groups based on their ΔEAI. Individuals with the largest increase in ΔEA(group 3;ΔEA≥0.98 mmHg.m2/ml) had the smallest reduction in PVR, the greatest reduction in TAC and a similar increase in HR vs. group 1(ΔEA<0.22 mmHg.m2/ml). Furthermore, group 3 had a reduction in end-diastolic volume, and a blunted increase in SV(80%), and cardiac output(27%), during exercise vs. group 1. Despite limitations in the Frank-Starling mechanism and cardiac function, peak aerobic capacity did not differ by group because arterial-venous oxygen difference was greater in group 3 vs. 1. Thus the change in arterial load during exercise has important effects on the Frank-Starling mechanism and cardiac performance but not on exercise capacity. These findings provide interesting insights into the dynamic cardiovascular alterations during exercise. PMID:22003052

  12. The effect of mechanical loads on the degradation of aliphatic biodegradable polyesters.

    PubMed

    Li, Ying; Chu, Zhaowei; Li, Xiaoming; Ding, Xili; Guo, Meng; Zhao, Haoran; Yao, Jie; Wang, Lizhen; Cai, Qiang; Fan, Yubo

    2017-06-01

    Aliphatic biodegradable polyesters have been the most widely used synthetic polymers for developing biodegradable devices as alternatives for the currently used permanent medical devices. The performances during biodegradation process play crucial roles for final realization of their functions. Because physiological and biochemical environment in vivo significantly affects biodegradation process, large numbers of studies on effects of mechanical loads on the degradation of aliphatic biodegradable polyesters have been launched during last decades. In this review article, we discussed the mechanism of biodegradation and several different mechanical loads that have been reported to affect the biodegradation process. Other physiological and biochemical factors related to mechanical loads were also discussed. The mechanical load could change the conformational strain energy and morphology to weaken the stability of the polymer. Besides, the load and pattern could accelerate the loss of intrinsic mechanical properties of polymers. This indicated that investigations into effects of mechanical loads on the degradation should be indispensable. More combination condition of mechanical loads and multiple factors should be considered in order to keep the degradation rate controllable and evaluate the degradation process in vivo accurately. Only then can the degradable devise achieve the desired effects and further expand the special applications of aliphatic biodegradable polyesters.

  13. Prediction of glycosaminoglycan synthesis in intervertebral disc under mechanical loading.

    PubMed

    Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

    2016-09-06

    The loss of glycosaminoglycan (GAG) content is a major biochemical change during intervertebral disc (IVD) degeneration. Abnormal mechanical loading is one of the major factors causing disc degeneration. In this study, a multiscale mathematical model was developed to quantify the effect of mechanical loading on GAG synthesis. This model was based on a recently developed cell volume dependent GAG synthesis theory that predicts the variation of GAG synthesis rate of a cell under the influence of mechanical stimuli, and the biphasic theory that describes the deformation of IVD under mechanical loading. The GAG synthesis (at the cell level) was coupled with the mechanical loading (at the tissue level) via a cell-matrix unit approach which established a relationship between the variation of cell dilatation and the local tissue dilatation. This multiscale mathematical model was used to predict the effect of static load (creep load) on GAG synthesis in bovine tail discs. The predicted results are in the range of experimental results. This model was also used to investigate the effect of static (0.2MPa) and diurnal loads (0.1/0.3MPa and 0.15/0.25MPa in 12/12 hours shift with an average of 0.2MPa over a cycle) on GAG synthesis. It was found that static load and diurnal loads have different effects on GAG synthesis in a diurnal cycle, and the diurnal load effects depend on the amplitude of the load. The model is important to understand the effect of mechanical loading at the tissue level on GAG synthesis at the cellular level, as well as to optimize the mechanical loading in growing engineered tissue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Manipulating electronic and mechanical properties at metal-ceramic interfaces with a nanomolecular layer

    NASA Astrophysics Data System (ADS)

    Kwan, Matthew P.

    This work demonstrates that inserting nanomolecular layers (NMLs) can profoundly change and/or lead to novel electronic and mechanical properties of metal-ceramic interfaces. The first set of results demonstrate that organophosphonate NMLs up to 1.8 nm thick can alter metal work functions by +/- 0.6 eV. This work function change is a strong function of the NML terminal groups (methyl, mercaptan, carboxylic acid, or phosphonic acid), morphology (up right, lying down, or mixed orientation), and the nature of the bonding (covalent, polar, or Van der Waals) between NML and the adjacent layers. Additionally, while NML-ceramic bond type and strength can influence and counteract the effect of NML morphology, the metal-NML bond appears to be independent of the morphology of the NML underlayer. The second set of results demonstrate that inserting an organosilane NML at a metal-ceramic interface can lead to multifold fracture toughening under both static (stress corrosion) and cyclic loads (fatigue) tested in four-point bend. Nanolayer-induced interface strengthening during static loading activates metal plasticity above the metal yield strength, leading to two-fold fracture toughening. Metal plasticity-induced toughening increases as temperature is increased up to 85 °C due to decreasing yield stress. In the fatigue fracture tests I report for the first time a loading-frequency-dependent tripling in fracture toughening in the 75-300 Hz range upon inserting a mercapto-silane NML at the weakest interface of a ceramic-polymer-metal-ceramic stack. This unusual behavior arises from the NML strengthened interface enabling load transfer to- and plasticity in the polymer layer, while the fatigue toughening magnitude and frequency range are determined by polymer rheology.

  15. The Effects of a Lower Body Exoskeleton Load Carriage Assistive Device on Oxygen Consumption and Kinematics During Walking with Loads

    DTIC Science & Technology

    2006-11-01

    analyze the associated gait biomechanics . Ten Army enlisted men participated in the study. Oxygen consumption (VO2) and gait biomechanics were...measured while Soldiers walked at 4.83 km/h and 0% grade under three realistic load weight configurations that were comprised of Army clothing and...increases users’ metabolic cost while carrying various loads and alters their gait biomechanics compared to conventional load carriage using a backpack

  16. Denatured protein-coated docetaxel nanoparticles: Alterable drug state and cytosolic delivery.

    PubMed

    Zhang, Li; Xiao, Qingqing; Wang, Yiran; Zhang, Chenshuang; He, Wei; Yin, Lifang

    2017-05-15

    Many lead compounds have a low solubility in water, which substantially hinders their clinical application. Nanosuspensions have been considered a promising strategy for the delivery of water-insoluble drugs. Here, denatured soy protein isolate (SPI)-coated docetaxel nanosuspensions (DTX-NS) were developed using an anti-solvent precipitation-ultrasonication method to improve the water-solubility of DTX, thus improving its intracellular delivery. DTX-NS, with a diameter of 150-250nm and drug-loading up to 18.18%, were successfully prepared by coating drug particles with SPI. Interestingly, the drug state of DTX-NS was alterable. Amorphous drug nanoparticles were obtained at low drug-loading, whereas at a high drug-loading, the DTX-NS drug was mainly present in the crystalline state. Moreover, DTX-NS could be internalized at high levels by cancer cells and enter the cytosol by lysosomal escape, enhancing cell cytotoxicity and apoptosis compared with free DTX. Taken together, denatured SPI has a strong stabilization effect on nanosuspensions, and the drug state in SPI-coated nanosuspensions is alterable by changing the drug-loading. Moreover, DTX-NS could achieve cytosolic delivery, generating enhanced cell cytotoxicity against cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Proteomic and phosphoproteomic analysis of renal cortex in a salt-load rat model of advanced kidney damage

    PubMed Central

    Jiang, Shaoling; He, Hanchang; Tan, Lishan; Wang, Liangliang; Su, Zhengxiu; Liu, Yufeng; Zhu, Hongguo; Zhang, Menghuan; Hou, Fan Fan; Li, Aiqing

    2016-01-01

    Salt plays an essential role in the progression of chronic kidney disease and hypertension. However, the mechanisms underlying pathogenesis of salt-induced kidney damage remain largely unknown. Here, Sprague-Dawley rats, that underwent 5/6 nephrectomy (5/6Nx, a model of advanced kidney damage) or sham operation, were treated for 2 weeks with a normal or high-salt diet. We employed aTiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for proteomic and phosphoproteomic profiling of the renal cortex. We found 318 proteins differentially expressed in 5/6Nx group relative to sham group, and 310 proteins significantly changed in response to salt load in 5/6Nx animals. Totally, 1810 unique phosphopeptides corresponding to 550 phosphoproteins were identified. We identified 113 upregulated and 84 downregulated phosphopeptides in 5/6Nx animals relative to sham animals. Salt load induced 78 upregulated and 91 downregulated phosphopeptides in 5/6Nx rats. The differentially expressed phospholproteins are important transporters, structural molecules, and receptors. Protein-protein interaction analysis revealed that the differentially phosphorylated proteins in 5/6Nx group, Polr2a, Srrm1, Gsta2 and Pxn were the most linked. Salt-induced differential phosphoproteins, Myh6, Lmna and Des were the most linked. Altered phosphorylation levels of lamin A and phospholamban were validated. This study will provide new insight into pathogenetic mechanisms of chronic kidney disease and salt sensitivity. PMID:27775022

  18. Acetabular cartilage defects cause altered hip and knee joint coordination variability during gait.

    PubMed

    Samaan, Michael A; Teng, Hsiang-Ling; Kumar, Deepak; Lee, Sonia; Link, Thomas M; Majumdar, Sharmila; Souza, Richard B

    2015-12-01

    Patients with acetabular cartilage defects reported increased pain and disability compared to those without acetabular cartilage defects. The specific effects of acetabular cartilage defects on lower extremity coordination patterns are unclear. The purpose of this study was to determine hip and knee joint coordination variability during gait in those with and without acetabular cartilage defects. A combined approach, consisting of a semi-quantitative MRI-based quantification method and vector coding, was used to assess hip and knee joint coordination variability during gait in those with and without acetabular cartilage lesions. The coordination variability of the hip flexion-extension/knee rotation, hip abduction-adduction/knee rotation, and hip rotation/knee rotation joint couplings were reduced in the acetabular lesion group compared to the control group during loading response of the gait cycle. The lesion group demonstrated increased variability in the hip flexion-extension/knee rotation and hip abduction-adduction/knee rotation joint couplings, compared to the control group, during the terminal stance/pre-swing phase of gait. Reduced variability during loading response in the lesion group may suggest reduced movement strategies and a possible compensation mechanism for lower extremity instability during this phase of the gait cycle. During terminal stance/pre-swing, a larger variability in the lesion group may suggest increased movement strategies and represent a compensation or pain avoidance mechanism caused by the load applied to the hip joint. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Countermovement Jump Performance with Increased Training Loads in Elite Female Rugby Athletes.

    PubMed

    Gathercole, R; Sporer, B; Stellingwerff, T

    2015-08-01

    Countermovement jump (CMJ) performance is typically analyzed through single-point concentric-based variables (e. g., peak power or force and height). However, methodological approaches examining movement strategies may be more sensitive to neuromuscular fatigue. 12 elite female rugby sevens athletes undertook weekly CMJ testing throughout a 6-week training block involving progressively increased training loads. Athletes self-reported training load (TRIMP) and wellness daily. 22 CMJ variables were assessed, incorporating analyses of force, velocity, power and time measured during eccentric and concentric jump phases. Differences over time were examined using the magnitude of change (effect sizes; ES) compared to baseline. Pearson correlations examined relationships between CMJ variables, wellness and TRIMP. TRIMP displayed large increases (mean ES; weeks 2-6: 2.47). Wellness decreased in week 3 (-0.41), with small reductions following (weeks 4-6: -0.34). Flight time (weeks 3-6: -1.84), peak displacement (weeks 2-6: -2.24), time to peak force (weeks 3-6: 2.58), force at zero velocity (F@0V) (weeks 5-6: -1.28) displayed multiple changes indicative of diminished neuromuscular function. Wellness scores and max rate of force development (mean; r=0.32), F@0V (r=0.28) and flight time (r=0.34) displayed positive correlations. Intensified training decreased CMJ output and altered CMJ mechanics. Longitudinal neuromuscular fatigue monitoring of team-sport athletes appears improved through CMJ mechanics analysis. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Perlecan-containing pericellular matrix regulates solute transport and mechanosensing within the osteocyte lacunar-canalicular system

    PubMed Central

    Wang, Bin; Lai, Xiaohan; Price, Christopher; Thompson, William R.; Li, Wen; Quabili, Tonima R.; Tseng, Wei-Ju; Liu, Xiaowei Sherry; Zhang, Hong; Pan, Jun; Kirn-Safran, Catherine B.; Farach-Carson, Mary C.; Wang, Liyun

    2013-01-01

    The pericellular matrix (PCM), a thin “coating” surrounding nearly all mammalian cells, plays a critical role in many cell-surface phenomena. In osteocytes, the PCM is believed to control both “outside-in” (mechanosensing) and “inside-out” (signaling molecule transport) processes. However, the osteocytic PCM is challenging to study in situ because it is thin (~100nm) and enclosed in mineralized matrix. To this end, we recently developed a novel tracer velocimetry approach that combined fluorescence recovery after photobleaching (FRAP) imaging with hydrodynamic modeling to quantify the osteocytic PCM in young murine bone (Wang et al., J Bone Miner Res. 2013; 28:1075–86). In this study, we applied the technique to older mice expressing or deficient for perlecan/HSPG2, a large heparan-sulfate proteoglycan normally secreted in osteocytic PCM. The objectives were to i) characterize transport within an altered PCM; ii) to test the sensitivity of our approach in detecting the PCM alterations; and iii) to dissect the roles of the PCM in osteocyte mechanosensing. We found that i) solute transport increases in the perlecan-deficient (hypomorphic: Hypo) mice compared with control mice; ii) PCM fiber density decreases with aging and perlecan deficiency; iii) the osteocytes in the Hypo bones are predicted to experience higher shear stress (+34%), but decreased fluid drag force (−35%) under 3N peak tibial loading, and iv) when subjected to tibial loading in a preliminary in vivo experiment, the Hypo mice did not respond to the anabolic stimuli as CTL mice. These findings support the hypothesis that the PCM fibers act as osteocyte’s sensing antennae, regulating load-induced cellular stimulations and thus bone’s sensitivity and in vivo bone adaptation. If this hypothesis is further confirmed, osteocytic PCM could be new targets to develop osteoporosis treatments by modulating bone’s intrinsic sensitivity to mechanical loading and be used to design patient-specific exercise regimens to promote bone formation. PMID:24115222

  1. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance.

    PubMed

    Bindels, Laure B; Neyrinck, Audrey M; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G; Langella, Philippe; Cani, Patrice D; Thissen, Jean-Paul; Delzenne, Nathalie M

    2018-04-06

    Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium ( Faecalibacterium prausnitzii ) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

  2. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance

    PubMed Central

    Bindels, Laure B.; Neyrinck, Audrey M.; Loumaye, Audrey; Catry, Emilie; Walgrave, Hannah; Cherbuy, Claire; Leclercq, Sophie; Van Hul, Matthias; Plovier, Hubert; Pachikian, Barbara; Bermúdez-Humarán, Luis G.; Langella, Philippe; Cani, Patrice D.; Thissen, Jean-Paul; Delzenne, Nathalie M.

    2018-01-01

    Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium (Faecalibacterium prausnitzii) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharide-binding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis. PMID:29719601

  3. A graphical modeling tool for evaluating nitrogen loading to and nitrate transport in ground water in the mid-Snake region, south-central Idaho

    USGS Publications Warehouse

    Clark, David W.; Skinner, Kenneth D.; Pollock, David W.

    2006-01-01

    A flow and transport model was created with a graphical user interface to simplify the evaluation of nitrogen loading and nitrate transport in the mid-Snake region in south-central Idaho. This model and interface package, the Snake River Nitrate Scenario Simulator, uses the U.S. Geological Survey's MODFLOW 2000 and MOC3D models. The interface, which is enabled for use with geographic information systems (GIS), was created using ESRI's royalty-free MapObjects LT software. The interface lets users view initial nitrogen-loading conditions (representing conditions as of 1998), alter the nitrogen loading within selected zones by specifying a multiplication factor and applying it to the initial condition, run the flow and transport model, and view a graphical representation of the modeling results. The flow and transport model of the Snake River Nitrate Scenario Simulator was created by rediscretizing and recalibrating a clipped portion of an existing regional flow model. The new subregional model was recalibrated with newly available water-level data and spring and ground-water nitrate concentration data for the study area. An updated nitrogen input GIS layer controls the application of nitrogen to the flow and transport model. Users can alter the nitrogen application to the flow and transport model by altering the nitrogen load in predefined spatial zones contained within similar political, hydrologic, and size-constrained boundaries.

  4. Frequency sensitive mechanism in low-intensity ultrasound enhanced bioeffects

    PubMed Central

    Chama, Abdoulkadri; Subramanian, Anuradha; Viljoen, Hendrik J.

    2017-01-01

    This study presents two novel theoretical models to elucidate frequency sensitive nuclear mechanisms in low-intensity ultrasound enhanced bioeffects. In contrast to the typical 1.5 MHz pulsed ultrasound regime, our group previously experimentally confirmed that ultrasound stimulation of anchored chondrocytes at resonant frequency maximized gene expression of load inducible genes which are regulatory markers for cellular response to external stimuli. However, ERK phosphorylation displayed no frequency dependency, suggesting that the biochemical mechanisms involved in enhanced gene expression is downstream of ERK phosphorylation. To elucidate such underlying mechanisms, this study presents a theoretical model of an anchored cell, representing an in vitro chondrocyte, in an ultrasound field. The model results showed that the mechanical energy storage is maximized at the chondrocyte’s resonant frequency and the energy density in the nucleus is almost twice as high as in the cytoplasm. Next, a mechanochemical model was developed to link the mechanical stimulation of ultrasound and the increased mechanical energy density in the nucleus to the downstream targets of the ERK pathway. This study showed for the first time that ultrasound stimulation induces frequency dependent gene expression as a result of altered rates of transcription factors binding to chromatin. PMID:28763448

  5. Enhancement of muscle and locomotor performance by a series compliance: A mechanistic simulation study

    PubMed Central

    2018-01-01

    The objective was to better understand how a series compliance alters contraction kinetics and power output of muscle to enhance the work done on a load. A mathematical model was created in which a gravitational point load was connected via a linear spring to a muscle (based on the contractile properties of the sartorius of leopard frogs, Rana pipiens). The model explored the effects of load mass, tendon compliance, and delay between onset of contraction and release of the load (catch) on lift height and power output as measures of performance. Series compliance resulted in increased lift height over a relatively narrow range of compliances, and the effect was quite modest without an imposed catch mechanism unless the load was unrealistically small. Peak power of the muscle-tendon complex could be augmented up to four times that produced with a muscle alone, however, lift height was not predicted by peak power. Rather, lift height was improved as a result of the compliance synchronizing the time courses of muscle force and shortening velocity, in particular by stabilizing shortening velocity such that muscle power was sustained rather than rising and immediately falling. With a catch mechanism, enhanced performance resulted largely from energy storage in the compliance during the period of catch, rather than increased time for muscle activation before movement commenced. However, series compliance introduced a trade-off between work done before versus after release of the catch. Thus, the ability of tendons to enhance locomotor performance (i.e. increase the work done by muscle) appears dependent not only on their established role in storing energy and increasing power, but also on their ability to modulate the kinetics of muscle contraction such that power is sustained over more of the contraction, and maximizing the balance of work done before versus after release of a catch. PMID:29370246

  6. Finite Element Modeling Techniques for Analysis of VIIP

    NASA Technical Reports Server (NTRS)

    Feola, Andrew J.; Raykin, J.; Gleason, R.; Mulugeta, Lealem; Myers, Jerry G.; Nelson, Emily S.; Samuels, Brian C.; Ethier, C. Ross

    2015-01-01

    Visual Impairment and Intracranial Pressure (VIIP) syndrome is a major health concern for long-duration space missions. Currently, it is thought that a cephalad fluid shift in microgravity causes elevated intracranial pressure (ICP) that is transmitted along the optic nerve sheath (ONS). We hypothesize that this in turn leads to alteration and remodeling of connective tissue in the posterior eye which impacts vision. Finite element (FE) analysis is a powerful tool for examining the effects of mechanical loads in complex geometries. Our goal is to build a FE analysis framework to understand the response of the lamina cribrosa and optic nerve head to elevations in ICP in VIIP.

  7. A mechanical protocol to replicate impact in walking footwear.

    PubMed

    Price, Carina; Cooper, Glen; Graham-Smith, Philip; Jones, Richard

    2014-01-01

    Impact testing is undertaken to quantify the shock absorption characteristics of footwear. The current widely reported mechanical testing method mimics the heel impact in running and therefore applies excessive energy to walking footwear. The purpose of this study was to modify the ASTM protocol F1614 (Procedure A) to better represent walking gait. This was achieved by collecting kinematic and kinetic data while participants walked in four different styles of walking footwear (trainer, oxford shoe, flip-flop and triple-density sandal). The quantified heel-velocity and effective mass at ground-impact were then replicated in a mechanical protocol. The kinematic data identified different impact characteristics in the footwear styles. Significantly faster heel velocity towards the floor was recorded walking in the toe-post sandals (flip-flop and triple-density sandal) compared with other conditions (e.g. flip-flop: 0.36±0.05 ms(-1) versus trainer: 0.18±0.06 ms(-1)). The mechanical protocol was adapted by altering the mass and drop height specific to the data captured for each shoe (e.g. flip-flop: drop height 7 mm, mass 16.2 kg). As expected, the adapted mechanical protocol produced significantly lower peak force and accelerometer values than the ASTM protocol (p<.001). The mean difference between the human and adapted protocol was 12.7±17.5% (p<.001) for peak acceleration and 25.2±17.7% (p=.786) for peak force. This paper demonstrates that altered mechanical test protocols can more closely replicate loading on the lower limb in walking. This therefore suggests that testing of material properties of footbeds not only needs to be gait style specific (e.g. running versus walking), but also footwear style specific. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Designing PolyHEMA Substrates that Mimic the Viscoelastic Response of Soft Tissue

    PubMed Central

    Holt, Brian; Tripathi, Anubhav; Morgan, Jeffrey R.

    2011-01-01

    Matching the mechanical properties of a biomaterial to soft tissue is often overlooked despite the fact that it’s well known that cells respond to and are capable of changing their mechanical environment. In this paper, we used NaCl and alginate beads as porogens to make a series of micro- and macro-porous pHEMA substrates [poly(2-hydroxyethly methacrylate)] and quantified their mechanical behavior under low-magnitude shear loads over physiologically relevant frequencies. Using a stress-controlled rheometer, we performed isothermal (37°C) frequency response experiments between 0.628 and 75.4 rad/s [0.01–12Hz] at 0.1% strain. Both micro- and macro-porous pHEMA substrates were predominately elastic in nature with a narrow range of G′ and G″ values that mimicked the response of human skin. The magnitude of the G′ and G″ values of the macro-porous substrates were designed to closely match human skin. To determine how cell growth might alter their mechanical properties, pHEMA substrates were functionalized and human skin fibroblasts grown on them for fourteen days. As a result of cell growth, the magnitude of G′ and G″ increased at low frequencies while also altering the degree of high frequency dependence, indicating that cellular interactions with the micro-pore infrastructure has a profound effect on the viscoelastic behavior of the substrates. These data could be fit to a mathematical model describing a soft solid. A quantitative understanding of the mechanical behavior of biomaterials in regimes that are physiologically relevant and how these mechanics may change after implantation may aid in the design of new materials. PMID:21496821

  9. Non-Invasive Tension Measurement Devices for Parachute Cordage

    NASA Technical Reports Server (NTRS)

    Litteken, Douglas A.; Daum, Jared S.

    2016-01-01

    The need for lightweight and non-intrusive tension measurements has arisen alongside the development of high-fidelity computer models of textile and fluid dynamics. In order to validate these computer models, data must be gathered in the operational environment without altering the design, construction, or performance of the test article. Current measurement device designs rely on severing a cord and breaking the load path to introduce a load cell. These load cells are very reliable, but introduce an area of high stiffness in the load path, directly affecting the structural response, adding excessive weight, and possibly altering the dynamics of the parachute during a test. To capture the required data for analysis validation without affecting the response of the system, non-invasive measurement devices have been developed and tested by NASA. These tension measurement devices offer minimal impact to the mass, form, fit, and function of the test article, while providing reliable, axial tension measurements for parachute cordage.

  10. The mechanism of phloem loading in rice (Oryza sativa).

    PubMed

    Eom, Joon-Seob; Choi, Sang-Bong; Ward, John M; Jeon, Jong-Seong

    2012-05-01

    Carbohydrates, mainly sucrose, that are synthesized in source organs are transported to sink organs to support growth and development. Phloem loading of sucrose is a crucial step that drives long-distance transport by elevating hydrostatic pressure in the phloem. Three phloem loading strategies have been identified, two active mechanisms, apoplastic loading via sucrose transporters and symplastic polymer trapping, and one passive mechanism. The first two active loading mechanisms require metabolic energy, carbohydrate is loaded into the phloem against a concentration gradient. The passive process, diffusion, involves equilibration of sucrose and other metabolites between cells through plasmodesmata. Many higher plant species including Arabidopsis utilize the active loading mechanisms to increase carbohydrate in the phloem to higher concentrations than that in mesophyll cells. In contrast, recent data revealed that a large number of plants, especially woody species, load sucrose passively by maintaining a high concentration in mesophyll cells. However, it still remains to be determined how the worldwide important cereal crop, rice, loads sucrose into the phloem in source organs. Based on the literature and our results, we propose a potential strategy of phloem loading in rice. Elucidation of the phloem loading mechanism should improve our understanding of rice development and facilitate its manipulation towards the increase of crop productivity.

  11. Mechanism isolates load weighing cell during lifting of load

    NASA Technical Reports Server (NTRS)

    Haigler, J. S.

    1966-01-01

    Load weighing cell used in conjuction with a hoist is isolated during lifting and manipulation of the load. A simple mechanism, attached to a crane hook, provides a screw adjustment for engaging the load cell during weighing of the load and isolating it from lift forces during hoisting of the load.

  12. Osteoarthritis of the ankle and foot complex in former Greek soccer players.

    PubMed

    Armenis, Elias; Pefanis, Nikolaos; Tsiganos, Georgios; Karagounis, Panagiotis; Baltopoulos, Panagiotis

    2011-12-01

    Sports activities cause increased loads in elite athletes' joints. Current scientific knowledge highlights the importance of applied mechanical loads on the physiology and pathophysiology of the articular cartilage. Thus, it is possible that sporting activity has a role in the development of osteoarthritis (OA), a painful and damaging joint disease. The aim of the present study was to investigate and record osteoarthritic alterations in the ankle and foot complex in former Greek soccer players and also compare them with those in the general population. The study sample consisted of 170 male, former elite soccer players, aged between 42 and 55 years (mean = 49.8 years, standard deviation [SD] = 7.4). A control group of 132 men, aged between 42 and 55 years (mean, 50.7 years, SD = 9.9), with no regular athletic activity were examined. The development of osteoarthritic alterations was recorded through a questionnaire and clinical and radiological examination. Radiographic analysis of the images in former athletes group showed not only more signs of cartilage degeneration in comparison with the control group (P < .05) but also similar clinical manifestations (pain and impaired mobility; P > .05). Osteophyte formation is a frequent disease among former soccer players--with variations on radiographic images--but it does not appear in their clinical picture. However, it is likely that both spurs and subchondral sclerosis (main findings) are preclinical manifestations of OA. Prognostic, Level II.

  13. Effect of dietary cadmium on iron metabolism in growing rats.

    PubMed

    Crowe, A; Morgan, E H

    1997-07-01

    Little is known regarding the interactions between iron and cadmium during postnatal development. This study examined the effect of altered levels of dietary iron and cadmium loading on the distribution of cadmium and iron in developing rats ages 15, 21, and 63 days. The uptake of iron, transferrin, and cadmium into various organs was also examined using 59Fe, [125I]transferrin, and 109Cd. Dietary cadmium loading reduced packed cell volume and plasma iron and nonheme iron levels in the liver and kidneys, evidence of the inducement of an iron deficient state. Dietary iron loading was able to reverse these effects, suggesting that they were the result of impaired intestinal absorption of iron. Cadmium loading resulted in cadmium concentrations in the liver and kidneys up to 20 microg/g in rats age 63 days, while cadmium levels in the brain reached only 0.16 microg/g, indicating that the blood-brain barrier restricts the entry of cadmium into the brain. Iron loading had little effect on cadmium levels in the organs and cadmium feeding did not lower tissue iron levels in iron loaded animals. These results suggest that cadmium inhibits iron absorption only at low to normal levels of dietary iron and that at high levels of intake iron and cadmium are largely absorbed by other, noncompetitive mechanisms. It was shown that 109Cd is removed from the plasma extremely quickly irrespective of iron status and deposits mainly in the liver. One of the most striking effects of cadmium loading on iron metabolism was increased uptake of [125I]transferrin by the heart, possibly by disrupting the process of receptor-mediated endocytosis and recycling of transferrin by heart muscle.

  14. Female Pelvic Floor Biomechanics: Bridging the Gap

    PubMed Central

    Easley, Deanna C.; Abramowitch, Steven D.; Moalli, Pamela A.

    2017-01-01

    Purpose of review The pelvic floor is a complex assembly of connective tissues and striated muscle that simultaneously counteract gravitational forces, inertial forces, and intraabdominal pressures while maintaining the position of the pelvic organs. In 30% of women, injury or failure of the pelvic floor results in pelvic organ prolapse (POP). Surgical treatments have high recurrence rates, due, in part, to a limited understanding of physiologic loading conditions. It is critical to apply biomechanics to help elucidate how altered loading conditions of the pelvis contribute to the development of pelvic organ prolapse and to define surgeries to restore normal support. Recent findings Evidence suggests the ewe is a potential animal model for studying vaginal properties and that uterosacral and cardinal ligaments experience significant creep, which may be affecting surgical outcomes. A new method of measuring ligament displacements in vivo was developed, and finite element models that simulate urethral support, pelvic floor dynamics, and the impact of episiotomies on the pelvic floor were studied. Summary This review highlights some contributions over the past year, including mechanical testing and the creation of models, which are used to understand pelvic floor changes with loading, and the impact of surgical procedures, to illustrate how biomechanics is being utilized. PMID:28267057

  15. Soot loading in a generic gas turbine combustor

    NASA Technical Reports Server (NTRS)

    Eckerle, W. A.; Rosfjord, T. J.

    1987-01-01

    Variation in soot loading along the centerline of a generic gas turbine combustor was experimentally investigated. The 12.7-cm dia burner consisted of six sheet-metal louvers. Soot loading along the burner length was quantified by acquiring measurements first at the exit of the full-length combustor and then at upstream stations by sequential removal of liner louvers to shorten the burner length. Alteration of the flow field approaching removed louvers, maintaining a constant liner pressure drop. Burner exhaust flow was sampled at the burner centerline to determine soot mass concentration and smoke number. Characteristic particle size and number density, transmissivity of the exhaust flow, and local radiation from luminous soot particles in the exhaust flow were determined by optical techniques. Four test fuels were burned at three fuel-air ratios to determine fuel chemical property and flow temperature influences. Data were acquired at two combustor pressures. Particulate concentration data indicated a strong oxidation mechanism in the combustor secondary zone, though the oxidation was significantly affected by flow temperature. Soot production was directly related to fuel smoke point. Less soot production and lower secondary-zone oxidation rates were observed at reduced combustor pressure.

  16. Prestressing Shock Resistant Mechanical Components and Mechanisms Made from Hard, Superelastic Materials

    NASA Technical Reports Server (NTRS)

    DellaCorte, Christopher (Inventor)

    2014-01-01

    A method and an apparatus confer full superelastic properties to the active surface of a mechanical component constructed of a superelastic material prior to service. A compressive load is applied to the active surface of the mechanical component followed by removing the compressive load from the active surface whereby substantially all load strain is recoverable after applying and removing of subsequent compressive loads.

  17. Influence of screw length and diameter on tibial strain energy density distribution after anterior cruciate ligament reconstruction

    NASA Astrophysics Data System (ADS)

    Yao, Jie; Kuang, Guan-Ming; Wong, Duo Wai-Chi; Niu, Wen-Xin; Zhang, Ming; Fan, Yu-Bo

    2014-04-01

    Postoperative tunnel enlargement has been frequently reported after anterior cruciate ligament (ACL) reconstruction. Interference screw, as a surgical implant in ACL reconstruction, may influence natural loading transmission and contribute to tunnel enlargement. The aims of this study are (1) to quantify the alteration of strain energy den sity (SED) distribution after the anatomic single-bundle ACL reconstruction; and (2) to characterize the influence of screw length and diameter on the degree of the SED alteration. A validated finite element model of human knee joint was used. The screw length ranging from 20 to 30mm with screw diameter ranging from 7 to 9 mm were investigated. In the post-operative knee, the SED increased steeply at the extra-articular tunnel aperture under compressive and complex loadings, whereas the SED decreased beneath the screw shaft and nearby the intra-articular tunnel aperture. Increasing the screw length could lower the SED deprivation in the proximal part of the bone tunnel; whereas increasing either screw length or diameter could aggravate the SED deprivation in the distal part of the bone tunnel. Decreasing the elastic modulus of the screw could lower the bone SED deprivation around the screw. In consideration of both graft stability and SED alteration, a biodegradable interference screw with a long length is recommended, which could provide a beneficial mechanical environment at the distal part of the tunnel, and meanwhile decrease the bone-graft motion and synovial fluid propagation at the proximal part of the tunnel. These findings together with the clinical and histological factors could help to improve surgical outcome, and serve as a preliminary knowledge for the following study of biodegradable interference screw. [Figure not available: see fulltext.

  18. Altered control strategy between leading and trailing leg increases knee adduction moment in the elderly while descending stairs.

    PubMed

    Karamanidis, Kiros; Arampatzis, Adamantios

    2011-02-24

    The aim of the study was to examine the external knee adduction moments in a group of older and younger adults while descending stairs and thus the possibility of an increased risk of knee osteoarthritis due to altered knee joint loading in the elderly. Twenty-seven older and 16 younger adults descended a purpose-built staircase. A motion capture system and a force plate were used to determine the subjects' 3D kinematics and ground reaction forces (GRF) during locomotion. Calculation of the leg kinematics and kinetics was done by means of a rigid, three-segment, 3D leg model. In the initial portion of the support phase, older adults showed a more medio-posterior GRF vector relative to the ankle joint, leading to lower ankle joint moments (P<0.05). At the knee, the older adults demonstrated a more medio-posterior directed GRF vector, increasing in knee flexion and adduction in the second part of the single support phase (P<0.05). Further, GRF magnitude was lower in the initial and higher in the mid-portions of the support phase for the elderly (P<0.05). The results show that older adults descend stairs by using the trailing leg before the initiation of the double support phase more compared to the younger ones. The consequence of this altered control strategy while stepping down is a more medially directed GRF vector increasing the magnitude of external knee adduction moment in the elderly. The observed changes between leading and trailing leg in the elderly may cause a redistribution of the mechanical load at the tibiofemoral joint, affecting the initiation and progression of knee osteoarthritis in the elderly. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. Biomechanical consequences of plantar fascial release or rupture during gait. Part II: alterations in forefoot loading.

    PubMed

    Sharkey, N A; Donahue, S W; Ferris, L

    1999-02-01

    With a model using feet from cadavers, we tested the hypothesis that plantar fascial release or rupture alters the loading environment of the forefoot during the latter half of the stance phase of gait. The model simulated the position and loading environment of the foot at two instants: early in terminal stance immediately after heel-off and late in terminal stance just preceding contralateral heel strike. Eight feet were loaded at both positions by simulated plantar flexor contraction, and the distribution of plantar pressure was measured before and after progressive release of the plantar fascia. Strain in the diaphysis of the second metatarsal was also measured, from which the bending moments and axial force imposed on the metatarsal were calculated. Cutting the medial half of the central plantar fascial band significantly increased peak pressure under the metatarsal heads but had little effect on pressures in other regions of the forefoot or on second metatarsal strain and loading. Dividing the entire central band or completely releasing the plantar fascia from the calcaneus had a much greater effect and caused significant shifts in plantar pressure and force from the toes to beneath the metatarsal heads. These shifts were accompanied by significantly increased strain and bending in the second metatarsal. Complete fasciotomy increased the magnitude of strain in the dorsal aspect of the second metatarsal by more than 80%, suggesting that plantar fascial release or rupture accelerates the accumulation of fatigue damage in these bones. Altered forefoot loading may be a potential complication of plantar fasciotomy.

  20. Genomic variation in the MMP-1 promoter influences estrogen receptor mediated activity in a mechanically activated environment: potential implications for microgravity risk assessment

    NASA Astrophysics Data System (ADS)

    Thaler, John; Myers, Ken; Lu, Ting; Hart, David

    Background: Mechanotransduction, the conversion of mechanical forces (tensile, compression, shear etc.) into cellular signals is a significant response mechanism in bone that contributes to the balance between formation and resorption and helps maintain bone density. In microgravity the lack of mechanical signals can lead to a loss of bone density, however the signaling pathways responsible are not well understood. For women, sex-specific hormones are also important in maintaining bone density since estrogen deficiency is a major factor in the etiology of osteoporosis in postmenopausal women. Estrogen Receptors (ERs) are present in human connective tissue cells such as osteoblasts and may play a role in mechanotransduction responses. The two ER isoforms, alpha (ER-α) and beta (ER-β) differentially regulate expression of matrixmetalloproteinases (MMPs) which degrade extracellular matrix components found in connective tissues. Mechanical stimulation is known to affect the expression of MMP-1, a collagenase involved in the bone resorption process. The MMP-1 promoter region contains a single nucleotide polymorphism of an additional guanine (G) at position -1607 bp which creates a binding site for a member of the Ets family of mammalian transcription factors. The 2G allele is known to be present in 45-70% of healthy populations and has been associated with higher MMP-1 expression. The 2G allele has been linked to higher risk of several types of cancer but a link to osteoporosis or microgravity induced bone loss has not been explored. The purpose of the present study was to conduct a case-study to determine whether small genetic variations can influence cellular and tissue responses to mechanical loading. Specifically we examined the potential of the 1G/2G -1607 MMP-1 promoter SNP to alter the interplay between mechanical shear stress and estrogen receptors in controlling MMP-1 expression. Methods: Rabbit synovial cells (HIG-82) were used as an in vitro model system to examine the potential impact of the 1G/2G SNP on the cellular response to mechanical loading. HIG-82 cells are estrogen receptor (ER) negative and were transiently transfected with SV40 expression vectors for either ER-α or ER-β isoforms. Cells grown on glass slides were also co-transfected with either a 1G or 2G MMP-1 promoter-luciferase construct. Transfected cells were subjected to dynamic shear stress in a Flexcell Streamer Shear Stress Device. The dynamic loading regime was 0.5 Hz, 10 dyn/cm2 shear for 1 minute followed by 14 minutes rest and repeated for 8 hrs. A Promega Dual Luciferase Reporter Assay System was used to assess MMP-1 promoter activity. Results: Shear stress loading increased both 1G and 2G MMP-1 promoter activity compared to unloaded controls, however the 2G promoter had significantly higher rates of expression than the 1G promoter across all loading regimes and ER co-transfections. Transfection with ER-β resulted in higher MMP-1 promoter activity than that in cells expressing ER-α or in ER-neg cells. Conclusions: Specific genomic variations can lead to differences in cellular responses to changes in mechanical loading environments such as are encountered in microgravity environments or earth-based analogs. These genomic differences may predispose individuals to greater risk of bone loss. It is important to understand the combined effects of mechanical loading, genetic variation and sex hormones on bone maintenance so that risks can be identified for microgravity or analog environments, and specific interventions developed to counteract such risk or even exclude some individuals from prolonged space environments due to the extent of the risk.

  1. Nitrogen balance for a plantation forest drainage canal on the North Carolina Coastal Plain

    Treesearch

    Timothy W. Appelboom; George M. Chescheir; R. Wayne Skaggs; J. Wendell Gilliam; Devendra M. Amatya

    2009-01-01

    Human alteration of the nitrogen cycle has led to increased riverine nitrogen loads, contributing to the eutrophication of lakes, streams, estuaries, and near-coastal oceans. These riverine nitrogen loads are usually less...

  2. Fundamental Characterization of Spanwise Loading and Trailed Wake Vortices

    DTIC Science & Technology

    2016-07-01

    the close interaction of the tip vortex with a following blade . Such vortex interactions are fundamental determinants of rotor performance, loads, and...wing loading distribution differs from a typical loading on a hovering rotor blade in that the maximum bound circulation occurs at the blade root...and not close to the tip; this is similar to a very highly twisted rotor blade , like a tilt-rotor, in hover. The wing-vortex interaction alters the

  3. Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

    PubMed Central

    Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.

    2014-01-01

    Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary PMID:25226301

  4. Uni-Directional Cell Stretching Device

    NASA Technical Reports Server (NTRS)

    Feeback, Daniel L. (Inventor); Clarke, Mark S. F. (Inventor)

    2000-01-01

    The present invention relates to an apparatus and method for applying various degrees of linear, mechanical loads on mammalian tissues, and in particular, for effecting linear stretching of tissue and simulating changes in hydrostatic pressures encountered during tissue contraction in vivo. The apparatus is useful for the study of mechanical loading in human tissue, and specifically, for permitting the evaluation of the effects of mechanical loading of skeletal or cardiac tissue and of the effects of removal of mechanical loading due to inactivity or the like, and the subsequent reapplication of load to these tissues.

  5. Changes in pelvic organ prolapse mesh mechanical properties following implantation in rats.

    PubMed

    Ulrich, Daniela; Edwards, Sharon L; Alexander, David L J; Rosamilia, Anna; Werkmeister, Jerome A; Gargett, Caroline E; Letouzey, Vincent

    2016-02-01

    Pelvic organ prolapse (POP) is a multifactorial disease that manifests as the herniation of the pelvic organs into the vagina. Surgical methods for prolapse repair involve the use of a synthetic polypropylene mesh. The use of this mesh has led to significantly higher anatomical success rates compared with native tissue repairs, and therefore, despite recent warnings by the Food and Drug Administration regarding the use of vaginal mesh, the number of POP mesh surgeries has increased over the last few years. However, mesh implantation is associated with higher postsurgery complications, including pain and erosion, with higher consecutive rates of reoperation when placed vaginally. Little is known on how the mechanical properties of the implanted mesh itself change in vivo. It is assumed that the mechanical properties of these meshes remain unchanged, with any differences in mechanical properties of the formed mesh-tissue complex attributed to the attached tissue alone. It is likely that any changes in mesh mechanical properties that do occur in vivo will have an impact on the biomechanical properties of the formed mesh-tissue complex. The objective of the study was to assess changes in the multiaxial mechanical properties of synthetic clinical prolapse meshes implanted abdominally for up to 90 days, using a rat model. Another objective of the study was to assess the biomechanical properties of the formed mesh-tissue complex following implantation. Three nondegradable polypropylene clinical synthetic mesh types for prolapse repair (Gynemesh PS, Polyform Lite, and Restorelle) and a partially degradable polypropylene/polyglecaprone mesh (UltraPro) were mechanically assessed before and after implantation (n = 5/ mesh type) in Sprague Dawley rats for 30 (Gynemesh PS, Polyform Lite, and Restorelle) and 90 (UltraPro and Polyform Lite) days. Stiffness and permanent extension following cyclic loading, and breaking load, of the preimplanted mesh types, explanted mesh-tissue complexes, and explanted meshes were assessed using a multi-axial (ball-burst) method. The 4 clinical meshes varied from each other in weight, thickness, porosity, and pore size and showed significant differences in stiffness and breaking load before implantation. Following 30 days of implantation, the mechanical properties of some mesh types altered, with significant decreases in mesh stiffness and breaking load, and increased permanent extension. After 90 days these changes were more obvious, with significant decreases in stiffness and breaking load and increased permanent extension. Similar biomechanical properties of formed mesh-tissue complexes were observed for mesh types of different preimplant stiffness and structure after 90 days implantation. This is the first study to report on intrinsic changes in the mechanical properties of implanted meshes and how these changes have an impact on the estimated tissue contribution of the formed mesh-tissue complex. Decreased mesh stiffness, strength, and increased permanent extension following 90 days of implantation increase the biomechanical contribution of the attached tissue of the formed mesh-tissue complex more than previously thought. This needs to be considered when using meshes for prolapse repair. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  6. Nano-Indentation of Aluminium Reinforced Metallic Glass Composites: A Molecular Dynamics Study

    NASA Astrophysics Data System (ADS)

    Yadav, D.; Gupta, P.; Yedla, N.

    2018-03-01

    Molecular dynamics (MD) simulations are performed for nanoindentation on metal (Al)-metallic glass (Cu50Zr50) reinforced composites to investigate the mechanical properties and the effects of volume percentage on behavior of the load-displacement curves. The interaction among Al-Cu-Zr is modelled using a EAM (Embedded Atom Method) potential. Simulation box size of 100 Å (x) × 100 Å (y) × 100 Å (z) is modelled for investigating the properties of the sintered models by altering the volume percentage on the scale of 5%-20%. Nanoindentation is done along y-direction with a spherical diamond indenter at temperature of 300 K with constant indentation speed of 100 m/s. NVT ensemble is used with a timestep of 0.002 ps. Investigations on the effect of volume percentage show that as volume percentage of Metallic Glass (MG) increases, the corresponding Load required to penetrate inside the sample also increases. As a result of this Hardness also increase as volume percentage varies from 5% to 20%.

  7. Effects of moisture, residual thermal curing stresses and mechanical load on the damage development in quasi-isotropic laminates

    NASA Technical Reports Server (NTRS)

    Kriz, R. D.; Stinchcomb, W. W.; Tenney, D. R.

    1980-01-01

    Classical laminate theory and a finite element model were used to predict stress states prior to the first formation of damage in laminates fabricated from T/300/5208. Crack patterns characteristic of the laminate in a wet or dry condition were also predicted using a shear lag model. Development of edge damage was recorded and observed during the test by transferring an image of the damage from the edge surface on to a thin acetate sheet such that the damage imprinted could be immediately viewed on a microfiche card reader. Moisture was shown to significantly alter the interior and edge dry stress states due to swelling and a reduction of elastic properties and to reduce the transverse strength in 90 deg plies. A model was developed in order to predict changes in first ply failure laminate loads due to differences in stacking sequence together with a wet or dry environmental condition.

  8. Reinforcement Strategies for Load-Bearing Calcium Phosphate Biocements

    PubMed Central

    Geffers, Martha; Groll, Jürgen; Gbureck, Uwe

    2015-01-01

    Calcium phosphate biocements based on calcium phosphate chemistry are well-established biomaterials for the repair of non-load bearing bone defects due to the brittle nature and low flexural strength of such cements. This article features reinforcement strategies of biocements based on various intrinsic or extrinsic material modifications to improve their strength and toughness. Altering particle size distribution in conjunction with using liquefiers reduces the amount of cement liquid necessary for cement paste preparation. This in turn decreases cement porosity and increases the mechanical performance, but does not change the brittle nature of the cements. The use of fibers may lead to a reinforcement of the matrix with a toughness increase of up to two orders of magnitude, but restricts at the same time cement injection for minimal invasive application techniques. A novel promising approach is the concept of dual-setting cements, in which a second hydrogel phase is simultaneously formed during setting, leading to more ductile cement–hydrogel composites with largely unaffected application properties.

  9. Skylab experiment M-171 'Metabolic Activity' - Results of the first manned mission

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.; Sawin, C. F.

    1975-01-01

    The experiment was performed to ascertain whether man's ability to perform mechanical work would be altered as a result of exposure to the weightless environment. Skylab II crewmen were exercised on a bicycle ergometer at loads approximating 25%, 50%, and 75% of their maximum oxygen uptake while their physiological responses were monitored. The results of these tests indicate that the crewmen had no significant decrement in their response to exercise during their exposure to zero gravity. Immediately postflight, however, all crewmen demonstrated an inability to perform the programmed exercise with the same metabolic effectiveness as they did both preflight and inflight. The most significant changes were elevated heart rates for the same work load and oxygen consumption (decreased oxygen pulse), decreased stroke volume, and decreased cardiac output at the same oxygen consumption level. It is apparent that the changes occurred inflight, but did not manifest themselves until the crewmen attempted to readapt to the 1-G environment.

  10. Single-source mechanical loading system produces biaxial stresses in cylinders

    NASA Technical Reports Server (NTRS)

    Flower, J. F.; Stafford, R. L.

    1967-01-01

    Single-source mechanical loading system proportions axial-to-hoop tension loads applied to cylindrical specimens. The system consists of hydraulic, pneumatic, and lever arrangements which produce biaxial loading ratios.

  11. Physical exercise induces structural alterations in the hippocampal astrocytes: exploring the role of BDNF-TrkB signaling.

    PubMed

    Fahimi, Atoossa; Baktir, Mehmet Akif; Moghadam, Sarah; Mojabi, Fatemeh S; Sumanth, Krithika; McNerney, M Windy; Ponnusamy, Ravikumar; Salehi, Ahmad

    2017-05-01

    While it has been known that physical activity can improve cognitive function and protect against neurodegeneration, the underlying mechanisms for these protective effects are yet to be fully elucidated. There is a large body of evidence indicating that physical exercise improves neurogenesis and maintenance of neurons. Yet, its possible effects on glial cells remain poorly understood. Here, we tested whether physical exercise in mice alters the expression of trophic factor-related genes and the status of astrocytes in the dentate gyrus of the hippocampus. In addition to a significant increase in Bdnf mRNA and protein levels, we found that 4 weeks of treadmill and running wheel exercise in mice, led to (1) a significant increase in synaptic load in the dentate gyrus, (2) alterations in astrocytic morphology, and (3) orientation of astrocytic projections towards dentate granule cells. Importantly, these changes were possibly linked to increased TrkB receptor levels in astrocytes. Our study suggests that astrocytes actively respond and could indeed mediate the positive effects of physical exercise on the central nervous system and potentially counter degenerative processes during aging and neurodegenerative disorders.

  12. Sudden oak death-caused changes to surface fuel loading and potential fire behavior in Douglas-fir-tanoak forests

    Treesearch

    Y.S. Valachovic; C.A. Lee; H. Scanlon; J.M. Varner; R. Glebocki; B.D. Graham; D.M. Rizzo

    2011-01-01

    We compared stand structure and fuel loading in northwestern California forests invaded by Phytophthora ramorum, the cause of sudden oak death, to assess whether the continued presence of this pathogen alters surface fuel loading and potential fire behavior in ways that may encumber future firefighting response. To attempt to account for these...

  13. Impacts of transportation infrastructure on storm water and surfaces waters in Chittenden County, Vermont, USA.

    DOT National Transportation Integrated Search

    2014-06-01

    Transportation infrastructure is a major source of stormwater runoff that can alter hydrology and : contribute significant loading of nutrients, sediment, and other pollutants to surface waters. These : increased loads can contribute to impairment of...

  14. Crosslinked elastic fibers are necessary for low energy loss in the ascending aorta.

    PubMed

    Kim, Jungsil; Staiculescu, Marius Catalin; Cocciolone, Austin J; Yanagisawa, Hiromi; Mecham, Robert P; Wagenseil, Jessica E

    2017-08-16

    In the large arteries, it is believed that elastin provides the resistance to stretch at low pressure, while collagen provides the resistance to stretch at high pressure. It is also thought that elastin is responsible for the low energy loss observed with cyclic loading. These tenets are supported through experiments that alter component amounts through protease digestion, vessel remodeling, normal growth, or in different artery types. Genetic engineering provides the opportunity to revisit these tenets through the loss of expression of specific wall components. We used newborn mice lacking elastin (Eln -/- ) or two key proteins (lysyl oxidase, Lox -/- , or fibulin-4, Fbln4 -/- ) that are necessary for the assembly of mechanically-functional elastic fibers to investigate the contributions of elastic fibers to large artery mechanics. We determined component content and organization and quantified the nonlinear and viscoelastic mechanical behavior of Eln -/- , Lox -/- , and Fbln4 -/- ascending aorta and their respective controls. We confirmed that the lack of elastin, fibulin-4, or lysyl oxidase leads to absent or highly fragmented elastic fibers in the aortic wall and a 56-97% decrease in crosslinked elastin amounts. We found that the resistance to stretch at low pressure is decreased only in Eln -/- aorta, confirming the role of elastin in the nonlinear mechanical behavior of the aortic wall. Dissipated energy with cyclic loading and unloading is increased 53-387% in Eln -/- , Lox -/- , and Fbln4 -/- aorta, indicating that not only elastin, but properly assembled and crosslinked elastic fibers, are necessary for low energy loss in the aorta. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Effects and empirical critical loads of Nitrogen for ecoregions of the United States

    USGS Publications Warehouse

    Pardo, Linda H.; Robin-Abbott, Molly J.; Fenn, Mark E.; Goodale, Christine L.; Geiser, Linda H.; Driscoll, Charles T.; Allen, Edith B.; Baron, Jill S.; Bobbink, Roland; Bowman, William D.; Clark, C M; Emmett, B.; Gilliam, Frank S; Greaver, Tara L.; Hall, Sharon J; Lilleskov, Erik A.; Liu, Lingli; Lynch, Jason A.; Nadelhoffer, Knute J; Perakis, Steven; Stoddard, John L; Weathers, Kathleen C.; Dennis, Robin L.

    2015-01-01

    Human activity in the last century has increased nitrogen (N) deposition to a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. We synthesized current research relating atmospheric N deposition to effects on terrestrial and freshwater ecosystems in the United States, and estimated associated empirical critical loads of N for several receptors: freshwater diatoms, mycorrhizal fungi, lichens, bryophytes, herbaceous plants, shrubs, and trees. Biogeochemical responses included increased N mineralization and nitrification, increased gaseous N losses, and increased N leaching. Individual species, population, and community responses included increased tissue N, physiological and nutrient imbalances, increased growth, altered root-shoot ratios, increased susceptibility to secondary stresses, altered fire regime, shifts in competitive interactions and community composition, changes in species richness and other measures of biodiversity, and increases in invasive species. The range of critical loads of nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1–39 kg N ha−1 yr−1, spanning the range of N deposition observed over most of the country. The empirical critical loads of N tend to increase in the following sequence: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees.

  16. Probabilistic Evaluation of Advanced Ceramic Matrix Composite Structures

    NASA Technical Reports Server (NTRS)

    Abumeri, Galib H.; Chamis, Christos C.

    2003-01-01

    The objective of this report is to summarize the deterministic and probabilistic structural evaluation results of two structures made with advanced ceramic composites (CMC): internally pressurized tube and uniformly loaded flange. The deterministic structural evaluation includes stress, displacement, and buckling analyses. It is carried out using the finite element code MHOST, developed for the 3-D inelastic analysis of structures that are made with advanced materials. The probabilistic evaluation is performed using the integrated probabilistic assessment of composite structures computer code IPACS. The affects of uncertainties in primitive variables related to the material, fabrication process, and loadings on the material property and structural response behavior are quantified. The primitive variables considered are: thermo-mechanical properties of fiber and matrix, fiber and void volume ratios, use temperature, and pressure. The probabilistic structural analysis and probabilistic strength results are used by IPACS to perform reliability and risk evaluation of the two structures. The results will show that the sensitivity information obtained for the two composite structures from the computational simulation can be used to alter the design process to meet desired service requirements. In addition to detailed probabilistic analysis of the two structures, the following were performed specifically on the CMC tube: (1) predicted the failure load and the buckling load, (2) performed coupled non-deterministic multi-disciplinary structural analysis, and (3) demonstrated that probabilistic sensitivities can be used to select a reduced set of design variables for optimization.

  17. Nondestructive measurement of esophageal biaxial mechanical properties utilizing sonometry

    NASA Astrophysics Data System (ADS)

    Aho, Johnathon M.; Qiang, Bo; Wigle, Dennis A.; Tschumperlin, Daniel J.; Urban, Matthew W.

    2016-07-01

    Malignant esophageal pathology typically requires resection of the esophagus and reconstruction to restore foregut continuity. Reconstruction options are limited and morbid. The esophagus represents a useful target for tissue engineering strategies based on relative simplicity in comparison to other organs. The ideal tissue engineered conduit would have sufficient and ideally matched mechanical tolerances to native esophageal tissue. Current methods for mechanical testing of esophageal tissues both in vivo and ex vivo are typically destructive, alter tissue conformation, ignore anisotropy, or are not able to be performed in fluid media. The aim of this study was to investigate biomechanical properties of swine esophageal tissues through nondestructive testing utilizing sonometry ex vivo. This method allows for biomechanical determination of tissue properties, particularly longitudinal and circumferential moduli and strain energy functions. The relative contribution of mucosal-submucosal layers and muscular layers are compared to composite esophagi. Swine thoracic esophageal tissues (n  =  15) were tested by pressure loading using a continuous pressure pump system to generate stress. Preconditioning of tissue was performed by pressure loading with the pump system and pre-straining the tissue to in vivo length before data was recorded. Sonometry using piezocrystals was utilized to determine longitudinal and circumferential strain on five composite esophagi. Similarly, five mucosa-submucosal and five muscular layers from thoracic esophagi were tested independently. This work on esophageal tissues is consistent with reported uniaxial and biaxial mechanical testing and reported results using strain energy theory and also provides high resolution displacements, preserves native architectural structure and allows assessment of biomechanical properties in fluid media. This method may be of use to characterize mechanical properties of tissue engineered esophageal constructs.

  18. Cyclic Load Effects on Long Term Behavior of Polymer Matrix Composites

    NASA Technical Reports Server (NTRS)

    Shah, A. R.; Chamis, C. C.

    1996-01-01

    A methodology to compute the fatigue life for different ratios, r, of applied stress to the laminate strength based on first ply failure criteria combined with thermal cyclic loads has been developed and demonstrated. Degradation effects resulting from long term environmental exposure and thermo-mechanical cyclic loads are considered in the simulation process. A unified time-stress dependent multi-factor interaction equation model developed at NASA Lewis Research Center has been used to account for the degradation of material properties caused by cyclic and aging loads. Effect of variation in the thermal cyclic load amplitude on a quasi-symmetric graphite/epoxy laminate has been studied with respect to the impending failure modes. The results show that, for the laminate under consideration, the fatigue life under combined mechanical and low thermal amplitude cyclic loads is higher than that due to mechanical loads only. However, as the thermal amplitude increases, the life also decreases. The failure mode changes from tensile under mechanical loads only to the compressive and shear at high mechanical and thermal loads. Also, implementation of the developed methodology in the design process has been discussed.

  19. Friction Stir Weld Failure Mechanisms in Aluminum-Armor Structures Under Ballistic Impact Loading Conditions

    DTIC Science & Technology

    2013-01-01

    REPORT Friction Stir Weld Failure Mechanisms in Aluminum -Armor Structures Under Ballistic Impact Loading Conditions 14. ABSTRACT 16. SECURITY...Stir Weld Failure Mechanisms in Aluminum -Armor Structures Under Ballistic Impact Loading Conditions M. Grujicic, B. Pandurangan, A. Arakere, C-F. Yen...K.O. Pedersen, Fracture Mechanisms of Aluminum Alloy AA7075-T651 Under Various Loading Conditions , Int. J. Impact Eng., 2010, 37, p 537–551 24. T

  20. The influence of pre-existing rib fractures on Global Human Body Models Consortium thorax response in frontal and oblique impact.

    PubMed

    Zaseck, Lauren Wood; Chen, Cong; Hu, Jingwen; Reed, Matthew P; Rupp, Jonathan

    2018-03-01

    Many post-mortem human subjects (PMHS) considered for use in biomechanical impact tests have pre-existing rib fractures (PERFs), usually resulting from cardiopulmonary resuscitation. These specimens are typically excluded from impact studies with the assumption that the fractures will alter the thoracic response to loading. We previously used the Global Human Body Models Consortium 50th percentile whole-body finite element model (GHBMC M50-O) to demonstrate that up to three lateral or bilateral PERFs do not meaningfully influence the response of the GHBMC thorax to lateral loading. This current study used the GHBMC M50-O to explore the influence of PERFs on thorax response in frontal and oblique loading. Up to six PERFs were simulated on the anterior or lateral rib regions, and the model was subjected to frontal or oblique cylindrical impactor, frontal seatbelt, or frontal seatbelt + airbag loading. Changes in thorax force-compression responses due to PERFs were generally minor, with the greatest alterations seen in models with six PERFs on one side of the ribcage. The observed changes, however, were small relative to mid-size male corridors for the loading conditions simulated. PERFs altered rib strain patterns, but the changes did not translate to changes in global thoracic response. Within the limits of model fidelity, the results suggest that PMHS with up to six PERFs may be appropriate for use in frontal or oblique impact testing. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis.

    PubMed

    Prinold, Joe A I; Mazzà, Claudia; Di Marco, Roberto; Hannah, Iain; Malattia, Clara; Magni-Manzoni, Silvia; Petrarca, Maurizio; Ronchetti, Anna B; Tanturri de Horatio, Laura; van Dijkhuizen, E H Pieter; Wesarg, Stefan; Viceconti, Marco

    2016-01-01

    Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important.

  2. The impact of uphill cycling and bicycle suspension on downhill performance during cross-country mountain biking.

    PubMed

    Macdermid, Paul W; Fink, Philip W; Miller, Matthew C; Stannard, Stephen

    2017-07-01

    Non-propulsive work demand has been linked to reduced energetic economy of cross-country mountain biking. The purpose of this study was to determine mechanical, physiological and performance differences and observe economy while riding a downhill section of a cross-country course prior to and following the metabolic "load" of a climb at race pace under two conditions (hardtail and full suspension) expected to alter vibration damping mechanics. Participants completed 1 lap of the track incorporating the same downhill section twice, under two conditions (hardtail and full suspension). Performance was determined by time to complete overall lap and specific terrain sections. Power, cadence, heart rate and oxygen consumption were sampled and logged every second while triaxial accelerometers recorded accelerations (128 Hz) to quantify vibration. No differences between performance times (P = 0.65) or power outputs (P = 0.61) were observed while physiological demand of loaded downhill riding was significantly greater (P < 0.0001) than unloaded. Full suspension decreased total vibrations experienced (P < 0.01) but had no effect on performance (P = 0.97) or physiological (P > 0.05) measures. This study showed minimal advantage of a full suspension bike in our trial, with further investigations over a full race distance warranted.

  3. Long-term effects of vertebroplasty: adjacent vertebral fractures.

    PubMed

    Baroud, Gamal; Vant, Christianne; Wilcox, Ruth

    2006-01-01

    In today's aging population, osteoporosis-related fractures are an ever-growing concern. Vertebroplasty, a promising yet cost-effective treatment for vertebral compression fractures, has an increasing role. The first vertebroplasty procedures were reported by Deramond and Galibert in France in 1987, and international interest grew with continued development of clinical techniques and augmentation materials in Europe and the United States. Initial publications and presentations at peer review meetings demonstrated 60-90% success rates in providing immediate and significant pain relief. The objective of this review is to assemble experimental and computational biomechanical research whose goal is determining and preventing the negative long-term effects ofvertebroplasty, with a specific focus on adjacent vertebral fractures. Biomechanical studies using isolated cancellous bone cylinders have shown that osteoporotic cancellous bone samples augmented by the rigid bone cement were at least 12 times stiffer and 35 times stronger than the untreated osteoporotic cancellous bone samples. The biomechanical efficacy of the procedure to repair the fractured vertebrae and prevent further collapse is determined using single-vertebra models. The strength or load-bearing capacity of a single vertebra is significantly increased following augmentation when compared to the intact strength. However, there is no dear result regarding the overall stiffness of the single vertebra, with studies reporting contradictorily that the stiffness increases, decreases, or does not significantly alter following augmentation. The effects of vertebroplasty on adjacent structures are studied via multisegment models, whose results plainly oppose the findings of the single-vertebra and intravertebral models. Here, augmentation was shown to decrease the overall segment strength by 19% when compared to the matched controls. As well, there is a significant increase in disc pressure compared to the pre-augmentation measurements. This translates to a high hydrostatic pressure adjacent to the augmented vertebra, representing the first evidence of increased loading. Computational finite element (FE) models have found that the rigid cement augmentation results in an increase in loading in the structures adjacent to the augmented vertebra. The mechanism of the increase of the loading is predicted to be the pillar effect of the rigid cement. The cement inhibits the normal endplate bulge into the augmented vertebra and thus pressurizes the adjacent disc, which subsequently increases the loading of the untreated vertebra. The mechanism for adjacent vertebral fractures is still unclear, but from experimental and computational studies, it appears that the change in mechanical loading following augmentation is responsible. The pillar effect of injected cement is hypothesized to decrease the endplate bulge in the augmented vertebra causing an increase in adjacent disc pressure that is communicated to the adjacent vertebra. To confirm the viability of the pillar effect as the responsible mechanism, endplate bulge and disc pressure should be directly measured before and after augmentation. Future studies should be concerned with quantifying the current and ideal mechanical response of the spine and subsequently developing cements that can achieve this optimum response.

  4. LAND REMEDIATION WITH BIOSOLIDS - SLUDGE MAGIC - TIME BOMB?

    EPA Science Inventory

    Addition of biosolids to soils increases the environmental loading of toxic metals (Cd, Zn, Cu, Ni, Pb, etc.) and alters the chemistry and phytoavailability of these metals. This alteration in phytoavailability associated with biosolids amended soil was recognized and utilized by...

  5. Investigation of efficiency of electric drive control system of excavator traction mechanism based on feedback on load

    NASA Astrophysics Data System (ADS)

    Kuznetsov, N. K.; Iov, I. A.; Iov, A. A.

    2018-05-01

    The article presents the results of a study of the efficiency of the electric drive control system of the traction mechanism of a dragline based on the use of feedback on load in the traction cable. The investigations were carried out using a refined electromechanical model of the traction mechanism, which took into account not only the elastic elements of the gearbox, the backlashes in it and the changes in the kinematic parameters of the mechanism during operation, but also the mechanical characteristics of the electric drive and the features of its control system. By mathematical modeling of the transient processes of the electromechanical system, it is shown that the introduction of feedback on the load in the elastic element allows one to reduce the dynamic loads in the traction mechanism and to limit the elastic oscillations of the actuating mechanism in comparison with the standard control system. Fixed as a general decrease in the dynamic load of the nodes of traction mechanism in the modes of loading and latching of the bucket, and a decrease the operating time of the mechanism at maximum load. At the same time, undesirable phenomena in the operation of the electric drive were also associated with the increase in the recovery time of the steady-state value of the speed of the actuating mechanism under certain operating conditions, which can lead to a decrease in the reliability of the mechanical part and the productivity of the traction mechanism.

  6. Reference point indentation is insufficient for detecting alterations in traditional mechanical properties of bone under common experimental conditions.

    PubMed

    Krege, John B; Aref, Mohammad W; McNerny, Erin; Wallace, Joseph M; Organ, Jason M; Allen, Matthew R

    2016-06-01

    Reference point indentation (RPI) was developed as a novel method to assess mechanical properties of bone in vivo, yet it remains unclear what aspects of bone dictate changes/differences in RPI-based parameters. The main RPI parameter, indentation distance increase (IDI), has been proposed to be inversely related to the ability of bone to form/tolerate damage. The goal of this work was to explore the relationshipre-intervention RPI measurebetween RPI parameters and traditional mechanical properties under varying experimental conditions (drying and ashing bones to increase brittleness, demineralizing bones and soaking in raloxifene to decrease brittleness). Beams were machined from cadaveric bone, pre-tested with RPI, subjected to experimental manipulation, post-tested with RPI, and then subjected to four-point bending to failure. Drying and ashing significantly reduced RPI's IDI, as well as ultimate load (UL), and energy absorption measured from bending tests. Demineralization increased IDI with minimal change to bending properties. Ex vivo soaking in raloxifene had no effect on IDI but tended to enhance post-yield behavior at the structural level. These data challenge the paradigm of an inverse relationship between IDI and bone toughness, both through correlation analyses and in the individual experiments where divergent patterns of altered IDI and mechanical properties were noted. Based on these results, we conclude that RPI measurements alone, as compared to bending tests, are insufficient to reach conclusions regarding mechanical properties of bone. This proves problematic for the potential clinical use of RPI measurements in determining fracture risk for a single patient, as it is not currently clear that there is an IDI, or even a trend of IDI, that can determine clinically relevant changes in tissue properties that may contribute to whole bone fracture resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Reference point indentation is insufficient for detecting alterations in traditional mechanical properties of bone under common experimental conditions

    PubMed Central

    Krege, John B.; Aref, Mohammad W.; McNerny, Erin; Wallace, Joseph M.; Organ, Jason M.; Allen, Matthew R.

    2016-01-01

    Reference point indentation (RPI) was developed as a novel method to assess mechanical properties of bone in vivo, yet it remains unclear what aspects of bone dictate changes/differences in RPI-based parameters. The main RPI parameter, indentation distance increase (IDI), has been proposed to be inversely related to the ability of bone to form/tolerate damage. The goal of this work was to explore the relationship between RPI parameters and traditional mechanical properties under varying experimental conditions (drying and ashing bones to increase brittleness, demineralizing bones and soaking in raloxifene to decrease brittleness). Beams were machined from cadaveric bone, pre-tested with RPI, subjected to experimental manipulation, post-tested with RPI, and then subjected to four-point bending to failure. Drying and ashing significantly reduced RPI’s IDI, as well as ultimate load (UL), and energy absorption measured from bending tests. Demineralization increased IDI with minimal change to bending properties. Ex vivo soaking in raloxifene had no effect on IDI but tended to enhance post-yield behavior at the structural level. These data challenge the paradigm of an inverse relationship between IDI and bone toughness, both through correlation analyses and in the individual experiments where divergent patterns of altered IDI and mechanical properties were noted. Based on these results, we conclude that RPI measurements alone, as compared to bending tests, are insufficient to reach conclusions regarding mechanical properties of bone. This proves problematic for the potential clinical use of RPI measurements in determining fracture risk for a single patient, as it is not currently clear that there is an IDI, or even a trend of IDI, that can determine clinically relevant changes in tissue properties that may contribute to whole bone fracture resistance. PMID:27072518

  8. 46 CFR 42.09-50 - Repairs or alterations to vessel after it has been surveyed.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Repairs or alterations to vessel after it has been surveyed. 42.09-50 Section 42.09-50 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD...-50 Repairs or alterations to vessel after it has been surveyed. (a) After any survey of the vessel...

  9. Lateral Ligament Repair and Reconstruction Restore Neither Contact Mechanics of the Ankle Joint nor Motion Patterns of the Hindfoot

    PubMed Central

    Prisk, Victor R.; Imhauser, Carl W.; O'Loughlin, Padhraig F.; Kennedy, John G.

    2010-01-01

    Background: Ankle sprains may damage both the lateral ligaments of the hindfoot and the osteochondral tissue of the ankle joint. When nonoperative treatment fails, operative approaches are indicated to restore both native motion patterns at the hindfoot and ankle joint contact mechanics. The goal of the present study was to determine the effect of lateral ligament injury, repair, and reconstruction on ankle joint contact mechanics and hindfoot motion patterns. Methods: Eight cadaveric specimens were tested with use of robotic technology to apply combined compressive (200-N) and inversion (4.5-Nm) loads to the hindfoot at 0° and 20° of plantar flexion. Contact mechanics at the ankle joint were simultaneously measured. A repeated-measures experiment was designed with use of the intact condition as control, with the other conditions including sectioned anterior talofibular and calcaneofibular ligaments, the Broström and Broström-Gould repairs, and graft reconstruction. Results: Ligament sectioning decreased contact area and caused a medial and anterior shift in the center of pressure with inversion loads relative to those with the intact condition. There were no significant differences in inversion or coupled axial rotation with inversion between the Broström repair and the intact condition; however, medial translation of the center of pressure remained elevated after the Broström repair relative to the intact condition. The Gould modification of the Broström procedure provided additional support to the hindfoot relative to the Broström repair, reducing inversion and axial rotation with inversion beyond that of intact ligaments. There were no significant differences in center-of-pressure excursion patterns between the Broström-Gould repair and the intact ligament condition, but this repair increased contact area beyond that with the ligaments intact. Graft reconstruction more closely restored inversion motion than did the Broström-Gould repair at 20° of plantar flexion but limited coupled axial rotation. Graft reconstruction also increased contact areas beyond the lateral ligament-deficient conditions but altered center-of-pressure excursion patterns relative to the intact condition. Conclusions: No lateral ankle ligament reconstruction completely restored native contact mechanics of the ankle joint and hindfoot motion patterns. Clinical Relevance: Our results provide a rationale for conducting long-term, prospective, comparative, in vivo studies to assess the impact of altered mechanics following lateral ligament injury, and its nonoperative and operative treatment, on the development of ankle osteoarthritis. PMID:20962188

  10. Tilted orthodontic micro implants: a photoelastic stress analysis.

    PubMed

    Çehreli, Seçil; Özçırpıcı, Ayça Arman; Yılmaz, Alev

    2013-10-01

    The aim of this study was to examine peri-implant stresses around orthodontic micro implants upon torque-tightening and static load application by quasi-three-dimensional photoelastic stress analysis. Self-tapping orthodontic micro implants were progressively inserted into photoelastic models at 30, 45, 70, and 90 degrees and insertion torques were measured. Stress patterns (isochromatic fringe orders) were recorded by the quasi-three-dimensional photoelastic method using a circular polariscope after insertion and 250 g static force application. Torque-tightening of implants generated peri-implant stresses. Upon insertion, 90 degree placed implants displayed the lowest and homogeneous stress distribution followed by 30, 70, and 45 degree tilted implants. Static loading did not dramatically alter stress fields around the implants tested. The highest alteration in stress distribution was observed for the 90 degree placed implant, while 70 degree tilted implant had the lowest stresses among tilted implants. Torque-tightening of orthodontic micro implants creates a stress field that is not dramatically altered after application of static lateral moderate orthodontic loads, particularly at the cervical region of tilted implants.

  11. Incomplete Loading of Sodium Lauryl Sulfate and Fasted State Simulated Intestinal Fluid Micelles Within the Diffusion Layers of Dispersed Drug Particles During Dissolution.

    PubMed

    Galipeau, Kendra; Socki, Michael; Socia, Adam; Harmon, Paul A

    2018-01-01

    Poorly water soluble drug candidates have been common in developmental pipelines over the last several decades. This has fueled considerable research around understanding how bile salt and model micelles can improve drug particle dissolution rates and human drug exposure levels. However, in the pharmaceutical context only a single mechanism of how micelles load solute has been assumed, that being the direct loading mechanism put forth by Cussler and coworkers (Am Inst Chem Eng J. 1976;22(6):1006-1012) 40 years ago. In this model, micelles load at the particle surface and will be loaded to their equilibrium loading values. More recently, Kumar and Gandhi and coworkers (Langmuir. 2003;19:4014-4026) developed a comprehensive theory of micelle solubilization which also features an indirect loading mechanism which they argue should operate in ionic surfactant systems. In this mechanism, micelles cannot directly load at the solute particle surface and thus may not reach equilibrium loading values within the particle diffusion layer. In this work, we endeavor to understand if the indirect micelle loading mechanism represents a plausible description in the pharmaceutical context. The overall data in SLS and FaSSIF systems obtained here, as well as several other previously published datasets, can be described by the indirect micelle loading mechanism. Implications for pharmaceutical development of poorly soluble compounds are discussed. Copyright © 2018. Published by Elsevier Inc.

  12. Functionalization of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds via surface heparinization for bone tissue engineering.

    PubMed

    Jiang, Tao; Khan, Yusuf; Nair, Lakshmi S; Abdel-Fattah, Wafa I; Laurencin, Cato T

    2010-06-01

    Scaffolds exhibiting biological recognition and specificity play an important role in tissue engineering and regenerative medicine. The bioactivity of scaffolds in turn influences, directs, or manipulates cellular responses. In this study, chitosan/poly(lactic acid-co-glycolic acid) (chitosan/PLAGA) sintered microsphere scaffolds were functionalized via heparin immobilization. Heparin was successfully immobilized on chitosan/PLAGA scaffolds with controllable loading efficiency. Mechanical testing showed that heparinization of chitosan/PLAGA scaffolds did not significantly alter the mechanical properties and porous structures. In addition, the heparinized chitosan/PLAGA scaffolds possessed a compressive modulus of 403.98 +/- 19.53 MPa and a compressive strength of 9.83 +/- 0.94 MPa, which are in the range of human trabecular bone. Furthermore, the heparinized chitosan/PLAGA scaffolds had an interconnected porous structure with a total pore volume of 30.93 +/- 0.90% and a median pore size of 172.33 +/- 5.89 mum. The effect of immobilized heparin on osteoblast-like MC3T3-E1 cell growth was investigated. MC3T3-E1 cells proliferated three dimensionally throughout the porous structure of the scaffolds. Heparinized chitosan/PLAGA scaffolds with low heparin loading (1.7 microg/scaffold) were shown to be capable of stimulating MC3T3-E1 cell proliferation by MTS assay and cell differentiation as evidenced by elevated osteocalcin expression when compared with nonheparinized chitosan/PLAGA scaffold and chitosan/PLAGA scaffold with high heparin loading (14.1 microg/scaffold). This study demonstrated the potential of functionalizing chitosan/PLAGA scaffolds via heparinization with improved cell functions for bone tissue engineering applications.

  13. Thermo-mechanical Properties of Upper Jurassic (Malm) Carbonate Rock Under Drained Conditions

    NASA Astrophysics Data System (ADS)

    Pei, Liang; Blöcher, Guido; Milsch, Harald; Zimmermann, Günter; Sass, Ingo; Huenges, Ernst

    2018-01-01

    The present study aims to quantify the thermo-mechanical properties of Neuburger Bankkalk limestone, an outcrop analog of the Upper Jurassic carbonate formation (Germany), and to provide a reference for reservoir rock deformation within future enhanced geothermal systems located in the Southern German Molasse Basin. Experiments deriving the drained bulk compressibility C were performed by cycling confining pressure p c between 2 and 50 MPa at a constant pore pressure p p of 0.5 MPa after heating the samples to defined temperatures between 30 and 90 °C. Creep strain was then measured after each loading and unloading stage, and permeability k was obtained after each creep strain measurement. The drained bulk compressibility increased with increasing temperature and decreased with increasing differential pressure p d = p c - p p showing hysteresis between the loading and unloading stages above 30 °C. The apparent values of the indirectly calculated Biot coefficient α ind containing contributions from inelastic deformation displayed the same temperature and pressure dependencies. The permeability k increased immediately after heating and the creep rates were also temperature dependent. It is inferred that the alteration of the void space caused by temperature changes leads to the variation of rock properties measured under isothermal conditions while the load cycles applied under isothermal conditions yield additional changes in pore space microstructure. The experimental results were applied to a geothermal fluid production scenario to constrain drawdown and time-dependent effects on the reservoir, overall, to provide a reference for the hydromechanical behavior of geothermal systems in carbonate, and more specifically, in Upper Jurassic lithologies.

  14. Intergenerational gene × environment interaction of FKBP5 and childhood maltreatment on hair steroids.

    PubMed

    Koenig, Alexandra M; Ramo-Fernández, Laura; Boeck, Christina; Umlauft, Maria; Pauly, Markus; Binder, Elisabeth B; Kirschbaum, Clemens; Gündel, Harald; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana

    2018-06-01

    The inconsistency in results of cortisol alterations after childhood maltreatment (CM) might arise due to the fact that no study so far considered the effects of environmental factors such as maltreatment load and genetic factors such as the influence of FKBP5 genotype on stress hormone regulation. This study analyzed the interaction between the single nucleotide polymorphism rs1360780 within the FKBP5 gene and the severity of maternal CM experiences (maltreatment load) on hair steroid levels of mother-infant-dyads. Hair samples of N = 474 mothers and N = 331 newborns were collected < 1 week after parturition enabling a retrospective assessment of cortisol, cortisone, and dehydroepiandrosterone (DHEA) using mass spectrometry. The sum score of the Childhood Trauma Questionnaire operationalized the maternal maltreatment load. DNA from whole blood or buccal cells was used for FKBP5 genotyping. The higher the maltreatment load, the higher maternal hair cortisol and cortisone levels in T allele carriers of FKBP5 rs1360780 were observed. Hair cortisol and DHEA levels of newborns with the T allele were reduced with an increasing maternal maltreatment load, while there was an increase of hair cortisol and DHEA in newborns homozygous for the C allele. This study is the very first uncovering a gene (FKBP5) × environment (maltreatment load) interaction on hair steroids in mothers and their offspring, indicating an intergenerational transmission of hypothalamic-pituitary-adrenal axis alterations. These results may help to explain the inconsistency in previous findings on steroid hormone alterations after chronic and traumatic stress and should be considered in future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Measuring tendon properties in mdx mice: cell viability and viscoelastic characteristics.

    PubMed

    Rizzuto, E; Musarò, A; Catizone, A; Del Prete, Z

    2009-10-16

    Muscular dystrophy is a genetic disorder of skeletal muscle characterized by progressive muscle weakness. Here we assessed whether muscle wasting affects cell viability and mechanical properties of extensor digitorum longus (EDL) and of tibialis anterior (TA) tendons from mdx dystrophic mice compared to wild type (WT) mice. mdx mice represent the classical animal model for human Duchenne muscular dystrophy, and show several signs of the pathology, including a decrease in specific force and an increase of fibrotic index. Cell viability of tendons was evaluated by histological analysis, and viscoelastic properties have been assessed by a rapid measurement protocol that allowed us to compute, at the same time, tissue complex compliance for all the frequencies of interest. Confocal microscopy and mechanical properties measurements revealed that mdx tendons, compared to WT ones, have an increase in the number of dead cells and a significant reduction in tissue elasticity for all the frequencies that were tested. These findings indicate a reduced quality of the tissue. Moreover, mdx tendons have an increase in the viscous response, indicating that during dynamic loading, they dissipate more energy compared to WT. Our results demonstrate that muscular dystrophy involves not only muscle wasting, but also alteration in the viscoelastic properties of tendons, suggesting a paracrine effect of altered skeletal muscle on tendinous tissue.

  16. Hyperosmotically induced volume change and calcium signaling in intervertebral disk cells: the role of the actin cytoskeleton.

    PubMed

    Pritchard, Scott; Erickson, Geoffrey R; Guilak, Farshid

    2002-11-01

    Loading of the spine alters the osmotic environment in the intervertebral disk (IVD) as interstitial water is expressed from the tissue. Cells from the three zones of the IVD, the anulus fibrosus (AF), transition zone (TZ), and nucleus pulposus (NP), respond to osmotic stress with altered biosynthesis through a pathway that may involve calcium (Ca(2+)) as a second messenger. We examined the hypothesis that IVD cells respond to hyperosmotic stress by increasing the concentration of intracellular calcium ([Ca(2+)](i)) through a mechanism involving F-actin. In response to hyperosmotic stress, control cells from all zones decreased in volume and cells from the AF and TZ exhibited [Ca(2+)](i) transients, while cells from the NP did not. Extracellular Ca(2+) was necessary to initiate [Ca(2+)](i) transients. Stabilization of F-actin with phalloidin prevented the Ca(2+) response in AF and TZ cells and decreased the rate of volume change in cells from all zones, coupled with an increase in the elastic moduli and apparent viscosity. Conversely, actin breakdown with cytochalasin D facilitated Ca(2+) signaling while decreasing the elastic moduli and apparent viscosity for NP cells. These results suggest that hyperosmotic stress induces volume change in IVD cells and may initiate [Ca(2+)](i) transients through an actin-dependent mechanism.

  17. Mechanisms of anterior cruciate ligament injuries in elite women's netball: a systematic video analysis.

    PubMed

    Stuelcken, Max C; Mellifont, Daniel B; Gorman, Adam D; Sayers, Mark G L

    2016-08-01

    This study involved a systematic video analysis of 16 anterior cruciate ligament (ACL) injuries sustained by elite-level netball players during televised games in order to describe the game situation, the movement patterns involved, the player's behaviour, and a potential injury mechanism. Eight of the ACL injuries were classified as "indirect contact" and eight as "non-contact". Two common scenarios were identified. In Scenario A the player was jumping to receive or intercept a pass and whilst competing for the ball experienced a perturbation in the air. As a result the player's landing was unbalanced with loading occurring predominantly on the knee of the injured side. In Scenario B the player was generally in a good position at ground contact, but then noticeably altered the alignment of the trunk before the landing was completed. This involved rotating and laterally flexing the trunk without altering the alignment of the feet. Apparent knee valgus collapse on the knee of the injured side was observed in 3/6 Scenario A cases and 5/6 Scenario B cases. Players may benefit from landing training programmes that incorporate tasks that use a ball and include decision-making components or require players to learn to cope with being unbalanced.

  18. Load-bearing capacity of screw-retained CAD/CAM-produced titanium implant frameworks (I-Bridge®2) before and after cyclic mechanical loading.

    PubMed

    Dittmer, Marc Philipp; Nensa, Moritz; Stiesch, Meike; Kohorst, Philipp

    2013-01-01

    Implant-supported screw-retained fixed dental prostheses (FDPs) produced by CAD/ CAM have been introduced in recent years for the rehabilitation of partial or total endentulous jaws. However, there is a lack of data about the long-term mechanical characteristics. The aim of this study was to investigate the failure mode and the influence of extended cyclic mechanical loading on the load-bearing capacity of these frameworks. Ten five-unit FDP frameworks simulating a free-end situation in the mandibular jaw were manufactured according to the I-Bridge®2-concept (I-Bridge®2, Biomain AB, Helsingborg, Sweden) and each was screw-retained on three differently angulated Astra Tech implants (30º buccal angulation/0º angulation/30º lingual angulation). One half of the specimens was tested for static load-bearing capacity without any further treatment (control), whereas the other half underwent five million cycles of mechanical loading with 100 N as the upper load limit (test). All specimens were loaded until failure in a universal testing machine with an occlusal force applied at the pontics. Load-displacement curves were recorded and the failure mode was macro- and microscopically analyzed. The statistical analysis was performed using a t-test (p=0.05). All the specimens survived cyclic mechanical loading and no obvious failure could be observed. Due to the cyclic mechanical loading, the load-bearing capacity decreased from 8,496 N±196 N (control) to 7,592 N±901 N (test). The cyclic mechanical loading did not significantly influence the load-bearing capacity (p=0.060). The failure mode was almost identical in all specimens: large deformations of the framework at the implant connection area were obvious. The load-bearing capacity of the I-Bridge®2 frameworks is much higher than the clinically relevant occlusal forces, even with considerably angulated implants. However, the performance under functional loading in vivo depends on additional aspects. Further studies are needed to address these aspects.

  19. Load-bearing capacity of screw-retained CAD/CAM-produced titanium implant frameworks (I-Bridge®2) before and after cyclic mechanical loading

    PubMed Central

    DITTMER, Marc Philipp; NENSA, Moritz; STIESCH, Meike; KOHORST, Philipp

    2013-01-01

    Implant-supported screw-retained fixed dental prostheses (FDPs) produced by CAD/ CAM have been introduced in recent years for the rehabilitation of partial or total endentulous jaws. However, there is a lack of data about the long-term mechanical characteristics. Objective The aim of this study was to investigate the failure mode and the influence of extended cyclic mechanical loading on the load-bearing capacity of these frameworks. Material and Methods Ten five-unit FDP frameworks simulating a free-end situation in the mandibular jaw were manufactured according to the I-Bridge®2-concept (I-Bridge®2, Biomain AB, Helsingborg, Sweden) and each was screw-retained on three differently angulated Astra Tech implants (30º buccal angulation/0º angulation/30º lingual angulation). One half of the specimens was tested for static load-bearing capacity without any further treatment (control), whereas the other half underwent five million cycles of mechanical loading with 100 N as the upper load limit (test). All specimens were loaded until failure in a universal testing machine with an occlusal force applied at the pontics. Load-displacement curves were recorded and the failure mode was macro- and microscopically analyzed. The statistical analysis was performed using a t-test (p=0.05). Results All the specimens survived cyclic mechanical loading and no obvious failure could be observed. Due to the cyclic mechanical loading, the load-bearing capacity decreased from 8,496 N±196 N (control) to 7,592 N±901 N (test). The cyclic mechanical loading did not significantly influence the load-bearing capacity (p=0.060). The failure mode was almost identical in all specimens: large deformations of the framework at the implant connection area were obvious. Conclusion The load-bearing capacity of the I-Bridge®2 frameworks is much higher than the clinically relevant occlusal forces, even with considerably angulated implants. However, the performance under functional loading in vivo depends on additional aspects. Further studies are needed to address these aspects. PMID:24037068

  20. EFFECT OF BIOSOLIDS APPLICATION ON SOIL METAL CHEMISTRY AND PHYTOAVAILABILITY

    EPA Science Inventory

    Addition of biosolids to soils increases the environmental loading of toxic metals (Cd, Zn, Cu, Ni, Pb, etc.) and alters the chemistry and phytoavailability of these metals. This alteration in phytoavailability associated with biosolids amended soil was recognized and utilized ...

  1. Towards enamel biomimetics: Structure, mechanical properties and biomineralization of dental enamel

    NASA Astrophysics Data System (ADS)

    Fong, Hanson Kwok

    Dental enamel is the most mineralized tissue in the human body. This bioceramic, composed largely of hydroxyapatite (HAp), is also one of the most durable tissues despite a lifetime of masticatory loading and bacterial attack. The biosynthesis of enamel, which occurs in physiological conditions is a complex orchestration of protein assembly and mineral formation. The resulting product is the hardest tissue in the vertebrate body with the longest and most organized arrangement of hydroxyapatite crystals known to biomineralizing systems. Detail understanding of the structure of enamel in relationship to its mechanical function and the biomineralization process will provide a framework for enamel regeneration as well as potential lessons in the design of engineering materials. The objective of this study, therefore, is twofold: (1) establish the structure-function relationship of enamel as well as the dentine-enamel junction (DEJ) and (2) determine the effect of proteins on the enamel biomineralization process. A hierarchy in the enamel structure was established by means of various microscopy techniques (e.g. SEM, TEM, AFM). Mechanical properties (hardness and elastic modulus) associated with the microstructural features were also determined by nanoindentation. Furthermore, the DEJ was found to have a width in the range of micrometers to 10s of micrometers with continuous change in structure and mechanical properties. Indentation tests and contact fatigue tests using a spherical indenter have revealed that the structural features in the enamel and the DEJ played important roles in containing crack propagation emanating from the enamel tissue. To further understand the effect of this protein on the biominerailzation process, we have studied genetically engineered animals that express altered amelogenin which lack the known self-assembly properties. This in vivo study has revealed that, without the proper self-assembly of the amelogenin protein as demonstrated by the altered amelogenin, the crystal organization of the apatite phase was severely disrupted at the nucleation stage resulting in lower mineral density at the mature stage. Consequently measurably inferior mechanical properties were found in the mature enamel grown with altered amelogenin when compared to the age matched wild-type.

  2. Mechanotransduction and the functional response of bone to mechanical strain

    NASA Technical Reports Server (NTRS)

    Duncan, R. L.; Turner, C. H.

    1995-01-01

    Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

  3. Robust Segmentation of Embayments to Encompass Exposure and Changes in Constituent Load

    EPA Science Inventory

    Nutrient and contaminant loads from the watershed, atmosphere, and seaward boundary to an embayment continually change due to human activities and alterations in the trends of natural forcing. Nevertheless, residence time (a measure of exposure) is always viewed as an unchanging ...

  4. Magnetic Bead Actuation of Saccular Hair Cells

    NASA Astrophysics Data System (ADS)

    Rowland, David; Ramunno-Johnson, Damien; Lee, Jae-Hyun; Cheon, Jinwoo; Bozovic, Dolores

    2011-11-01

    When decoupled from the overlying membrane, hair bundles of the amphibian sacculus exhibit spontaneous oscillation. To explore the dynamics of this innate motility without an imposed external load, we recorded their oscillations with a high-speed CMOS camera, and applied mechanical manipulation that minimally alters the geometry of an individual hair bundle. We present a technique that utilizes micron-sized magnetic particles to actuate the stereociliary bundle with a magnetized probe. Quasi-steady-state displacements were imposed on freely oscillating bundles. Our data indicate that deflection of the bundle affects both the frequency and the amplitude of the oscillations, with a crossing of the bifurcation that is dependent on the direction and speed of the applied offset.

  5. Obesity & osteoarthritis

    PubMed Central

    King, Lauren K.; March, Lyn; Anandacoomarasamy, Ananthila

    2013-01-01

    The most significant impact of obesity on the musculoskeletal system is associated with osteoarthritis (OA), a disabling degenerative joint disorder characterized by pain, decreased mobility and negative impact on quality of life. OA pathogenesis relates to both excessive joint loading and altered biomechanical patterns together with hormonal and cytokine dysregulation. Obesity is associated with the incidence and progression of OA of both weight-bearing and non weight-bearing joints, to rate of joint replacements as well as operative complications. Weight loss in OA can impart clinically significant improvements in pain and delay progression of joint structural damage. Further work is required to determine the relative contributions of mechanical and metabolic factors in the pathogenesis of OA. PMID:24056594

  6. Behavioral Implications of Piezoelectric Stack Actuators for Control of Micromanipulation

    NASA Technical Reports Server (NTRS)

    Goldfarb, Michael; Celanovic, Nikola

    1996-01-01

    A lumped-parameter model of a piezoelectric stack actuator has been developed to describe actuator behavior for purposes of control system analysis and design, and in particular for microrobotic applications requiring accurate position and/or force control. In addition to describing the input-output dynamic behavior, the proposed model explains aspects of non-intuitive behavioral phenomena evinced by piezoelectric actuators, such as the input-output rate-independent hysteresis and the change in mechanical stiffness that results from altering electrical load. The authors incorporate a generalized Maxwell resistive capacitor as a lumped-parameter causal representation of rate-independent hysteresis. Model formulation is validated by comparing results of numerical simulations to experimental data.

  7. Cell mechanics and immune system link up to fight infections

    NASA Astrophysics Data System (ADS)

    Ekpenyong, Andrew; Man, Si Ming; Tourlomousis, Panagiotis; Achouri, Sarra; Cammarota, Eugenia; Hughes, Katherine; Rizzo, Alessandro; Ng, Gilbert; Guck, Jochen; Bryant, Clare

    2015-03-01

    Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection.

  8. Epithelial and endothelial damage induced by mechanical ventilation modes.

    PubMed

    Suki, Béla; Hubmayr, Rolf

    2014-02-01

    The adult respiratory distress syndrome (ARDS) is a common cause of respiratory failure with substantial impact on public health. Patients with ARDS generally require mechanical ventilation, which risks further lung damage. Recent improvements in ARDS outcomes have been attributed to reductions in deforming stress associated with lung protective mechanical ventilation modes and settings. The following review details the mechanics of the lung parenchyma at different spatial scales and the response of its resident cells to deforming stress in order to provide the biologic underpinnings of lung protective care. Although lung injury is typically viewed through the lens of altered barrier properties and mechanical ventilation-associated immune responses, in this review, we call attention to the importance of heterogeneity and the physical failure of the load bearing cell and tissue elements in the pathogenesis of ARDS. Specifically, we introduce a simple elastic network model to better understand the deformations of lung regions, intra-acinar alveoli and cells within a single alveolus, and consider the role of regional distension and interfacial stress-related injury for various ventilation modes. Heterogeneity of stiffness and intercellular and intracellular stress failure are fundamental components of ARDS and their development also depends on the ventilation mode.

  9. Questa baseline and pre-mining ground-water quality investigation. 23. Quantification of mass loading from mined and unmined areas along the Red River, New Mexico

    USGS Publications Warehouse

    Kimball, Briant A.; Nordstrom, D. Kirk; Runkel, Robert L.; Vincent, Kirk R.; Verplanck, Phillip L.

    2006-01-01

    Along the course of the Red River, between the town of Red River, New Mexico, and the U.S. Geological Survey streamflow-gaging station near Questa, New Mexico, there are several catchments that contain hydrothermally altered bedrock. Some of these alteration zones have been mined and others have not, presenting an opportunity to evaluate differences that may exist in the mass loading of metals from mined and unmined sections. Such differences may help to define pre-mining conditions. Spatially detailed chemical sampling at stream and inflow sites occurred during low-flow conditions in 2001 and 2002, and during the synoptic sampling, stream discharge was calculated by tracer dilution. Discharge from most catchments, particularly those with alteration scars, occurred as ground water in large debris fans, which generally traveled downstream in an alluvial aquifer until geomorphic constraints caused it to discharge at several locations along the study reach. Locations of discharge zones were indicated by the occurrence of numerous inflows as seeps and springs. Inflows were classified into four groups, based on differences in chemical character, which ranged from near-neutral water showing no influence of mining or alteration weathering to acidic water with high concentrations of metals and sulfate. Acidic, metal-rich inflows occurred from mined and unmined areas, but the most-acidic inflow water that had the highest concentrations of metals and sulfate only occurred downstream from the mine. Locations of ground-water inflow also corresponded to substantial changes in stream chemistry and mass loading of metals and sulfate. The greatest loading occurred in the Cabin Springs, Thunder Bridge, and Capulin Canyon sections, which all occur downstream from the mine. A distinct chemical character and substantially greater loading in water downstream from the mine suggest that there could be impacts from mining that can be distinguished from the water draining from unmined areas.

  10. Intracellular pH (pHin) and cytosolic calcium ([Ca2+]cyt) regulation via ATPases: studies in cell populations, single cells, and subcellular compartments

    NASA Astrophysics Data System (ADS)

    Rojas, Jose D.; Sanka, Shankar C.; Gyorke, Sandor; Wesson, Donald E.; Minta, Akwasi; Martinez-Zaguilan, Raul

    1999-07-01

    Changes in pHin and (Ca2+)cyt are important in the signal transduction mechanisms leading to many physiological responses including cell growth, motility, secretion/exocytosis, etc. The concentrations of these ions are regulated via primary and secondary ion transporting mechanisms. In diabetes, specific pH and Ca2+ regulatory mechanism might be altered. To study these ions, we employ fluorescence spectroscopy, and cell imagin spectroscopy/confocal microscopy. pH and Ca2+ indicators are loaded in the cytosol with acetoxymethyl ester forms of dyes, and in endosomal/lysosomal (E/L) compartments by overnight incubation of cells with dextran- conjugated ion fluorescent probes. We focus on specific pH and Ca2+ regulatory systems: plasmalemmal vacuolar- type H+-ATPases (pm V-ATPases) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA). As experimental models, we employ vascular smooth muscle (VSM) and microvascular endothelial cells. We have chosen these cells because they are important in blood flow regulation and in angiogenesis. These processes are altered in diabetes. In many cell types, ion transport processes are dependent on metabolism of glucose for maximal activity. Our main findings are: (a) glycolysis coupling the activity of SERCA is required for cytosolic Ca2+ homeostasis in both VSM and microvascular endothelial cells; (b) E/L compartments are important for pH and Ca2+ regulation via H+-ATPases and SERCA, respectively; and (c) pm-V- ATPases are important for pHin regulation in microvascular endothelial cells.

  11. Self locking coupling mechanism for engaging and moving a load

    DOEpatents

    Wood, R.L.; Casamajor, A.B.; Parsons, R.E.

    1980-09-12

    A coupling mechanism for engaging and lifting a load has a housing with a guide passage for receiving a knob which is secured to the load through a neck of smaller diameter. A hollow ball in the housing has an opening which receives the knob and the ball is then turned to displace the opening from the housing passage and to cause the neck to enter a slot in the ball thereby securing the load to the coupling mechanism as elements of the housing block travel of the neck back into the opening when the ball is turned to the load holding orientation. As engagement of the load and locking of the coupling mechanism are accomplished simultaneously by the same ball motion, operation is simplified and reliability is greatly increased. The ball is preferably turned by a motor through worm gearing and the coupling mechanism may be controlled from a remote location. Among other uses, the coupling mechanism is adaptable to the handling of spent nuclear reactor fuel elements.

  12. Charge transport model in nanodielectric composites based on quantum tunneling mechanism and dual-level traps

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Guochang; Chen, George, E-mail: gc@ecs.soton.ac.uk, E-mail: sli@mail.xjtu.edu.cn; School of Electronic and Computer Science, University of Southampton, Southampton SO17 1BJ

    Charge transport properties in nanodielectrics present different tendencies for different loading concentrations. The exact mechanisms that are responsible for charge transport in nanodielectrics are not detailed, especially for high loading concentration. A charge transport model in nanodielectrics has been proposed based on quantum tunneling mechanism and dual-level traps. In the model, the thermally assisted hopping (TAH) process for the shallow traps and the tunnelling process for the deep traps are considered. For different loading concentrations, the dominant charge transport mechanisms are different. The quantum tunneling mechanism plays a major role in determining the charge conduction in nanodielectrics with high loadingmore » concentrations. While for low loading concentrations, the thermal hopping mechanism will dominate the charge conduction process. The model can explain the observed conductivity property in nanodielectrics with different loading concentrations.« less

  13. Modeling the impact of scaffold architecture and mechanical loading on collagen turnover in engineered cardiovascular tissues.

    PubMed

    Argento, G; de Jonge, N; Söntjens, S H M; Oomens, C W J; Bouten, C V C; Baaijens, F P T

    2015-06-01

    The anisotropic collagen architecture of an engineered cardiovascular tissue has a major impact on its in vivo mechanical performance. This evolving collagen architecture is determined by initial scaffold microstructure and mechanical loading. Here, we developed and validated a theoretical and computational microscale model to quantitatively understand the interplay between scaffold architecture and mechanical loading on collagen synthesis and degradation. Using input from experimental studies, we hypothesize that both the microstructure of the scaffold and the loading conditions influence collagen turnover. The evaluation of the mechanical and topological properties of in vitro engineered constructs reveals that the formation of extracellular matrix layers on top of the scaffold surface influences the mechanical anisotropy on the construct. Results show that the microscale model can successfully capture the collagen arrangement between the fibers of an electrospun scaffold under static and cyclic loading conditions. Contact guidance by the scaffold, and not applied load, dominates the collagen architecture. Therefore, when the collagen grows inside the pores of the scaffold, pronounced scaffold anisotropy guarantees the development of a construct that mimics the mechanical anisotropy of the native cardiovascular tissue.

  14. Tuning Product Selectivity for Aqueous CO2 Reduction with a Mn(bipyridine)-pyrene Catalyst Immobilized on a Carbon Nanotube Electrode

    PubMed Central

    2017-01-01

    The development of high-performance electrocatalytic systems for the controlled reduction of CO2 to value-added chemicals is a key goal in emerging renewable energy technologies. The lack of selective and scalable catalysts in aqueous solution currently hampers the implementation of such a process. Here, the assembly of a [MnBr(2,2′-bipyridine)(CO)3] complex anchored to a carbon nanotube electrode via a pyrene unit is reported. Immobilization of the molecular catalyst allows electrocatalytic reduction of CO2 under fully aqueous conditions with a catalytic onset overpotential of η = 360 mV, and controlled potential electrolysis generated more than 1000 turnovers at η = 550 mV. The product selectivity can be tuned by alteration of the catalyst loading on the nanotube surface. CO was observed as the main product at high catalyst loadings, whereas formate was the dominant CO2 reduction product at low catalyst loadings. Using UV–vis and surface-sensitive IR spectroelectrochemical techniques, two different intermediates were identified as responsible for the change in selectivity of the heterogenized Mn catalyst. The formation of a dimeric Mn0 species at higher surface loading was shown to preferentially lead to CO formation, whereas at lower surface loading the electrochemical generation of a monomeric Mn-hydride is suggested to greatly enhance the production of formate. These results emphasize the advantages of integrating molecular catalysts onto electrode surfaces for enhancing catalytic activity while allowing excellent control and a deeper understanding of the catalytic mechanisms. PMID:28885841

  15. Connecting Source with Sink: The Role of Arabidopsis AAP8 in Phloem Loading of Amino Acids1[OPEN

    PubMed Central

    Santiago, James P.; Tegeder, Mechthild

    2016-01-01

    Allocation of large amounts of nitrogen to developing organs occurs in the phloem and is essential for plant growth and seed development. In Arabidopsis (Arabidopsis thaliana) and many other plant species, amino acids represent the dominant nitrogen transport forms in the phloem, and they are mainly synthesized in photosynthetically active source leaves. Following their synthesis, a broad spectrum of the amino nitrogen is actively loaded into the phloem of leaf minor veins and transported within the phloem sap to sinks such as developing leaves, fruits, or seeds. Controlled regulation of the source-to-sink transport of amino acids has long been postulated; however, the molecular mechanism of amino acid phloem loading was still unknown. In this study, Arabidopsis AMINO ACID PERMEASE8 (AAP8) was shown to be expressed in the source leaf phloem and localized to the plasma membrane, suggesting its function in phloem loading. This was further supported by transport studies with aap8 mutants fed with radiolabeled amino acids and by leaf exudate analyses. In addition, biochemical and molecular analyses revealed alterations in leaf nitrogen pools and metabolism dependent on the developmental stage of the mutants. Decreased amino acid phloem loading and partitioning to sinks led to decreased silique and seed numbers, but seed protein levels were unchanged, demonstrating the importance of AAP8 function for sink development rather than seed quality. Overall, these results show that AAP8 plays an important role in source-to-sink partitioning of nitrogen and that its function affects source leaf physiology and seed yield. PMID:27016446

  16. Analyzing the effects of mechanical and osmotic loading on glycosaminoglycan synthesis rate in cartilaginous tissues.

    PubMed

    Gao, Xin; Zhu, Qiaoqiao; Gu, Weiyong

    2015-02-26

    The glycosaminoglycan (GAG) plays an important role in cartilaginous tissues to support and transmit mechanical loads. Many extracellular biophysical stimuli could affect GAG synthesis by cells. It has been hypothesized that the change of cell volume is a primary mechanism for cells to perceive the stimuli. Experimental studies have shown that the maximum synthesis rate of GAG is achieved at an optimal cell volume, larger or smaller than this level the GAG synthesis rate decreases. Based on the hypothesis and experimental findings in the literature, we proposed a mathematical model to quantitatively describe the cell volume dependent GAG synthesis rate in the cartilaginous tissues. Using this model, we investigated the effects of osmotic loading and mechanical loading on GAG synthesis rate. It is found our proposed mathematical model is able to well describe the change of GAG synthesis rate in isolated cells or in cartilage with variations of the osmotic loading or mechanical loading. This model is important for evaluating the GAG synthesis activity within cartilaginous tissues as well as understanding the role of mechanical loading in tissue growth or degeneration. It is also important for designing a bioreactor system with proper extracellular environment or mechanical loading for growing tissue at the maximum synthesis rate of the extracellular matrix. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Influence of Body Weight on Bone Mass, Architecture, and Turnover

    PubMed Central

    Iwaniec, Urszula T.; Turner, Russell T.

    2016-01-01

    Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

  18. The seating mechanics of head-neck modular tapers in vitro: Load-displacement measurements, moisture, and rate effects.

    PubMed

    Ouellette, Eric S; Shenoy, Aarti A; Gilbert, Jeremy L

    2018-04-01

    The mechanically assisted crevice corrosion performance of head-neck modular tapers is a significant concern in orthopedic biomaterials. Fretting crevice corrosion processes in modular tapers are thought to be influenced by a wide array of factors including seating mechanics of the junction, hence there is a need for in vitro test methods that can assess their performance. This study presented a test method to directly measure the load-displacement seating mechanics of modular tapers and used this method to compare the seating mechanics for different tapers, moisture, seating loads and seating rates. Seating mechanics were explored whereby the instantaneous load-displacement behavior of the head seating onto the neck is captured and used to define the mechanics of seating. Two distinct taper design/material combinations were assembled wet or dry using axially applied loads (500, 1,000, 2,000, and 4,000 N) at two loading rates of 100 and 10 4  N/s (n = 5 for each condition) using a servohydraulic test frame. The results showed that pull-off strength scaled with seating load and ranged between 43% and 68% of seating load depending on sample and wetness. Tapers seated wet had higher pull-off strengths (2,200 ± 300 N) than those seated dry (1,800 ± 200 N, p < 0.05). Seating mechanics (load-displacement plots) varied due to sample type and due to wetness with differences in seating energy, seating stiffness, and seating displacement. These results show the detailed mechanics of seating during assembly and provide significant insight into the complex interplay of factors associated with even "ideal" seating (axial, quasistatic) loading. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1164-1172, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. Delayed visual feedback affects both manual tracking and grip force control when transporting a handheld object.

    PubMed

    Sarlegna, Fabrice R; Baud-Bovy, Gabriel; Danion, Frédéric

    2010-08-01

    When we manipulate an object, grip force is adjusted in anticipation of the mechanical consequences of hand motion (i.e., load force) to prevent the object from slipping. This predictive behavior is assumed to rely on an internal representation of the object dynamic properties, which would be elaborated via visual information before the object is grasped and via somatosensory feedback once the object is grasped. Here we examined this view by investigating the effect of delayed visual feedback during dextrous object manipulation. Adult participants manually tracked a sinusoidal target by oscillating a handheld object whose current position was displayed as a cursor on a screen along with the visual target. A delay was introduced between actual object displacement and cursor motion. This delay was linearly increased (from 0 to 300 ms) and decreased within 2-min trials. As previously reported, delayed visual feedback altered performance in manual tracking. Importantly, although the physical properties of the object remained unchanged, delayed visual feedback altered the timing of grip force relative to load force by about 50 ms. Additional experiments showed that this effect was not due to task complexity nor to manual tracking. A model inspired by the behavior of mass-spring systems suggests that delayed visual feedback may have biased the representation of object dynamics. Overall, our findings support the idea that visual feedback of object motion can influence the predictive control of grip force even when the object is grasped.

  20. Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures

    PubMed Central

    Juhász, Tamás; Szentléleky, Eszter; Szűcs Somogyi, Csilla; Takács, Roland; Dobrosi, Nóra; Engler, Máté; Tamás, Andrea; Reglődi, Dóra; Zákány, Róza

    2015-01-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load. PMID:26230691

  1. Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Pathway Is Induced by Mechanical Load and Reduces the Activity of Hedgehog Signaling in Chondrogenic Micromass Cell Cultures.

    PubMed

    Juhász, Tamás; Szentléleky, Eszter; Somogyi, Csilla Szűcs; Takács, Roland; Dobrosi, Nóra; Engler, Máté; Tamás, Andrea; Reglődi, Dóra; Zákány, Róza

    2015-07-29

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurohormone exerting protective function during various stress conditions either in mature or developing tissues. Previously we proved the presence of PACAP signaling elements in chicken limb bud-derived chondrogenic cells in micromass cell cultures. Since no data can be found if PACAP signaling is playing any role during mechanical stress in any tissues, we aimed to investigate its contribution in mechanotransduction during chondrogenesis. Expressions of the mRNAs of PACAP and its major receptor, PAC1 increased, while that of other receptors, VPAC1, VPAC2 decreased upon mechanical stimulus. Mechanical load enhanced the expression of collagen type X, a marker of hypertrophic differentiation of chondrocytes and PACAP addition attenuated this elevation. Moreover, exogenous PACAP also prevented the mechanical load evoked activation of hedgehog signaling: protein levels of Sonic and Indian Hedgehogs and Gli1 transcription factor were lowered while expressions of Gli2 and Gli3 were elevated by PACAP application during mechanical load. Our results suggest that mechanical load activates PACAP signaling and exogenous PACAP acts against the hypertrophy inducing effect of mechanical load.

  2. An Elaborate Data Set Characterizing the Mechanical Response of the Foot

    PubMed Central

    Erdemir, Ahmet; Sirimamilla, Pavana A.; Halloran, Jason P.; van den Bogert, Antonie J.

    2010-01-01

    Background Mechanical properties of the foot are responsible for its normal function and play a role in various clinical problems. Specifically, we are interested in quantification of foot mechanical properties to assist the development of computational models for movement analysis and detailed simulations of tissue deformation. Current available data are specific to a foot region and the loading scenarios are limited to a single direction. A data set that incorporates regional response, to quantify individual function of foot components, as well as overall response, to illustrate their combined operation, does not exist. Furthermore, combined three-dimensional loading scenarios while measuring the complete three-dimensional deformation response are lacking. When combined with an anatomical image data set, development of anatomically realistic and mechanically validated models becomes possible. Therefore, the goal of this study was to record and disseminate the mechanical response of a foot specimen, supported by imaging data. Method of Approach Robotic testing was conducted at the rear foot, forefoot, metatarsal heads, and the foot as a whole. Complex foot deformations were induced by single mode loading, e.g. compression, and combined loading, e.g. compression and shear. Small and large indenters were used for heel and metatarsal head loading; an elevated platform was utilized to isolate the rear foot and forefoot; and a full platform compressed the whole foot. Three-dimensional tool movements and reaction loads were recorded simultaneously. Computed tomography scans of the same specimen were collected for anatomical reconstruction a-priori. Results Three-dimensional mechanical response of the specimen was nonlinear and viscoelastic. A low stiffness region was observed starting with contact between the tool and foot regions, increasing with loading. Loading and unloading response portrayed hysteresis. Loading range ensured capturing the toe and linear regions of the load deformation curves for the dominant loading direction, with the rates approximating those of walking. Conclusion A large data set was successfully obtained to characterize the overall as well as regional mechanical response of an intact foot specimen under single and combined loads. Medical imaging complemented the mechanical testing data to establish the potential relationship between the anatomical architecture and mechanical response, and for further development of foot models that are mechanically realistic and anatomically consistent. This combined data set has been documented and disseminated in the public domain to promote future development in foot biomechanics. PMID:19725699

  3. Influence of Altered Mass Loading on Testosterone Levels and Testicular Mass

    NASA Technical Reports Server (NTRS)

    Wang, Tommy J.; Ortiz, R. M.; Wade, C. E.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Effects of altered load on testosterone levels and testicular mass in mammals are not well defined. Two separate studies (loading;centrifuged; +2G(sub z) and unloading;hindlimb suspension;HLS) were conducted to provide a better understanding of the effects of mass loading on testosterone levels and testicular mass. Daily urine samples were collected, and testicular mass measured at the end of the study. +2G(sub z): Sprague-Dawley rats (230-250 g) were centrifuged for 12 days at +2G(sub z): 8 centrifuged (EC) and 8 off centrifuge controls (OCC). EC had lower body mass, however relative testicular mass was greater. EC exhibited an increase in excreted testosterone levels between days 2 (T2) and 6 (T6), and returned to baseline at T9. HLS: To assess the effects of unloading Sprague-Dawley rats (125-150 g) were studied for 12 days: 10 suspended (Exp) and 10 ambulatory (Ctl). Exp had lower body mass during the study, with reduced absolute and relative testicular mass. Exp demonstrated lower excreted testosterone levels from T5-T12. Conclusions: Loading appears to stimulate anabolism, as opposed to unloading, as indicated by greater relative testicular mass and excreted testosterone levels. Reported changes in muscle mass during loading and unloading coincide with similar changes in excreted testosterone levels.

  4. Load dependence of left ventricular contraction and relaxation. Effects of caffeine.

    PubMed

    Leite-Moreira, A F; Correia-Pinto, J; Gillebert, T C

    1999-08-01

    Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 +/- 1.1% of peak isovolumetric LVP at baseline and at lower loads, at 77.6 +/- 1.2%, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant tau by 238 +/- 70% at baseline and only by 155 +/- 44% after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.

  5. The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice.

    PubMed

    Boly, Chantal A; Eringa, Etto C; Bouwman, R Arthur; van den Akker, Rob F P; de Man, Frances S; Schalij, Ingrid; Loer, Stephan A; Boer, Christa; van den Brom, Charissa E

    2016-09-20

    While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to improve intraoperative myocardial performance. In this experimental study we investigated whether mild adiposity without metabolic alterations is already associated with cardiometabolic dysfunction during anesthesia, mechanical ventilation and surgery and whether these myocardial alterations can be neutralized by intraoperative insulin treatment. Mice were fed a western (WD) or control diet (CD) for 4 weeks. After metabolic profiling, mice underwent general anesthesia, mechanical ventilation and surgery. Cardiac function was determined with echocardiography and left-ventricular pressure-volume analysis. Myocardial perfusion was determined with contrast-enhanced echocardiography. WD-fed mice were subsequently treated with insulin by hyperinsulinemic euglycemic clamping followed by the same measurements of cardiac function and perfusion. Western-type diet feeding led to a 13 % increase in bodyweight, (p < 0.0001) and increased adipose tissue mass, without metabolic alterations. Despite this mild phenotype, WD-fed mice had decreased systolic and diastolic function (end-systolic elastance was 2.0 ± 0.5 versus 4.1 ± 2.4 mmHg/μL, p = 0.01 and diastolic beta was 0.07 ± 0.03 versus 0.04 ± 0.01 mmHg/μL, p = 0.02) compared to CD-fed mice. Ventriculo-arterial coupling and myocardial perfusion were decreased by 48 % (p = 0.003) and 43 % (p = 0.03) respectively. Insulin treatment in WD-fed mice improved echo-derived systolic function (fractional shortening 42 ± 5 % to 46 ± 3, p = 0.05), likely due to decreased afterload, but there was no effect on load-independent measures of systolic function or myocardial perfusion. However, there was a trend towards improved diastolic function after insulin treatment (43 % improvement, p = 0.05) in WD-fed mice. Mild adiposity without metabolic alterations already affected cardiac function and perfusion during anesthesia, mechanical ventilation and surgery in mice. Intraoperative insulin may be beneficial to reduce afterload and enhance intraoperative ventricular relaxation, but not to improve ventricular contractility or myocardial perfusion.

  6. Hydrostatic self-aligning axial/torsional mechanism

    DOEpatents

    O'Connor, Daniel G.; Gerth, Howard L.

    1990-01-01

    The present invention is directed to a self-aligning axial/torsional loading mechanism for testing the strength of brittle materials which are sensitive to bending moments. Disposed inside said self-aligning loading mechanism is a frictionless hydrostatic ball joint with a flexure ring to accommodate torsional loads through said ball joint.

  7. Load theory of selective attention and cognitive control.

    PubMed

    Lavie, Nilli; Hirst, Aleksandra; de Fockert, Jan W; Viding, Essi

    2004-09-01

    A load theory of attention in which distractor rejection depends on the level and type of load involved in current processing was tested. A series of experiments demonstrates that whereas high perceptual load reduces distractor interference, working memory load or dual-task coordination load increases distractor interference. These findings suggest 2 selective attention mechanisms: a perceptual selection mechanism serving to reduce distractor perception in situations of high perceptual load that exhaust perceptual capacity in processing relevant stimuli and a cognitive control mechanism that reduces interference from perceived distractors as long as cognitive control functions are available to maintain current priorities (low cognitive load). This theory resolves the long-standing early versus late selection debate and clarifies the role of cognitive control in selective attention. ((c) 2004 APA, all rights reserved)

  8. EFFECT OF BIOSOLIDS APPLICATION ON SOIL METAL CHEMISTRY AND PHYTOAVAILABILITY (LAKE BUENA VISTA, FL)

    EPA Science Inventory

    Addition of biosolids to soils increases the environmental loading of toxic metals (Cd, Zn, Cu, Ni, Pb, etc.) and alters the chemistry and phytoavailability of these metals. This alteration in phytoavailability associated with biosolids amended soil was recognized and utilized ...

  9. Preparation for Testing a Multi-Bay Box Subjected to Combined Loads

    NASA Technical Reports Server (NTRS)

    Rouse, Marshall; Jegley, Dawn

    2015-01-01

    The COmbined Loads Test System (COLTS) facility at NASA Langley Research Center provides a test capability to help develop validated structures technologies. The test machine was design to accommodate a range of fuselage structures and wing sections and subject them to both quasistatic and cyclic loading conditions. The COLTS facility is capable of testing fuselage barrels up to 4.6 m in diameter and 13.7 m long with combined mechanical, internal pressure, and thermal loads. The COLTS facility is currently being prepared to conduct a combined mechanical and pressure loading for a multi-bay pressure box to experimentally verify the structural performance of a composite structure which is 9.1 meters long and representative of a section of a hybrid wing body fuselage section in support of the Environmentally Responsible Aviation Project at NASA. This paper describes development of the multi-bay pressure box test using the COLTS facility. The multi-bay test article will be subjected to mechanical loads and internal pressure loads up to design ultimate load. Mechanical and pressure loads will be applied independently in some tests and simultaneously in others.

  10. Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium.

    PubMed

    Cork, Karlene M; Thoreson, Wallace B

    2014-05-01

    Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (C m) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging <200 ms. We manipulated Ca2+ influx and the amount of vesicle release by altering the duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels.

  11. Variability of Jump Kinetics Related to Training Load in Elite Female Basketball.

    PubMed

    Legg, Jan; Pyne, David B; Semple, Stuart; Ball, Nick

    2017-11-04

    The purpose of this study was to quantify changes in jump performance and variability in elite female basketballers. Junior and senior female representative basketball players ( n = 10) aged 18 ± 2 years participated in this study. Countermovement jump (CMJ) data was collected with a Gymaware™ optical encoder at pre-, mid-, and post-season time points across 10 weeks. Jump performance was maintained across the course of the full season (from pre to post). Concentric peak velocity, jump height, and dip showed the most stability from pre- to post-season, with the %CV ranging from 5.6⁻8.9%. In the period of the highest training load (mid-season), the variability of within-subject performance was reduced by approximately 2⁻4% in all measures except for jump height. Altered jump mechanics through a small (0.26 effect size) increase in dip were evident at mid-season, suggesting that CMJ analysis is useful for coaches to use as an in-season monitoring tool. The highest coefficient of variation (8⁻22%CV) in inter-set scores in all measures except eccentric peak velocity also occurred mid-season. It appears that in-season load not only impairs jump performance, but also movement variability in basketball players.

  12. Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium

    PubMed Central

    CORK, KARLENE M.; THORESON, WALLACE B.

    2015-01-01

    Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (Cm) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging <200 ms. We manipulated Ca2+ influx and the amount of vesicle release by altering the duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels. PMID:24735554

  13. Mechanical loading increases detection of estrogen receptor-alpha in osteocytes and osteoblasts despite chronic energy restriction.

    PubMed

    Swift, Sibyl N; Swift, Joshua M; Bloomfield, Susan A

    2014-12-01

    Estrogen receptor-α (ER-α) is an important mediator of the bone response to mechanical loading. We sought to determine whether restricting dietary energy intake by 40% limits the bone formation rate (BFR) response to mechanical loading (LOAD) by downregulating ER-α-expressing osteocytes, or osteoblasts, or both. Female rats (n = 48, 7 mo old) were randomized to ADLIB-SHAM and ADLIB-LOAD groups fed AIN-93M purified diet ad libitum or to ER40-SHAM and ER40-LOAD groups fed modified AIN-93M with 40% less energy (100% of all other nutrients). After 12 wk, LOAD rats were subjected to a muscle contraction protocol three times every third day. ER40 produced lower proximal tibia bone volume (-22%), trabecular thickness (-14%), and higher trabecular separation (+127%) in SHAM but not LOAD rats. ER40 rats exhibited reductions in mineral apposition rate, but not percent mineralizing surface or BFR. LOAD induced similar relative increases in these kinetic measures of osteoblast activity/recruitment in both diet groups., but absolute values for ER40 LOAD rats were lower vs. ADLIB-LOAD. There were fourfold and eightfold increases in proportion of estrogen receptor-α protein-positive osteoblast and osteocytes, respectively, in LOAD vs. SHAM rats, with no effect of ER40. These data suggest that a brief period of mechanical loading significantly affects estrogen receptor-α in cancellous bone osteoblasts and osteocytes. Chronic energy restriction does result in lower absolute values in indices of osteoblast activity after mechanical loading, but not by a smaller increment relative to unloaded bones; this change is not explained by an associated downregulation of ER-α in osteoblasts or osteocytes.

  14. Modeling Historical and Projected Future Atmospheric Nitrogen Loading to the Chesapeake Bay Watershed

    EPA Science Inventory

    Land use and climate change are expected to alter key processes in the Chesapeake Bay watershed and can potentially exacerbate the impact of excess nitrogen. Atmospheric sources are one of the largest loadings of nitrogen to the Chesapeake Bay watershed. In this study, we explore...

  15. Carbohydrate Loading.

    ERIC Educational Resources Information Center

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  16. Nitrogen Bsalance for a Plantation Forest Drainage Canal on the North Carolina Coastal Plain

    USDA-ARS?s Scientific Manuscript database

    Human alteration of the nitrogen cycle has led to increased riverine nitrogen loads, contributing to the eutrophication of lakes, streams, estuaries, and near-coastal oceans. These riverine nitrogen loads are usually less than the total nitrogen inputs to the system, indicating nitrogen removal duri...

  17. Sclerostin's role in bone's adaptive response to mechanical loading.

    PubMed

    Galea, Gabriel L; Lanyon, Lance E; Price, Joanna S

    2017-03-01

    Mechanical loading is the primary functional determinant of bone mass and architecture, and osteocytes play a key role in translating mechanical signals into (re)modelling responses. Although the precise mechanisms remain unclear, Wnt signalling pathway components, and the anti-osteogenic canonical Wnt inhibitor Sost/sclerostin in particular, play an important role in regulating bone's adaptive response to loading. Increases in loading-engendered strains down-regulate osteocyte sclerostin expression, whereas reduced strains, as in disuse, are associated with increased sclerostin production and bone loss. However, while sclerostin up-regulation appears to be necessary for the loss of bone with disuse, the role of sclerostin in the osteogenic response to loading is more complex. While mice unable to down-regulate sclerostin do not gain bone with loading, Sost knockout mice have an enhanced osteogenic response to loading. The molecular mechanisms by which osteocytes sense and transduce loading-related stimuli into changes in sclerostin expression remain unclear but include several, potentially interlinked, signalling cascades involving periostin/integrin, prostaglandin, estrogen receptor, calcium/NO and Igf signalling. Deciphering the mechanisms by which changes in the mechanical environment regulate sclerostin production may lead to the development of therapeutic strategies that can reverse the skeletal structural deterioration characteristic of disuse and age-related osteoporosis and enhance bones' functional adaptation to loading. By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Prediction of risk of fracture in the tibia due to altered bone mineral density distribution resulting from disuse: a finite element study.

    PubMed

    Gislason, Magnus K; Coupaud, Sylvie; Sasagawa, Keisuke; Tanabe, Yuji; Purcell, Mariel; Allan, David B; Tanner, K Elizabeth

    2014-02-01

    The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions - compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.

  19. Probing collagen-enzyme mechanochemistry in native tissue with dynamic, enzyme-induced creep

    PubMed Central

    Zareian, Ramin; Church, Kelli P.; Saeidi, Nima; Flynn, Brendan P.; Beale, John W.; Ruberti, Jeffrey W.

    2012-01-01

    Mechanical strain or stretch of collagen has been shown to be protective of fibrils against both thermal and enzymatic degradation. The details of this mechanochemical relationship could change our understanding of load-bearing tissue formation, growth, maintenance and disease in vertebrate animals. However, extracting a quantitative relationship between strain and the rate of enzymatic degradation is extremely difficult in bulk tissue due to confounding diffusion effects. In this investigation, we develop a dynamic, enzyme-induced creep assay and diffusion/reaction rate scaling arguments to extract a lower bound on the relationship between strain and the cutting rate of bacterial collagenase (BC) at low strains. The assay method permits continuous, forced probing of enzyme-induced strain which is very sensitive to degradation rate differences between specimens at low initial strain. The results, obtained on uniaxially-loaded strips of bovine corneal tissue (0.1, 0.25 or 0.5 N), demonstrate that small differences in strain alter the enzymatic cutting rate of the BC substantially. It was estimated that a change in tissue elongation of only 1.5% (at ~5% strain) reduces the maximum cutting-rate of the enzyme by more than half. Estimation of the average load per monomer in the tissue strips indicates that this protective “cutoff” occurs when the collagen monomers are transitioning from an entropic to an energetic mechanical regime. The continuous tracking of the enzymatic cleavage rate as a function of strain during the initial creep response indicates that the decrease in the cleavage rate of the BC is non-linear (initially-steep between 4.5 and 6.5% then flattens out from 6.5–9.5%). The high sensitivity to strain at low strain implies that even lightly-loaded collagenous tissue may exhibit significant strain-protection. The dynamic, enzyme-induced creep assay described herein has the potential to permit the rapid characterization of collagen/enzyme mechanochemistry in many different tissue types. PMID:20429513

  20. Investigation of microstructural alterations in M50 and 52100 steel using nanoindentation

    NASA Astrophysics Data System (ADS)

    Paulson, Kristin R.

    Bearing steels are used in rolling elements and are designed to withstand heavy loads for an extended period of time. At the end of life, microstructural alterations within the material have been observed and are linked to failure. In this study, a three ball-on-rod fatigue tester was used to test M50 and 52100 steel cylindrical rods at differing loads of 4.0 GPa, 4.5 GPa, and 5.0 GPa and in lubricated and unlubricated conditions to 108 cycles in an attempt to produce microstructural alterations. Microstructural alterations characterized as butterflies were observed and investigated further in two M50 samples that were tested at 4.5 GPa to 10 8 cycles in the lubricated and unlubricated condition. Microstructural alterations characterized as dark etching regions (DER), and white etching bands (WEBs) were not observed. Additionally, hardness was investigated cross sectionally as a function of depth and location within the wear track produced by the fatigue test. No conclusive evidence was derived from the hardness measurements as a function of depth in relation to the formation of microstructural alterations or the stress experienced subsurface within the material. Hardness measurements performed specifically within a butterfly wing, however, returned hardness values significantly higher than the matrix hardness values.

  1. Combination of Heel-strike like Mechanical Loading with Deproteinized Cancellous Bone Scaffold Implantation to Repair Segmental Bone Defects in Rabbits.

    PubMed

    Huang, Guofeng; Liu, Guojun; Zhang, Feng; Gao, Jianting; Wang, Jiangze; Chen, Qi; Wu, Benwen; Ding, Zhenqi; Cai, Taoyi

    2017-01-01

    Under physiological conditions bone defects often occur at mechanical load bearing sites and bone substitutes used for regeneration should be similarly subjected to mechanical loading stress. In this study, we investigated whether a novel heel-strike like mechanical loading method can be used as a complementary therapy to promote bone regeneration following bone substitute grafting. To test this, three groups of rabbits with segmental bone defects in the tibia were implanted with bovine deproteinized cancellous bone scaffold (DCBS), with one group also receiving heel-strike like mechanical loading generated by a rap stress stimulator. From weeks 4-12 post-operation X-ray and micro-CT scanning showed that rabbits receiving combination therapy had significantly more callus at the bone defect. Moreover, bone defects in the combination group were completely replaced with new bone at week 12, while the DCBS implantation alone group healed only partially and rabbits receiving neither DCBS nor mechanical loading developed only small calluses throughout the observation period. Analysis of micro-CT scanning results demonstrated that new bone density in the combination group was significantly higher than the DCBS only group at weeks 4 and 12 ( p <0.05). H&E staining results also indicated a significantly higher percentage of new bone in the bone defect area and a lower percentage of residual scaffold in the combination group compared to the DCBS only group ( p <0.05). Thus, this heel-strike like mechanical loading method appears to accelerate bone regeneration following substitute implantation by restoring a local mechanical loading environment in segmental bone defects.

  2. In vitro and in silico investigations of disc nucleus replacement

    PubMed Central

    Reitmaier, Sandra; Shirazi-Adl, Aboulfazl; Bashkuev, Maxim; Wilke, Hans-Joachim; Gloria, Antonio; Schmidt, Hendrik

    2012-01-01

    Currently, numerous hydrogels are under examination as potential nucleus replacements. The clinical success, however, depends on how well the mechanical function of the host structure is restored. This study aimed to evaluate the extent to and mechanisms by which surgery for nucleus replacements influence the mechanical behaviour of the disc. The effects of an annulus defect with and without nucleus replacement on disc height and nucleus pressure were measured using 24 ovine motion segments. The following cases were considered: intact; annulus incision repaired by suture and glue; annulus incision with removal and re-implantation of nucleus tissue repaired by suture and glue or plug. To identify the likely mechanisms observed in vitro, a finite-element model of a human disc (L4–L5) was employed. Both studies were subjected to physiological cycles of compression and recovery. A repaired annulus defect did not influence the disc behaviour in vitro, whereas additional nucleus removal and replacement substantially decreased disc stiffness and nucleus pressure. Model predictions demonstrated the substantial effects of reductions in replaced nucleus water content, bulk modulus and osmotic potential on disc height loss and pressure, similar to measurements. In these events, the compression load transfer in the disc markedly altered by substantially increasing the load on the annulus when compared with the nucleus. The success of hydrogels for nucleus replacements is not only dependent on the implant material itself but also on the restoration of the environment perturbed during surgery. The substantial effects on the disc response of disruptions owing to nucleus replacements can be simulated by reduced nucleus water content, elastic modulus and osmotic potential. PMID:22337630

  3. What quantitative mechanical loading stimulates in vitro cultivation best?

    PubMed

    Natenstedt, Jerry; Kok, Aimee C; Dankelman, Jenny; Tuijthof, Gabrielle Jm

    2015-12-01

    Articular cartilage has limited regeneration capacities. One of the factors that appear to affect the in vitro cultivation of articular cartilage is mechanical stimulation. So far, no combination of parameters has been identified that offers the best results. The goal is to review the literature in search of the best available set of quantitative mechanical stimuli that lead to optimal in vitro cultivation.The databases Scopus and PubMed were used to survey the literature, and strict in- and exclusion criteria were applied regarding the presence of quantitative data. The review was performed by studying the type of loading (hydrostatic compression or direct compression), the loading magnitude, the frequency and the loading regime (duration of the loading) in comparison to quantitative evidence of cartilage quality response (cellular, signaling and mechanical).Thirty-three studies met all criteria of which 8 studied human, 20 bovine, 2 equine, 1 ovine, 1 porcine and 1 canine cells using four different types of cultivated constructs. Six studies investigated loading magnitude within the same setup, three studies the frequency, and seven the loading regime. Nine studies presented mechanical tissue response. The studies suggest that a certain threshold exits for enhanced cartilage in vitro cultivation of explants (>20 % strain and 0.5 Hz), and that chondrocyte-seeded cultivated constructs show best results when loaded with physiological mechanical stimuli. That is a loading pressure between 5-10 MPa and a loading frequency of 1 Hz exerted at intermittent intervals for a period of a week or longer. Critical aspects remain to be answered for translation into in vivo therapies.

  4. Mechanical scale and load cell underwater weighing: a comparison of simultaneous measurements and the reliability of methods.

    PubMed

    Moon, Jordan R; Stout, Jeffrey R; Walter, Ashley A; Smith, Abbie E; Stock, Matt S; Herda, Trent J; Sherk, Vanessa D; Young, Kaelin C; Lockwood, Christopher M; Kendall, Kristina L; Fukuda, David H; Graef, Jennifer L; Cramer, Joel T; Beck, Travis W; Esposito, Enrico N

    2011-03-01

    Both load cell and mechanical scale-based hydrostatic weighing (HW) systems are used for the measurement of underwater weight. However, there has been no direct comparison of the 2 methods. The purpose of the current investigation was to simultaneously compare a load cell and mechanical scale for use in HW. Twenty-seven men and women (mean ± SD, age: 22 ± 2 years) participated in the 2-day investigation. Each subject completed 2 HW assessments 24 hours apart. Single-day comparisons of all trials for both days revealed no significant difference between the mechanical scale and the load cell (mean difference < 0.016 kg, p > 0.05). True underwater weight values were not significantly different between methods for either days (mean difference < 0.014 kg, p > 0.05) and accounted for a mean difference in percent fat (%FAT) of <0.108%. The 95% limits of agreement indicated a maximum difference between methods of 0.53% FAT. Both methods produced similar reliability SEM values (mechanical SEM < 0.72%FAT, load cell SEM < 0.75%FAT). In conclusion, there was no difference between mechanical scale and load cell measurements of underwater weights and the added precision of the load cell only marginally (<0.16%FAT) improved day-to-day reliability. Either a mechanical scale or load cell can be used for HW with similar accuracy and reliability in young adults with a body mass index of 18.7-34.4 (5-25%FAT).

  5. Load measurement system with load cell lock-out mechanism

    NASA Technical Reports Server (NTRS)

    Le, Thang; Carroll, Monty; Liu, Jonathan

    1995-01-01

    In the frame work of the project Shuttle Plume Impingement Flight Experiment (SPIFEX), a Load Measurement System was developed and fabricated to measure the impingement force of Shuttle Reaction Control System (RCS) jets. The Load Measurement System is a force sensing system that measures any combination of normal and shear forces up to 40 N (9 lbf) in the normal direction and 22 N (5 lbf) in the shear direction with an accuracy of +/- 0.04 N (+/- 0.01 lbf) Since high resolution is required for the force measurement, the Load Measurement System is built with highly sensitive load cells. To protect these fragile load cells in the non-operational mode from being damaged due to flight loads such as launch and landing loads of the Shuttle vehicle, a motor driven device known as the Load Cell Lock-Out Mechanism was built. This Lock-Out Mechanism isolates the load cells from flight loads and re-engages the load cells for the force measurement experiment once in space. With this highly effective protection system, the SPIFEX load measurement experiment was successfully conducted on STS-44 in September 1994 with all load cells operating properly and reading impingement forces as expected.

  6. 24 CFR 3285.903 - Permits, alterations, and on-site structures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... live and dead loads, unless the structure, including any attached garage, carport, deck, and porch, is... structures. 3285.903 Section 3285.903 Housing and Urban Development Regulations Relating to Housing and Urban... Manufacturer's Installation Instructions § 3285.903 Permits, alterations, and on-site structures. It is...

  7. 24 CFR 3285.903 - Permits, alterations, and on-site structures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... live and dead loads, unless the structure, including any attached garage, carport, deck, and porch, is... structures. 3285.903 Section 3285.903 Housing and Urban Development Regulations Relating to Housing and Urban... Manufacturer's Installation Instructions § 3285.903 Permits, alterations, and on-site structures. It is...

  8. 24 CFR 3285.903 - Permits, alterations, and on-site structures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... live and dead loads, unless the structure, including any attached garage, carport, deck, and porch, is... structures. 3285.903 Section 3285.903 Housing and Urban Development Regulations Relating to Housing and Urban... Manufacturer's Installation Instructions § 3285.903 Permits, alterations, and on-site structures. It is...

  9. 24 CFR 3285.903 - Permits, alterations, and on-site structures.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... live and dead loads, unless the structure, including any attached garage, carport, deck, and porch, is... structures. 3285.903 Section 3285.903 Housing and Urban Development Regulations Relating to Housing and Urban... Manufacturer's Installation Instructions § 3285.903 Permits, alterations, and on-site structures. It is...

  10. ALTERATION OF SOIL METAL CHEMISTRY AND PHYTOAVAILABILITY ASSOCIATED WITH BIOSOLIDS APPLICATION (ABSTRACT)

    EPA Science Inventory

    Biosolids are a complex mixture which contain both inorganic and organic adsorbents. Thus, addition of biosolids to soil not only increases the environmental loading of toxic metals (Cd, Zn, Cu, Ni, Pb, etc.) it alters the phytoavailability of these metals. This reduction in ph...

  11. Chain-loaded variable resistance warm-up improves free-weight maximal back squat performance.

    PubMed

    Mina, Minas A; Blazevich, Anthony J; Giakas, Giannis; Seitz, Laurent B; Kay, Anthony D

    2016-11-01

    The acute influence of chain-loaded variable resistance exercise on subsequent free-weight one-repetition maximum (1-RM) back squat performance was examined in 16 recreationally active men. The participants performed either a free-weight resistance (FWR) or chain-loaded resistance (CLR) back squat warm-up at 85% 1-RM on two separate occasions. After a 5-min rest, the participants attempted a free-weight 1-RM back squat; if successful, subsequent 5% load additions were made until participants failed to complete the lift. During the 1-RM trials, 3D knee joint kinematics and knee extensor and flexor electromyograms (EMG) were recorded simultaneously. Significantly greater 1-RM (6.2 ± 5.0%; p < .01) and mean eccentric knee extensor EMG (32.2 ± 6.7%; p < .01) were found after the CLR warm-up compared to the FWR condition. However, no difference (p > .05) was found in concentric EMG, eccentric or concentric knee angular velocity, or peak knee flexion angle. Performing a CLR warm-up enhanced subsequent free-weight 1-RM performance without changes in knee flexion angle or eccentric and concentric knee angular velocities; thus a real 1-RM increase was achieved as the mechanics of the lift were not altered. These results are indicative of a potentiating effect of CLR in a warm-up, which may benefit athletes in tasks where high-level strength is required.

  12. Effects of medial meniscal posterior horn avulsion and repair on meniscal displacement.

    PubMed

    Hein, Christopher N; Deperio, Jennifer Gurske; Ehrensberger, Mark T; Marzo, John M

    2011-06-01

    Medial meniscal posterior root avulsion (MMRA) leads to deleterious alteration of medial joint compartment loading profiles and increased risk of medial degenerative changes. Surgical repair restores more normal biomechanics to the knee. Our hypothesis is that MMRA will cause medial meniscal (MM) extrusion and gap formation between the root attachment site and MM. Meniscal root repair will restore the ability of the meniscus to resist extrusion, and reduce gap formation at the defect. Seven fresh frozen human cadaveric knees were dissected and mechanically loaded using a servo-hydraulic load frame (MTS ®) with 0 and 1800 N. The knees were tested under three conditions: native, avulsed, and repaired. Four measurements were obtained: meniscal displacement anteriorly, medially, posteriorly, and gap distance between the root attachment site and MM after transection and repair. The medial displacement of the avulsed MM (3.28 mm) was significantly greater (p < 0.001) than the native knee (1.60mm) and repaired knee (1.46 mm). Gap formation is significantly larger in the avulsed compared to repaired state at 0 (p < 0.02) and 1800N (p < 0.02) and also larger with loading in both avulsed (p < 0.05) and repaired (p < 0.02) conditions. Therefore, MMRA results in MM extrusion from the joint and gap formation between the MM root and the MM. Subsequent surgical repair reduces meniscal displacement and gap formation at the defect. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Shape memory-based actuators and release mechanisms therefrom

    NASA Technical Reports Server (NTRS)

    Vaidyanathan, Rajan (Inventor); Snyder, Daniel W. (Inventor); Schoenwald, David K. (Inventor); Lam, Nhin S. (Inventor); Watson, Daniel S. (Inventor); Krishnan, Vinu B. (Inventor); Noebe, Ronald D. (Inventor)

    2012-01-01

    SM-based actuators (110) and release mechanisms (100) therefrom and systems (500) including one or more release mechanisms (100). The actuators (110) comprise a SM member (118) and a deformable member (140) mechanically coupled to the SM member (118) which deforms upon a shape change of the SM member triggered by a phase transition of the SM member. A retaining element (160) is mechanically coupled to the deformable member (140), wherein the retaining element (160) moves upon the shape change. Release mechanism (100) include an actuator, a rotatable mechanism (120) including at least one restraining feature (178) for restraining rotational movement of the retaining element (160) before the shape change, and at least one spring (315) that provides at least one locked spring-loaded position when the retaining element is in the restraining feature and at least one released position that is reached when the retaining element is in a position beyond the restraining feature (178). The rotatable mechanism (120) includes at least one load-bearing protrusion (310). A hitch (400) is for mechanically coupling to the load, wherein the hitch is supported on the load bearing protrusion (310) when the rotatable mechanism is in the locked spring-loaded position.

  14. A load-based mechanism for inter-leg coordination in insects

    PubMed Central

    2017-01-01

    Animals rely on an adaptive coordination of legs during walking. However, which specific mechanisms underlie coordination during natural locomotion remains largely unknown. One hypothesis is that legs can be coordinated mechanically based on a transfer of body load from one leg to another. To test this hypothesis, we simultaneously recorded leg kinematics, ground reaction forces and muscle activity in freely walking stick insects (Carausius morosus). Based on torque calculations, we show that load sensors (campaniform sensilla) at the proximal leg joints are well suited to encode the unloading of the leg in individual steps. The unloading coincides with a switch from stance to swing muscle activity, consistent with a load reflex promoting the stance-to-swing transition. Moreover, a mechanical simulation reveals that the unloading can be ascribed to the loading of a specific neighbouring leg, making it exploitable for inter-leg coordination. We propose that mechanically mediated load-based coordination is used across insects analogously to mammals. PMID:29187626

  15. Ovarian control of nectar collection in the honey bee (Apis mellifera).

    PubMed

    Siegel, Adam J; Freedman, Colin; Page, Robert E

    2012-01-01

    Honey bees are a model system for the study of division of labor. Worker bees demonstrate a foraging division of labor (DOL) by biasing collection towards carbohydrates (nectar) or protein (pollen). The Reproductive ground-plan hypothesis of Amdam et al. proposes that foraging DOL is regulated by the networks that controlled foraging behavior during the reproductive life cycle of honey bee ancestors. Here we test a proposed mechanism through which the ovary of the facultatively sterile worker impacts foraging bias. The proposed mechanism suggests that the ovary has a regulatory effect on sucrose sensitivity, and sucrose sensitivity impacts nectar loading. We tested this mechanism by measuring worker ovary size (ovariole number), sucrose sensitivity, and sucrose solution load size collected from a rate-controlled artificial feeder. We found a significant interaction between ovariole number and sucrose sensitivity on sucrose solution load size when using low concentration nectar. This supports our proposed mechanism. As nectar and pollen loading are not independent, a mechanism impacting nectar load size would also impact pollen load size.

  16. Association between gravitational force and tissue metabolism in periparturient rats

    NASA Technical Reports Server (NTRS)

    Zakrzewska, E. I.; Maple, R.; Lintault, L.; Wade, C.; Baer, L.; Ronca, A.; Plaut, K.

    2004-01-01

    Recently, interest in mammalian reproduction and offspring survival in altered gravity has been growing. Because successful lactation is critical for mammalian neonate survival, we have been studying the effect of gravity metabolism. We have shown an exponential relationship between glucose metabolic rate in mammary tissue of periparturient rats and an increase in gravity load. In this study we showed that changes in mammary metabolic rate due to gravity force were accompanied by a decrease in glucose metabolism in adipose tissue and by a reduced size of adipocytes. We assume that these changes are likely due to changes in prolactin or leptin levels related to altered gravity load.

  17. Reduced mechanical load decreases the density, stiffness, and strength of cancellous bone of the mandibular condyle.

    PubMed

    Giesen, E B W; Ding, M; Dalstra, M; van Eijden, T M G J

    2003-05-01

    To investigate the influence of decreased mechanical loading on the density and mechanical properties of the cancellous bone of the human mandibular condyle. Destructive compressive mechanical tests were performed on cancellous bone specimens.Background. Reduced masticatory function in edentate people leads to a reduction of forces acting on the mandible. As bone reacts to its mechanical environment a change in its material properties can be expected. Cylindrical bone specimens were obtained from dentate and edentate embalmed cadavers. Mechanical parameters were determined in the axial and in the transverse directions. Subsequently, density parameters were determined according to a method based on Archimedes' principle. The apparent density and volume fraction of the bone were about 18% lower in the edentate group; no age-related effect on density was found. The decrease of bone in the edentate group was associated with a lower stiffness and strength (about 22% and 28%, respectively). The ultimate strain, however, did not differ between the two groups. Both groups had similar mechanical anisotropy; in axial loading the bone was stiffer and stronger than in transverse loading. Reduced mechanical load had affected the density and herewith the mechanical properties of condylar cancellous bone, but not its anisotropy. The change in material properties of the cancellous bone after loss of teeth indicate that the mandibular condyle is sensitive for changes in its mechanical environment. Therefore, changes in mechanical loading of the condyle have to be accounted for in surgical procedures of the mandible.

  18. Mechano-Chemical Interactions at Cement-Geomaterial Interfaces in Repository and Borehole Scenarios

    NASA Astrophysics Data System (ADS)

    Mohagheghi, J. R.; Dewers, T. A.; Matteo, E. N.; Heath, J. E.; Jove Colon, C. F.; Fuller, T.

    2017-12-01

    A number of factors negatively affect wellbore integrity including interactions at boundaries between cement and surrounding geomaterial. These include mechanical and chemical mechanisms that can lead to wellbore failure. To examine these interactions, potential coupling, and pathways to failure, we discuss progress on an experimental and modeling study involving cement-clay and cement-salt interfaces. A sample shotcrete-bentonite interface from the FEBEX heater test at the Grimsel Test Site in Switzerland is examined using multi-beam scanning electron microscopy (mSEM) at 4 nm resolution over an area 10's of square millimeters. We examine changes in alteration as manifested by pore structural changes as a function of distance from the interface. A parallel effort examines time-dependent changes in interface structure in cement cores in a triaxial coreholder. Cores are exposed to conditions of 70oC, 14 MPa pressure, and small differential loads, with degradation being monitored by effluent pH, pulse-echo ultrasonics, and piston displacement (measuring sample shortening). We will measure the mechanical consequences of interface alteration using nano-indentation. Experimental results are being incorporated as a validation effort in a coupled reactive-transport mechanics model linking the Sandia ALBANY finite element code, the KAYENTA elasto-plastic constitutive model, with the reactive transport code PFLOTRAN. Plans call to apply the model to understanding the evolution of the FEBEX sample, as well as a cement-salt sample from the Waste Isolation Pilot Plant in Carlsbad, New Mexico. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc. for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-NA0003525. SAND 2017-8277 A

  19. Mechanical properties of cancellous bone in the human mandibular condyle are anisotropic.

    PubMed

    Giesen, E B; Ding, M; Dalstra, M; van Eijden, T M

    2001-06-01

    The objective of the present study was (1) to test the hypothesis that the elastic and failure properties of the cancellous bone of the mandibular condyle depend on the loading direction, and (2) to relate these properties to bone density parameters. Uniaxial compression tests were performed on cylindrical specimens (n=47) obtained from the condyles of 24 embalmed cadavers. Two loading directions were examined, i.e., a direction coinciding with the predominant orientation of the plate-like trabeculae (axial loading) and a direction perpendicular to the plate-like trabeculae (transverse loading). Archimedes' principle was applied to determine bone density parameters. The cancellous bone was in axial loading 3.4 times stiffer and 2.8 times stronger upon failure than in transverse loading. High coefficients of correlation were found among the various mechanical properties and between them and the apparent density and volume fraction. The anisotropic mechanical properties can possibly be considered as a mechanical adaptation to the loading of the condyle in vivo.

  20. Role of STIM1 (Stromal Interaction Molecule 1) in Hypertrophy-Related Contractile Dysfunction.

    PubMed

    Troupes, Constantine D; Wallner, Markus; Borghetti, Giulia; Zhang, Chen; Mohsin, Sadia; von Lewinski, Dirk; Berretta, Remus M; Kubo, Hajime; Chen, Xiongwen; Soboloff, Jonathan; Houser, Steven

    2017-07-07

    Pathological increases in cardiac afterload result in myocyte hypertrophy with changes in myocyte electrical and mechanical phenotype. Remodeling of contractile and signaling Ca 2+ occurs in pathological hypertrophy and is central to myocyte remodeling. STIM1 (stromal interaction molecule 1) regulates Ca 2+ signaling in many cell types by sensing low endoplasmic reticular Ca 2+ levels and then coupling to plasma membrane Orai channels to induce a Ca 2+ influx pathway. Previous reports suggest that STIM1 may play a role in cardiac hypertrophy, but its role in electrical and mechanical phenotypic alterations is not well understood. To define the contributions of STIM1-mediated Ca 2+ influx on electrical and mechanical properties of normal and diseased myocytes, and to determine whether Orai channels are obligatory partners for STIM1 in these processes using a clinically relevant large animal model of hypertrophy. Cardiac hypertrophy was induced by slow progressive pressure overload in adult cats. Hypertrophied myocytes had increased STIM1 expression and activity, which correlated with altered Ca 2 + -handling and action potential (AP) prolongation. Exposure of hypertrophied myocytes to the Orai channel blocker BTP2 caused a reduction of AP duration and reduced diastolic Ca 2+ spark rate. BTP2 had no effect on normal myocytes. Forced expression of STIM1 in cultured adult feline ventricular myocytes increased diastolic spark rate and prolonged AP duration. STIM1 expression produced an increase in the amount of Ca 2+ stored within the sarcoplasmic reticulum and activated Ca 2+ /calmodulin-dependent protein kinase II. STIM1 expression also increased spark rates and induced spontaneous APs. STIM1 effects were eliminated by either BTP2 or by coexpression of a dominant negative Orai construct. STIM1 can associate with Orai in cardiac myocytes to produce a Ca 2+ influx pathway that can prolong the AP duration and load the sarcoplasmic reticulum and likely contributes to the altered electromechanical properties of the hypertrophied heart. © 2017 American Heart Association, Inc.

  1. Load application for the contact mechanics analysis and wear prediction of total knee replacement.

    PubMed

    Zhang, Jing; Chen, Zhenxian; Wang, Ling; Li, Dichen; Jin, Zhongmin

    2017-05-01

    Tibiofemoral contact forces in total knee replacement have been measured at the medial and lateral sites respectively using an instrumented prosthesis, and predicted from musculoskeletal multibody dynamics models with a reasonable accuracy. However, it is uncommon that the medial and lateral forces are applied separately to replace a total axial load according to the ISO standard in the majority of current finite element analyses. In this study, we quantified the different effects of applying the medial and lateral loads separately versus the traditional total axial load application on contact mechanics and wear prediction of a patient-specific knee prosthesis. The load application position played an important role under the medial-lateral load application. The loading set which produced the closest load distribution to the multibody dynamics model was used to predict the contact mechanics and wear for the prosthesis and compared with the total axial load application. The medial-lateral load distribution using the present method was found to be closer to the multibody dynamics prediction than the traditional total axial load application, and the maximum contact pressure and contact area were consistent with the corresponding load variation. The predicted total volumetric wear rate and area were similar between the two load applications. However, the split of the predicted wear volumes on the medial and the lateral sides was different. The lateral volumetric wear rate was 31.46% smaller than the medial from the traditional load application prediction, while from the medial-lateral load application, the lateral side was only 11.8% smaller than the medial. The medial-lateral load application could provide a new and more accurate method of load application for patient-specific preclinical contact mechanics and wear prediction of knee implants.

  2. Dynamic Response and Failure Mechanism of Brittle Rocks Under Combined Compression-Shear Loading Experiments

    NASA Astrophysics Data System (ADS)

    Xu, Yuan; Dai, Feng

    2018-03-01

    A novel method is developed for characterizing the mechanical response and failure mechanism of brittle rocks under dynamic compression-shear loading: an inclined cylinder specimen using a modified split Hopkinson pressure bar (SHPB) system. With the specimen axis inclining to the loading direction of SHPB, a shear component can be introduced into the specimen. Both static and dynamic experiments are conducted on sandstone specimens. Given carefully pulse shaping, the dynamic equilibrium of the inclined specimens can be satisfied, and thus the quasi-static data reduction is employed. The normal and shear stress-strain relationships of specimens are subsequently established. The progressive failure process of the specimen illustrated via high-speed photographs manifests a mixed failure mode accommodating both the shear-dominated failure and the localized tensile damage. The elastic and shear moduli exhibit certain loading-path dependence under quasi-static loading but loading-path insensitivity under high loading rates. Loading rate dependence is evidently demonstrated through the failure characteristics involving fragmentation, compression and shear strength and failure surfaces based on Drucker-Prager criterion. Our proposed method is convenient and reliable to study the dynamic response and failure mechanism of rocks under combined compression-shear loading.

  3. Prescribed fire experiences on crop residue removal for biomass exploitations. Application to the maritime pine forests in the Mediterranean Basin.

    PubMed

    Molina, Juan Ramón; García, Juan Pedro; Fernández, Juan José; Rodríguez Y Silva, Francisco

    2018-01-15

    Socioeconomic changes, climate change, rural migration and fire exclusion have led to a high woody biomass accumulation increasing potential wildfire severity. Mechanical thinning and prescribed burning practices are commonly used to prevent large fires. The purpose of this study was to assess burning treatment effectiveness following mechanical thinning from biomass harvesting. Prescribed burning to reduce residue removal could help mitigate fire behavior, mainly in strategic management or critical focal points. Field samplings were conducted before and immediately after burnings on different environmental scenarios where fuel load was classified by categories. Prescribed fires reduced available fuel in all fuel categories, mainly in surface litter layer. Total fuel load reduction ranged from 59.07% to 86.18%. In this sense, fuel reduction effects were more pronounced when burns were conducted fewer than 10% on surface litter moisture. The difference in fuel consumption among scenarios was higher for most all woody fuel components and decomposition litter layer than for surface litter layer. Managers can use this information to design technical prescription to achieve the targets while decomposed litter retention maintaining the soil properties and biodiversity. Understanding the most effective "burn window" should help better plan prescribed burning, both in term of fire behavior and fuel consumption, without altering ecosystem properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Reuse of de-inking sludge from wastepaper recycling in cement mortar products.

    PubMed

    Yan, Shiqin; Sagoe-Crentsil, Kwesi; Shapiro, Gretta

    2011-08-01

    This paper presents results of an investigation into the use of de-inking sludge from a paper recycling mill as feedstock material in the manufacture of cement mortar products, including masonry blocks and mortar renders. Both physical and mechanical properties of mortar specimens containing various amounts of de-inking sludge were investigated. It was observed that the addition of de-inking sludge to cement mortar at a fixed water-to-cement ratio significantly reduced flow properties and increased setting time. Water absorption and volume of permeable voids of cement mortar increased with increased dosage of de-inking sludge, with a corresponding reduction of bulk density. The 91-day compressive strength of mortar samples with 2.5 wt% and 20 wt% de-inking sludge loadings retained 83% and 62% respectively of the reference mortar strength. The corresponding drying shrinkage increased by up to 160% compared to reference samples. However, a de-inking sludge loading of up to 2.5 wt% did not significantly alter measured physical and mechanical properties. The results demonstrate that despite the high moisture absorbance of de-inking sludge due to its organic matter and residual cellulose fibre content, it serves as a potential supplementary additive and its cellulosic content proving to be an active set retardant to cementitious masonry products. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Geochemical and lithological factors in acid precipitation

    Treesearch

    James R. Kramer

    1976-01-01

    Acid precipitation is altered by interaction with rocks, sediment and soil. A calcareous region buffers even the most intense loading at pH ~8; an alumino silicate region with unconsolidated sediment buffers acid loadings at pH ~6.5; alumino silicate outcrops are generally acidified. Either FeOOH or alumino silicates are probable H+...

  6. Estimating Summer Nutrient Concentrations in Northeastern Lakes from SPARROW Load Predictions and Modeled Lake Depth and Volume

    EPA Science Inventory

    Global nutrient cycles have been altered by use of fossil fuels and fertilizers resulting in increases in nutrient loads to aquatic systems. In the United States, excess nutrients have been repeatedly reported as the primary cause of lake water quality impairments. Setting nutr...

  7. Alterations in cholesterol metabolism-related genes in sporadic Alzheimer's disease.

    PubMed

    Picard, Cynthia; Julien, Cédric; Frappier, Josée; Miron, Justin; Théroux, Louise; Dea, Doris; Breitner, John C S; Poirier, Judes

    2018-06-01

    Genome-wide association studies have identified several cholesterol metabolism-related genes as top risk factors for late-onset Alzheimer's disease (LOAD). We hypothesized that specific genetic variants could act as disease-modifying factors by altering the expression of those genes. Targeted association studies were conducted with available genomic, transcriptomic, proteomic, and histopathological data from 3 independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Quebec Founder Population (QFP), and the United Kingdom Brain Expression Consortium (UKBEC). First, a total of 273 polymorphisms located in 17 cholesterol metabolism-related loci were screened for associations with cerebrospinal fluid LOAD biomarkers beta amyloid, phosphorylated tau, and tau (from the ADNI) and with amyloid plaque and tangle densities (from the QFP). Top polymorphisms were then contrasted with gene expression levels measured in 134 autopsied healthy brains (from the UKBEC). In the end, only SREBF2 polymorphism rs2269657 showed significant dual associations with LOAD pathological biomarkers and gene expression levels. Furthermore, SREBF2 expression levels measured in LOAD frontal cortices inversely correlated with age at death; suggesting a possible influence on survival rate. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Noncontact minimally invasive technique for the assessment of mechanical properties of single cardiac myocyte via magnetic field loading

    NASA Astrophysics Data System (ADS)

    Yin, Shizhuo; Zhang, Xueqian; Cheung, Joseph; Wu, Juntao; Zhan, Chun; Xue, Jinchao

    2004-07-01

    In this paper, a unique non-contact, minimum invasive technique for the assessment of mechanical properties of single cardiac myocyte is presented. The assessment process includes following major steps: (1) attach a micro magnetic bead to the cell to be measured, (2) measure the contractile performance of the cell under the different magnetic field loading, (3) calculate mechanical loading force, and (4) derive the contractile force from the measured contraction data under different magnetic field loading.

  9. Cyclic strain alters the expression and release of angiogenic factors by human tendon cells.

    PubMed

    Mousavizadeh, Rouhollah; Khosravi, Shahram; Behzad, Hayedeh; McCormack, Robert G; Duronio, Vincent; Scott, Alex

    2014-01-01

    Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

  10. Cyclic Strain Alters the Expression and Release of Angiogenic Factors by Human Tendon Cells

    PubMed Central

    Mousavizadeh, Rouhollah; Khosravi, Shahram; Behzad, Hayedeh; McCormack, Robert G.; Duronio, Vincent; Scott, Alex

    2014-01-01

    Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy. PMID:24824595

  11. Optical and probe determination of soot concentrations in a model gas turbine combustor

    NASA Technical Reports Server (NTRS)

    Eckerle, W. A.; Rosfjord, T. J.

    1986-01-01

    An experimental program was conducted to track the variation in soot loading in a generic gas turbine combustor. The burner is a 12.7-cm dia cylindrical device consisting of six sheet-metal louvers. Determination of soot loading along the burner length is achieved by measurement at the exit of the combustor and then at upstream stations by sequential removal of liner louvers to shorten burner length. Alteration of the flow field approaching and within the shortened burners is minimized by bypassing flow in order to maintain a constant linear pressure drop. The burner exhaust flow is sampled at the burner centerline to determine soot mass concentration and smoke number. Characteristic particle size and number density, transmissivity of the exhaust flow, and local radiation from luminous soot particles in the exhaust are determined by optical techniques. Four test fuels are burned at three fuel-air ratios to determine fuel chemical property and flow temperature influences. Particulate concentration data indicate a strong oxidation mechanism in the combustor secondary zone, though the oxidation is significantly affected by flow temperature. Soot production is directly related to fuel smoke point.

  12. Electrical signal transmission and gap junction regulation in a bone cell network: a cable model for an osteon

    NASA Technical Reports Server (NTRS)

    Zhang, D.; Cowin, S. C.; Weinbaum, S.

    1997-01-01

    A cable model is formulated to estimate the spatial distribution of intracellular electric potential and current, from the cement line to the lumen of an osteon, as the frequency of the loading and the conductance of the gap junction are altered. The model predicts that the characteristic diffusion time for the spread of current along the membrane of the osteocytic processes, 0.03 sec, is nearly the same as the predicted pore pressure relaxation time in Zeng et al. (Annals of Biomedical Engineering. 1994) for the draining of the bone fluid into the osteonal canal. This approximate equality of characteristic times causes the cable to behave as a high-pass, low-pass filter cascade with a maximum in the spectral response for the intracellular potential at approximately 30 Hz. This behavior could be related to the experiments of Rubin and McLeod (Osteoporosis, Academic Press, 1996) which show that live bone appears to be selectively responsive to mechanical loading in a specific frequency range (15-30 Hz) for several species.

  13. A Soft Gripper with Rigidity Tunable Elastomer Strips as Ligaments.

    PubMed

    Nasab, Amir Mohammadi; Sabzehzar, Amin; Tatari, Milad; Majidi, Carmel; Shan, Wanliang

    2017-12-01

    Like their natural counterparts, soft bioinspired robots capable of actively tuning their mechanical rigidity can rapidly transition between a broad range of motor tasks-from lifting heavy loads to dexterous manipulation of delicate objects. Reversible rigidity tuning also enables soft robot actuators to reroute their internal loading and alter their mode of deformation in response to intrinsic activation. In this study, we demonstrate this principle with a three-fingered pneumatic gripper that contains "programmable" ligaments that change stiffness when activated with electrical current. The ligaments are composed of a conductive, thermoplastic elastomer composite that reversibly softens under resistive heating. Depending on which ligaments are activated, the gripper will bend inward to pick up an object, bend laterally to twist it, and bend outward to release it. All of the gripper motions are generated with a single pneumatic source of pressure. An activation-deactivation cycle can be completed within 15 s. The ability to incorporate electrically programmable ligaments in a pneumatic or hydraulic actuator has the potential to enhance versatility and reduce dependency on tubing and valves.

  14. Wear Behavior and Mechanism of a Cr-Mo-V Cast Hot-Working Die Steel

    NASA Astrophysics Data System (ADS)

    Wei, M. X.; Wang, S. Q.; Zhao, Y. T.; Chen, K. M.; Cui, X. H.

    2011-06-01

    The wear behavior and mechanisms of a Cr-Mo-V cast hot-working die steel with three microstructures (tempered martensite, troostite, and sorbite) were studied systematically through the dry-sliding wear tests within a normal load range of 50 to 300 N and an ambient temperature range of 298 K to 673 K (25 °C to 400 °C) by a pin-on-disk high-temperature wear machine. Five different mechanisms were observed in the experiments, namely adhesive, abrasive, mild oxidative, oxidative, and extrusive wear; one or more of those mechanisms would be dominant within particular ranges of load and temperature. The transition of wear mechanisms depended on the formation of tribo-oxides, which was related closely to load and temperature, and their delamination, which was mainly influenced by the matrix. By increasing the load and ambient temperature, the protective effect of tribo-oxides first strengthened, then decreased, and in some cases disappeared. Under a load ranging 50 to 300 N at 298 K (25 °C) and a load of 50 N at 473 K (200 °C), adhesive wear was the dominant wear mechanism, and abrasive wear appeared simultaneously. The wear was of mild oxidative type under a load ranging 100 to 300 N at 473 K (200 °C) and a load ranging 50 to 150 N at 673 K (400 °C) for tempered martensite and tempered troostite as well as under a load of 100 N at 473 K (200 °C) and a load ranging 50 to 100 N at 673 K (400 °C) for tempered sorbite. At the load of 200 N or greater, or the temperatures above 673 K (400 °C), oxidative wear (beyond mild oxidative wear) prevailed. When the highest load of 300 N at 673 K (400 °C) was applied, extrusive wear started to dominate for the tempered sorbite.

  15. Alterations in muscle mass and contractile phenotype in response to unloading models: role of transcriptional/pretranslational mechanisms

    PubMed Central

    Baldwin, Kenneth M.; Haddad, Fadia; Pandorf, Clay E.; Roy, Roland R.; Edgerton, V. Reggie

    2013-01-01

    Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a motor unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC) gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s). Hence, this review will examine findings from three different animal models of unloading: (1) space flight (SF), i.e., microgravity; (2) hindlimb suspension (HS), a procedure that chronically eliminates weight bearing of the lower limbs; and (3) spinal cord isolation (SI), a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: (1) all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; (2) transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and (3) signaling pathways impacting these alterations appear to be similar in each of the models investigated. PMID:24130531

  16. Tendon exhibits complex poroelastic behavior at the nanoscale as revealed by high-frequency AFM-based rheology.

    PubMed

    Connizzo, Brianne K; Grodzinsky, Alan J

    2017-03-21

    Tendons transmit load from muscle to bone by utilizing their unique static and viscoelastic tensile properties. These properties are highly dependent on the composition and structure of the tissue matrix, including the collagen I hierarchy, proteoglycans, and water. While the role of matrix constituents in the tensile response has been studied, their role in compression, particularly in matrix pressurization via regulation of fluid flow, is not well understood. Injured or diseased tendons and tendon regions that naturally experience compression are known to have alterations in glycosaminoglycan content, which could modulate fluid flow and ultimately mechanical function. While recent theoretical studies have predicted tendon mechanics using poroelastic theory, no experimental data have directly demonstrated such behavior. In this study, we use high-bandwidth AFM-based rheology to determine the dynamic response of tendons to compressive loading at the nanoscale and to determine the presence of poroelastic behavior. Tendons are found to have significant characteristic dynamic relaxation behavior occurring at both low and high frequencies. Classic poroelastic behavior is observed, although we hypothesize that the full dynamic response is caused by a combination of flow-dependent poroelasticity as well as flow-independent viscoelasticity. Tendons also demonstrate regional dependence in their dynamic response, particularly near the junction of tendon and bone, suggesting that the structural and compositional heterogeneity in tendon may be responsible for regional poroelastic behavior. Overall, these experiments provide the foundation for understanding fluid-flow-dependent poroelastic mechanics of tendon, and the methodology is valuable for assessing changes in tendon matrix compressive behavior at the nanoscale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Analysis and comparison of the biomechanical properties of univalved and bivalved cast models.

    PubMed

    Crickard, Colin V; Riccio, Anthony I; Carney, Joseph R; Anderson, Terrence D

    2011-01-01

    Fiberglass casts are frequently valved to relieve the pressure associated with upper extremity swelling after a surgical procedure or when applied after reduction of a displaced fracture in a child. Although different opinions exist regarding the valving of casts, no research to date has explored the biomechanical effects of this commonly used technique. As cast integrity is essential for the maintenance of fracture reduction, it is important to understand whether casts are structurally compromised after valving. Understanding the effects of valving on cast integrity may help guide clinicians in the technique of valving while minimizing the potential for a loss of fracture reduction. Thirty standardized cylindrical fiberglass cast models were created. Ten models were left intact, 10 were univalved, and 10 were bivalved. All the models were mechanically tested by a 3-point bending apparatus secured to a biaxial materials testing system. Load to failure and bending stiffness were recorded for each sample. Differences in load of failure and bending stiffness were compared among the groups. Unvalved cast models had the highest failure load and bending stiffness, whereas bivalved casts showed the lowest value for both failure load and bending stiffness. Univalved casts had a failure load measured to be between those of unvalved and bivalved cast models. Analysis of variance showed significance when failure load and bending stiffness data among all the groups were compared. A post hoc Bonferroni statistical analysis showed significance in bending stiffness between intact and bivalved models (P < 0.01), intact and univalved models (P < 0.01), but no significant difference in bending stiffness between univalved and bivalved models (P > 0.01). Differences in measured failure load values were found to be statistically significant among all cast models (P < 0.01). Valving significantly decreases the bending stiffness and load to failure of fiberglass casts. Univalved casts have a higher load to failure than bivalved casts. Valving adversely alters the structural integrity of fiberglass casts. This may impair a cast's ability to effectively immobilize an extremity or maintain a fracture reduction.

  18. The role of adipocytokines in the pathogenesis of knee joint osteoarthritis.

    PubMed

    Richter, Magdalena; Trzeciak, Tomasz; Owecki, Maciej; Pucher, Andrzej; Kaczmarczyk, Jacek

    2015-06-01

    Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.

  19. Physiology of respiratory disturbances in muscular dystrophies

    PubMed Central

    Lo Mauro, Antonella

    2016-01-01

    Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. Key points A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination. In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia. Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness. Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase. The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. Educational aims To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy. To understand the impact of respiratory disturbances in patients with muscular dystrophy. To provide a brief description of the main forms of muscular dystrophy with their respiratory implications. PMID:28210319

  20. Physiology of respiratory disturbances in muscular dystrophies.

    PubMed

    Lo Mauro, Antonella; Aliverti, Andrea

    2016-12-01

    Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e . when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination.In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia.Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness.Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase.The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy.To understand the impact of respiratory disturbances in patients with muscular dystrophy.To provide a brief description of the main forms of muscular dystrophy with their respiratory implications.

  1. Kinematic and kinetic comparison of running in standard and minimalist shoes.

    PubMed

    Willy, Richard W; Davis, Irene S

    2014-02-01

    The purpose of this study was to determine whether running in a minimalist shoe results in a reduction in ground reaction forces and alters kinematics over standard shoe running. The secondary purpose of this study was to determine whether within-session accommodation to a novel minimalist shoe occurs. Subjects were 14 male, rearfoot striking runners who had never run in a minimalist shoe. Subjects were tested while running 3.35 m·s(-1) for 10 min on an instrumented treadmill in a minimalist and a standard shoe as three-dimensional lower extremity kinematics and kinetics were evaluated. Data were collected at minute 1 and then again after 10 min of running in both shoe conditions to evaluate accommodation to the shoe conditions. Shoe-time interactions were not found for any of the variables of interest. Minimalist shoe running resulted in no changes in step length (P = 0.967) or in step rate (P = 0.230). At footstrike, greater knee flexion (P = 0.001) and greater dorsiflexion angle (P = 0.025) were noted in the minimalist shoe. Vertical impact peak (P = 0.017) and average vertical loading rate (P < 0.000) were greater during minimalist shoe running. There were main effects of time as dorsiflexion angle decreased (P = 0.035), foot inclination at footstrike decreased (P = 0.048), and knee flexion at footstrike increased (P = 0.002), yet the vertical impact peak (P = 0.002) and average vertical loading rate (P < 0.000) increased. Running in a minimalist shoe appears to, at least in the short term, increase loading of the lower extremity over standard shoe running. The accommodation period resulted in less favorable landing mechanics in both shoes. These findings bring into question whether minimal shoes will provide enough feedback to induce an alteration that is similar to barefoot running.

  2. Meso-Scale Finite Element Analysis of Mechanical Behavior of 3D Braided Composites Subjected to Biaxial Tension Loadings

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Curiel-Sosa, Jose L.; Bui, Tinh Quoc

    2018-04-01

    In many engineering applications, 3D braided composites are designed for primary loading-bearing structures, and they are frequently subjected to multi-axial loading conditions during service. In this paper, a unit-cell based finite element model is developed for assessment of mechanical behavior of 3D braided composites under different biaxial tension loadings. To predict the damage initiation and evolution of braiding yarns and matrix in the unit-cell, we thus propose an anisotropic damage model based on Murakami damage theory in conjunction with Hashin failure criteria and maximum stress criteria. To attain exact stress ratio, force loading mode of periodic boundary conditions which never been attempted before is first executed to the unit-cell model to apply the biaxial tension loadings. The biaxial mechanical behaviors, such as the stress distribution, tensile modulus and tensile strength are analyzed and discussed. The damage development of 3D braided composites under typical biaxial tension loadings is simulated and the damage mechanisms are revealed in the simulation process. The present study generally provides a new reference to the meso-scale finite element analysis (FEA) of multi-axial mechanical behavior of other textile composites.

  3. Running speed increases plantar load more than per cent body weight on an AlterG® treadmill.

    PubMed

    Thomson, Athol; Einarsson, Einar; Witvrouw, Erik; Whiteley, Rod

    2017-02-01

    AlterG® treadmills allow for running at different speeds as well as at reduced bodyweight (BW), and are used during rehabilitation to reduce the impact load. The aim of this study was to quantify plantar loads borne by the athlete during rehabilitation. Twenty trained male participants ran on the AlterG® treadmill in 36 conditions: all combinations of indicated BW (50-100%) paired with different walking and running speeds (range 6-16 km · hr -1 ) in a random order. In-shoe maximum plantar force (Fmax) was recorded using the Pedar-X system. Fmax was lowest at the 6 km · hr -1 at 50% indicated BW condition at 1.02 ± 0.21BW and peaked at 2.31 ± 0.22BW for the 16 km · hr -1 at 100% BW condition. Greater increases in Fmax were seen when increasing running speed while holding per cent BW constant than the reverse (0.74BW-0.91BW increase compared to 0.19-0.31BW). A table is presented with each of the 36 combinations of BW and running speed to allow a more objective progression of plantar loading during rehabilitation. Increasing running speed rather than increasing indicated per cent BW was shown to have the strongest effect on the magnitude of Fmax across the ranges of speeds and indicated per cent BWs examined.

  4. Do Integrins Mediate the Skeletal Response to Altered Loading?

    NASA Technical Reports Server (NTRS)

    vanderMeulen, Marjolein C. H.

    2004-01-01

    In vivo experiments were performed to examine the role of B1 integrin in skeletal adaptation to reduced and increased loading. Transgenic mice were generated with a dominant negative form of the B1 integrin cytoplasmic domain with expression driven by the osteocalcin promoter (pOCb1DN). This fragment consists of the transmembrane and intracellular domains and interferes with endogenous integrin signalling in vitro. This promoter targets expression of the transgene to mature bone cells. Expression of the transgene was confirmed by immunoprecipitation and western blotting. Reduced loading was generated by hindlimb suspension and increased loading the resumption of normal loading following hindlimb suspension. Two groups of female 35-day old mice were examined: poCb1DN transgenic mice (TG) and wild-type littermate controls (WT). Animals were hindlimb suspended for 1 week (HU, n = l0/gp) or 4 weeks (HU, n = 4 - 7/gp) or suspended for 4 weeks followed by reloading by normal ambulation for 4 weeks (RL, n = l0/gp). Age-matched controls (CT) were pairfed based on the HU food intake. The protocols were approved by the NASA Ames Research Center IACUC. Upon completion of the experimental protocol, body mass was recorded and tissues of interest removed and analyzed following standard procedures. Femoral whole bone structural behavior was measured in torsion to failure to obtain whole bone strength (failure torque) and torsional rigidity. Ash content (ash) and fraction (% ash) were determined for the tibia. Total ash is indicative of bone size whereas %ash is a material property. Tibial curvature was measured from microradiographs. For each experiment, the effects of genotype (TG, WT) and treatment (CT, HU/RL) were assessed by two-factor ANOVA followed by the Tukey-Kramer posthoc to identify significant differences at an alpha level of 0.05. Our goal was to understand differences resulting from altered integrin function in the adaptation to altered loading.

  5. Effects of three different preservation methods on the mechanical properties of human and bovine cortical bone.

    PubMed

    Unger, Stefan; Stefan, Unger; Blauth, Michael; Michael, Blauth; Schmoelz, Werner; Werner, Schmoelz

    2010-12-01

    In the development of new strategies for fracture fixation, new methods have to be tested biomechanically under in vitro conditions before clinical trials can be performed. The gold standard for laboratory evaluations is fresh-frozen specimen. As the availability of fresh-frozen specimens is limited and since their use bears infectious risks, specimens treated with various chemical embalming fluids are also used. These preservation methods may alter the mechanical properties of the specimens used. Therefore, the aims of the present study were to determine the effects of three different preservation methods (formalin fixation (FO), Thiel-fixation (TH), and alcohol-glycerine fixation (AG)) on the elastic and postyield mechanical properties of cortical bone and to compare these properties to those of fresh-frozen (FF) specimens. Cylindrical cortical specimens (diameter 3mm, length 60 mm) were obtained from human femurs (n=48) and bovine tibiae (n=40). Before specimen immersion in different fixation fluids, bone mineral density (BMD) as well as the initial Young's modulus was determined. The Young's modulus was determined in a nondestructive bending test, and measurements were repeated after 6 months of immersion in fixative solution. Subsequent to the nondestructive test, a destructive 3-point bending test was conducted to assess the postyield and fracture properties. The BMD as well as the initial Young's modulus showed no significant differences between the four test groups. After 6 months in fixative solution, the Young's modulus was significantly lowered in human Thiel specimens and only showed minor changes in formalin- and alcohol-glycerine-treated specimens. The plastic energy absorption of human and bovine specimens was altered significantly. Formalin as well as alcohol-glycerine fixation yielded a significant decrease in plastic energy absorption, whereas Thiel fixation significantly increased the plastic energy absorption. Because of the significantly altered plastic mechanical properties of cortical bone, the use fresh-frozen bone specimens is recommended in biomechanical studies investigating failure loads of orthopaedic implants. The use of embalmed specimens should be restricted to pilot tests. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Pathophysiology of hypertension: interactions between macro and microvascular alterations through endothelial dysfunction.

    PubMed

    Yannoutsos, Alexandra; Levy, Bernard I; Safar, Michel E; Slama, Gerard; Blacher, Jacques

    2014-02-01

    Hypertension is a multifactorial systemic chronic disorder through functional and structural macrovascular and microvascular alterations. Macrovascular alterations are featured by arterial stiffening, disturbed wave reflection and altered central to peripheral pulse pressure amplification. Microvascular alterations, including altered wall-to-lumen ratio of larger arterioles, vasomotor tone abnormalities and network rarefaction, lead to disturbed tissue perfusion and susceptibility to ischemia. Central arterial stiffness and microvascular alterations are common denominators of organ damages. Vascular alterations are intercorrelated, amplifying the haemodynamic load and causing further damage in the arterial network. A plausible precursor role of vascular alterations in incident hypertension provides new insights for preventive and therapeutic strategies targeting macro and microvasculature. Cumulative metabolic burden and oxidative stress lead to chronic endothelial injury, promoting structural and functional vascular alterations, especially in the microvascular network. Pathophysiology of hypertension may then be revisited, based on both macrovascular and microvascular alterations, with a precursor role of endothelial dysfunction for the latter.

  7. Influence of altered gait patterns on the hip joint contact forces.

    PubMed

    Carriero, Alessandra; Zavatsky, Amy; Stebbins, Julie; Theologis, Tim; Lenaerts, Gerlinde; Jonkers, Ilse; Shefelbine, Sandra J

    2014-01-01

    Children who exhibit gait deviations often present a range of bone deformities, particularly at the proximal femur. Altered gait may affect bone growth and lead to deformities by exerting abnormal stresses on the developing bones. The objective of this study was to calculate variations in the hip joint contact forces with different gait patterns. Muscle and hip joint contact forces of four children with different walking characteristics were calculated using an inverse dynamic analysis and a static optimisation algorithm. Kinematic and kinetic analyses were based on a generic musculoskeletal model scaled down to accommodate the dimensions of each child. Results showed that for all the children with altered gaits both the orientation and magnitude of the hip joint contact force deviated from normal. The child with the most severe gait deviations had hip joint contact forces 30% greater than normal, most likely due to the increase in muscle forces required to sustain his crouched stance. Determining how altered gait affects joint loading may help in planning treatment strategies to preserve correct loading on the bone from a young age.

  8. Altering the swelling pressures within in vitro engineered cartilage is predicted to modulate the configuration of the collagen network and hence improve tissue mechanical properties.

    PubMed

    Nagel, Thomas; Kelly, Daniel J

    2013-06-01

    Prestress in the collagen network has a significant impact on the material properties of cartilaginous tissues. It is closely related to the recruitment configuration of the collagen network which defines the transition from lax collagen fibres to uncrimped, load-bearing collagen fibres. This recruitment configuration can change in response to alterations in the external environmental conditions. In this study, the influence of changes in external salt concentration or sequential proteoglycan digestion on the configuration of the collagen network of tissue engineered cartilage is investigated using a previously developed computational model. Collagen synthesis and network assembly are assumed to occur in the tissue configuration present during in vitro culture. The model assumes that if this configuration is more compact due to changes in tissue swelling, the collagen network will adapt by lowering its recruitment stretch. When returned to normal physiological conditions, these tissues will then have a higher prestress in the collagen network. Based on these assumptions, the model demonstrates that proteoglycan digestion at discrete time points during culture as well as culture in a hypertonic medium can improve the functionality of tissue engineered cartilage, while culture in hypotonic solution is detrimental to the apparent mechanical properties of the graft. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Divergent Mechanisms Leading to Signaling Dysfunction in Embryonic Muscle by Bisphenol A and Tetrabromobisphenol A

    PubMed Central

    Pessah, Isaac N.

    2017-01-01

    Bisphenol A (BPA) and its brominated derivative tetrabromobisphenol A (TBBPA) are high production volume chemicals used in the manufacture of various consumer products. Although regarded as endocrine disruptors, these chemicals are suspected to exert nongenomic actions on muscle function that are not well understood. Using skeletal muscle microsomes, we examined the effects of BPA and TBBPA on ryanodine receptor type 1 (RyR1), dihydropyridine receptor (DHPR), and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA). We assessed the impact of these chemicals on Ca2+ dynamics and signaling in embryonic skeletal myotubes through fluorescent Ca2+ imaging and measurement of resting membrane potential (Vm). TBBPA activated RyR1 and inhibited DHPR and SERCA, inducing a net efflux of Ca2+ from loaded microsomes, whereas BPA exhibited little or no activity at these targets. Regardless, both compounds disrupted the function of intact myotubes. TBBPA diminished and eventually abrogated Ca2+ transients, altered intracellular Ca2+ equilibrium, and caused Vm depolarization. For some cells, BPA caused rapid Ca2+ transient loss without marked changes in cytosolic and sarcoplasmic reticulum Ca2+ levels, likely owing to altered cellular excitability as a result of BPA-induced Vm hyperpolarization. BPA and TBBPA both interfere with skeletal muscle function through divergent mechanisms that impair excitation-contraction coupling and may be exemplary of their adverse outcomes in other muscle types. PMID:28143888

  10. Hierarchical damage mechanisms in composite materials subjected to fatigue loadings

    NASA Astrophysics Data System (ADS)

    D'Amore, Alberto; Grassia, Luigi

    2018-02-01

    The strength degradation of fiber reinforced composites subjected to constant amplitude (CA) fatigue loadings can be described by a two-parameter residual strength model. From the analytical approach it results that under moderate loadings the multiple damage mechanisms develop with different kinetics and manifest their effectiveness at different time scales highlighting the three-Stage hierarchical nature of damage accumulation in composites. The model captures the sequence of damage accumulation mechanisms from diffuse matrix cracking (I), to fiber/matrix interface failure (II) to fiber and ply rupture and delamination (III). Further, by increasing the loading severity it appears that the different mechanisms superpose witnessing their simultaneous co-existence.

  11. Influence of crop load on the expression patterns of starch metabolism genes in alternate-bearing citrus trees.

    PubMed

    Nebauer, Sergio G; Renau-Morata, Begoña; Lluch, Yolanda; Baroja-Fernández, Edurne; Pozueta-Romero, Javier; Molina, Rosa-Victoria

    2014-07-01

    The fruit is the main sink organ in Citrus and captures almost all available photoassimilates during its development. Consequently, carbohydrate partitioning and starch content depend on the crop load of Citrus trees. Nevertheless, little is known about the mechanisms controlling the starch metabolism at the tree level in relation to presence of fruit. The aim of this study was to find the relation between the seasonal variation of expression and activity of the genes involved in carbon metabolism and the partition and allocation of carbohydrates in 'Salustiana' sweet orange trees with different crop loads. Metabolisable carbohydrates, and the expression and activity of the enzymes involved in sucrose and starch metabolism, including sucrose transport, were determined during the year in the roots and leaves of 40-year-old trees bearing heavy crop loads ('on' trees) and trees with almost no fruits ('off' trees). Fruit altered photoassimilate partitioning in trees. Sucrose content tended to be constant in roots and leaves, and surplus fixed carbon is channeled to starch production. Differences between 'on' and 'off' trees in starch content can be explained by differences in ADP-glucose pyrophosphorylase (AGPP) expression/activity and α-amylase activity which varies depending on crop load. The observed relation of AGPP and UGPP (UDP-glucose pyrophosphorylase) is noteworthy and indicates a direct link between sucrose and starch synthesis. Furthermore, different roles for sucrose transporter SUT1 and SUT2 have been proposed. Variation in soluble sugars content cannot explain the differences in gene expression between the 'on' and 'off' trees. A still unknown signal from fruit should be responsible for this control. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Parasite Load Induces Progressive Spleen Architecture Breakage and Impairs Cytokine mRNA Expression in Leishmania infantum-Naturally Infected Dogs

    PubMed Central

    Cavalcanti, Amanda S.; Ribeiro-Alves, Marcelo; Pereira, Luiza de O. R.; Mestre, Gustavo Leandro; Ferreira, Anna Beatriz Robottom; Morgado, Fernanda N.; Boité, Mariana C.; Cupolillo, Elisa; Moraes, Milton O.; Porrozzi, Renato

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L. infantum in zoonotic VL. Infected dogs develop progressive disease with a large clinical spectrum. A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome. This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil. Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations. By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42). When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups. Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism. All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response. Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ. TNF showed the best negative correlation (r2 = 0.231; p<0.001). Herein we describe impairment on mRNA cytokine expression in leishmania infected dogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture. We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome. PMID:25875101

  13. Self locking coupling mechanism for engaging and moving a load

    DOEpatents

    Wood, Richard L.; Casamajor, Alan B.; Parsons, Richard E.

    1982-01-01

    Coupling mechanism (11) for engaging and lifting a load (12) has a housing (19) with a guide passage (18) for receiving a knob (13) which is secured to the load (12) through a neck (15) of smaller diameter. A hollow ball (23) in the housing (19) has an opening (27) which receives the knob (13) and the ball (23) is then turned to displace the opening (27) from the housing passage (18) and to cause the neck (15) to enter a slot (29) in the ball (23) thereby securing the load (12) to the coupling mechanism (11) as elements (49) of the housing (19) block travel of the neck (15) back into the opening (27) when the ball (23) is turned to the load holding orientation. As engagement of the load (12) and locking of the coupling mechanism are accomplished simultaneously by the same ball (23) motion, operation is simplified and reliability is greatly increased. The ball (23) is preferably turned by a motor (32) through worm gearing (36) and the coupling mechanism (11) may be controlled from a remote location. Among other uses, the coupling mechanism (11) is adaptable to the handling of spent nuclear reactor fuel elements (12).

  14. Prevention by zinc of cadmium-induced alterations in pancreatic and hepatic functions.

    PubMed Central

    Merali, Z; Singhal, R L

    1976-01-01

    Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content. 2 Exposure to cadmium increases hepatic cyclic adenosine 3',5'-monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline- as well as glucagon-stimulated form(s) of adenylate cyclase. 3 In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load. 4 Zinc, when administered at the same time as cadmium, prevents the cadmium-induced lesions in both hepatic and pancreatic functions. 5 The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc. PMID:183849

  15. Regulation of ROCK Activity in Cancer

    PubMed Central

    Morgan-Fisher, Marie; Wewer, Ulla M.

    2013-01-01

    Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

  16. Integrating MRI-based geometry, composition and fiber architecture in a finite element model of the human intervertebral disc.

    PubMed

    Stadelmann, Marc A; Maquer, Ghislain; Voumard, Benjamin; Grant, Aaron; Hackney, David B; Vermathen, Peter; Alkalay, Ron N; Zysset, Philippe K

    2018-05-17

    Intervertebral disc degeneration is a common disease that is often related to impaired mechanical function, herniations and chronic back pain. The degenerative process induces alterations of the disc's shape, composition and structure that can be visualized in vivo using magnetic resonance imaging (MRI). Numerical tools such as finite element analysis (FEA) have the potential to relate MRI-based information to the altered mechanical behavior of the disc. However, in terms of geometry, composition and fiber architecture, current FE models rely on observations made on healthy discs and might therefore not be well suited to study the degeneration process. To address the issue, we propose a new, more realistic FE methodology based on diffusion tensor imaging (DTI). For this study, a human disc joint was imaged in a high-field MR scanner with proton-density weighted (PD) and DTI sequences. The PD image was segmented and an anatomy-specific mesh was generated. Assuming accordance between local principal diffusion direction and local mean collagen fiber alignment, corresponding fiber angles were assigned to each element. Those element-wise fiber directions and PD intensities allowed the homogenized model to smoothly account for composition and fibrous structure of the disc. The disc's in vitro mechanical behavior was quantified under tension, compression, flexion, extension, lateral bending and rotation. The six resulting load-displacement curves could be replicated by the FE model, which supports our approach as a first proof of concept towards patient-specific disc modeling. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Sudden cardiac death: the pro-arrhythmic interaction of an acute loading with an underlying substrate.

    PubMed

    Sutherland, George R

    2017-10-21

    Sudden cardiac death (SCD) is a complex phenomenon, occurring either in apparently normal individuals or in those where there is a recognized underlying cardiac abnormality. In both groups, the lethal arrhythmia has frequently been related to the physiologic trigger of either exercise or stress. Prior research into SCD has focused mainly on a combination of identifying either vulnerable myocardial substrates; pharmacological approaches to altering electrical activation/repolarisation in substrates; or the suppression of induced lethal arrhythmias with implantable defibrillators. However, it has been suggested that in a significant number of cases, the interaction of a transient induced trigger with a pre-existing electrical or mechanical substrate is the basis for the induction of the sustained lethal arrhythmia. In this manuscript we will discuss the precise mechanisms whereby one of such potential physiologic trigger: an acute change in systolic blood pressure, can induce a sequence of alterations in global and local cardiac mechanics which in turn result in regional left ventricular post-systolic deformation which, mediated (through stretch-induced changes in local mechano-electrical coupling) provokes local electrical after-depolarisations which can spill over into complex runs of premature ventricular beats. These local acute pressure/stretch induced runs of ventricular ectopy originate in either basal or apical normal myocardium and, in combination with a co-existing distal pro-arrhymic substrate, can interact to induce a lethal arrhythmia. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.

  18. Stress as a common risk factor for obesity and addiction

    PubMed Central

    2013-01-01

    Stress is associated with obesity and the neurobiology of stress overlaps significantly with that of appetite and energy regulation. This review will discuss stress, allostasis, the neurobiology of stress and its overlap with neural regulation of appetite and energy homeostasis. Stress is a key risk factor in the development of addiction and in addiction relapse. High levels of stress changes eating patterns and augments consumption of highly palatable (HP) foods, which in turn, increases incentive salience of HP foods and allostatic load. The neurobiological mechanisms by which stress affects reward pathways to potentiate motivation and consumption of HP foods as well as addictive drugs is discussed. With enhanced incentive salience of HP foods and over-consumption of these foods, there are adaptations in stress and reward circuits that promote stress-related and HP food-related motivation as well as concomitant metabolic adaptations, including alterations in glucose metabolism, insulin sensitivity, and other hormones related to energy homeostatsis. These metabolic changes in turn may also affect dopaminergic activity to influence food motivation and intake of HP foods. An integrative heuristic model is proposed wherein repeated high levels of stress alter the biology of stress and appetite/energy regulation, with both components directly affecting neural mechanisms contributing to stress-induced and food cue-induced HP food motivation and engagement in overeating of such foods to enhance risk of weight gain and obesity. Future directions in research are identified to increase understanding of the mechanisms by which stress may increase risk of weight gain and obesity. PMID:23541000

  19. Stress as a common risk factor for obesity and addiction.

    PubMed

    Sinha, Rajita; Jastreboff, Ania M

    2013-05-01

    Stress is associated with obesity, and the neurobiology of stress overlaps significantly with that of appetite and energy regulation. This review will discuss stress, allostasis, the neurobiology of stress and its overlap with neural regulation of appetite, and energy homeostasis. Stress is a key risk factor in the development of addiction and in addiction relapse. High levels of stress changes eating patterns and augments consumption of highly palatable (HP) foods, which in turn increases incentive salience of HP foods and allostatic load. The neurobiological mechanisms by which stress affects reward pathways to potentiate motivation and consumption of HP foods as well as addictive drugs is discussed. With enhanced incentive salience of HP foods and overconsumption of these foods, there are adaptations in stress and reward circuits that promote stress-related and HP food-related motivation as well as concomitant metabolic adaptations, including alterations in glucose metabolism, insulin sensitivity, and other hormones related to energy homeostasis. These metabolic changes in turn might also affect dopaminergic activity to influence food motivation and intake of HP foods. An integrative heuristic model is proposed, wherein repeated high levels of stress alter the biology of stress and appetite/energy regulation, with both components directly affecting neural mechanisms contributing to stress-induced and food cue-induced HP food motivation and engagement in overeating of such foods to enhance risk of weight gain and obesity. Future directions in research are identified to increase understanding of the mechanisms by which stress might increase risk of weight gain and obesity. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. Potential regenerative rehabilitation technology: implications of mechanical stimuli to tissue health

    PubMed Central

    2014-01-01

    Background Mechanical loads induced through muscle contraction, vibration, or compressive forces are thought to modulate tissue plasticity. With the emergence of regenerative medicine, there is a need to understand the optimal mechanical environment (vibration, load, or muscle force) that promotes cellular health. To our knowledge no mechanical system has been proposed to deliver these isolated mechanical stimuli in human tissue. We present the design, performance, and utilization of a new technology that may be used to study localized mechanical stimuli on human tissues. A servo-controlled vibration and limb loading system were developed and integrated into a single instrument to deliver vibration, compression, or muscle contractile loads to a single limb (tibia) in humans. The accuracy, repeatability, transmissibility, and safety of the mechanical delivery system were evaluated on eight individuals with spinal cord injury (SCI). Findings The limb loading system was linear, repeatable, and accurate to less than 5, 1, and 1 percent of full scale, respectively, and transmissibility was excellent. The between session tests on individuals with spinal cord injury (SCI) showed high intra-class correlations (>0.9). Conclusions All tests supported that therapeutic loads can be delivered to a lower limb (tibia) in a safe, accurate, and measureable manner. Future collaborations between engineers and cellular physiologists will be important as research programs strive to determine the optimal mechanical environment for developing cells and tissues in humans. PMID:24894666

  1. Thermodynamics and mechanics of photochemcially reacting polymers

    NASA Astrophysics Data System (ADS)

    Long, Rong; Qi, H. Jerry; Dunn, Martin L.

    2013-11-01

    We develop a thermodynamics and mechanics theory for polymers that when irradiated with light, undergo photochemical reactions that alter their macromolecular structure, e.g., by bond breaking and/or reformation, and in turn affect their mechanical and physical behavior. This emerging class of highly-engineered active materials shows great promise for myriad applications and is a subset of a broader class of polymers with covalent bonds that can be dynamically tuned with various environmental stimuli. We formulate a general thermodynamic and kinetic framework to model the complex photochemical-thermal-mechanical coupling in these materials. Our theory considers the behavior of a polymer that is subjected to the combination of mechanical and thermal loading while simultaneously irradiated by light with multiple frequency components and directions. We introduce an approach to model the photochemical reactions that can change the network topology, resulting chemical species transport, heat conduction and finite deformation. We describe the interaction of the material with light via a radiometric description and show how it can be linked to a full electromagnetic treatment when appropriate and if desired. Our approach is sufficiently general to permit the modeling of various materials that operate via different photochemical reaction mechanisms. After formulating the general theory, we specialize it to a polymer that when irradiated with light undergoes a series of photochemical reactions that cause chain scission and reformation which continuously rearrange the polymer network into a stress-free configuration. Based on the operant physical mechanisms we develop a constitutive model using a polymer chain decomposition and evolution approach to track the molecular structure changes during simultaneous irradiation and mechanical loading. In the special case of isothermal conditions with monochromatic and unidirectional irradiation, we recover a previous model based on intuitive ad-hoc assumptions and thus put it on strong thermodynamic footing. Finally we use our model to simulate the behavior of a polymer that is biaxially stretched and then irradiated with light from one side. We simulate the process and emphasize the spontaneous bending that occurs due to inhomogeneous photoinduced stress relaxation. From our theory, we obtain an analytical expression of a characteristic time for photo-induced stress relaxation in terms of the dominating system parameters.

  2. Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

    PubMed Central

    Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W.

    2017-01-01

    The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions. PMID:28775711

  3. Lower-limb veins are thicker and vascular reactivity is decreased in a rat PCOS model: concomitant vitamin D3 treatment partially prevents these changes.

    PubMed

    Várbíró, Szabolcs; Sára, Levente; Antal, Péter; Monori-Kiss, Anna; Tőkés, Anna-Mária; Monos, Emil; Benkő, Rita; Csibi, Noémi; Szekeres, Maria; Tarszabo, Robert; Novak, Agnes; Paragi, Péter; Nádasy, György L

    2014-09-15

    Polycystic ovary syndrome (PCOS) causes vascular damage to arteries; however, there are no data for its effect on veins. Our aim was to clarify the effects of dihydrotestosterone (DHT)-induced PCOS both on venous biomechanics and on pharmacological reactivity in a rat model and to test the possible modulatory role of vitamin D3 (vitD). PCOS was induced in female Wistar rats by DHT treatment (83 μg/day, subcutaneous pellet). After 10 wk, the venous biomechanics, norepinephrine (NE)-induced contractility, and acetylcholine-induced relaxation were tested in saphenous veins from control animals and from animals treated with DHT or DHT with vitD using pressure angiography. Additionally, the expression levels of endothelial nitric oxide synthase (eNOS) and cyclooxygenase (COX-2) were measured using immunohistochemistry. Increased diameter, wall thickness, and distensibility as well as decreased vasoconstriction were detected after the DHT treatment. Concomitant vitD treatment lowered the mechanical load on the veins, reduced distensibility, and resulted in vessels that were more relaxed. Although there was no difference in the endothelial dilation tested using acetylcholine (ACh), the blocking effect of N(G)-nitro-l-arginine methyl ester (l-NAME) was lower and was accompanied by lower COX-2 expression in the endothelium after the DHT treatment. Supplementation with vitD prevented these alterations. eNOS expression did not differ among the three groups. We conclude that the hyperandrogenic state resulted in thicker vein walls. These veins showed early remodeling and altered vasorelaxant mechanisms similar to those of varicose veins. Alterations caused by the chronic DHT treatment were prevented partially by concomitant vitD administration. Copyright © 2014 the American Physiological Society.

  4. A constitutive model for the mechanical characterization of the plantar fascia.

    PubMed

    Natali, Arturo N; Pavan, Piero G; Stecco, Carla

    2010-10-01

    A constitutive model is proposed to describe the mechanical behavior of the plantar fascia. The mechanical characterization of the plantar fascia regards the role in the foot biomechanics and it is involved in many alterations of its functional behavior, both of mechanical and nonmechanical origin. The structural conformation of the plantar fascia in its middle part is characterized by the presence of collagen fibers reinforcing the tissue along a preferential orientation, which is that supporting the major loading. According to this anatomical evidence, the tissue is described by developing an isotropic fiber-reinforced constitutive model and since the elastic response of the fascia is here considered, the constitutive model is based on the theory of hyperelasticity. The model is consistent with a kinematical description of large strains mechanical behavior, which is typical of soft tissues. A fitting procedure of the constitutive model is implemented making use of experimental curves taken from the literature and referring to specimens of human plantar fascia. A satisfactory fitting of the tensile behavior of the plantar fascia has been performed, showing that the model correctly interprets the mechanical behavior of the tissue in the light of comparison to experimental data at disposal. A critical analysis of the model with respect to the problem of the identification of the constitutive parameters is proposed as the basis for planning a future experimental investigation of mechanical behavior of the plantar fascia.

  5. Influence of multi-cycle loading on the structure and mechanics of marine mussel plaques.

    PubMed

    Wilhelm, Menaka H; Filippidi, Emmanouela; Waite, J Herbert; Valentine, Megan T

    2017-10-18

    The proteinaceous byssal plaque-thread structures created by marine mussels exhibit extraordinary load-bearing capability. Although the nanoscopic protein interactions that support interfacial adhesion are increasingly understood, major mechanistic questions about how mussel plaques maintain toughness on supramolecular scales remain unanswered. This study explores the mechanical properties of whole mussel plaques subjected to repetitive loading cycles, with varied recovery times. Mechanical measurements were complemented with scanning electron microscopy to investigate strain-induced structural changes after yield. Multicyclic loading of plaques decreases their low-strain stiffness and introduces irreversible, strain-dependent plastic damage within the plaque microstructure. However, strain history does not compromise critical strength or maximum extension compared with plaques monotonically loaded to failure. These results suggest that a multiplicity of force transfer mechanisms between the thread and plaque-substrate interface allow the plaque-thread structure to accommodate a wide range of extensions as it continues to bear load. This improved understanding of the mussel system at micron-to-millimeter lengthscales offers strategies for including similar fail-safe mechanisms in the design of soft, tough and resilient synthetic structures.

  6. Ovarian Control of Nectar Collection in the Honey Bee (Apis mellifera)

    PubMed Central

    Siegel, Adam J.; Freedman, Colin; Page, Robert E.

    2012-01-01

    Honey bees are a model system for the study of division of labor. Worker bees demonstrate a foraging division of labor (DOL) by biasing collection towards carbohydrates (nectar) or protein (pollen). The Reproductive ground-plan hypothesis of Amdam et al. proposes that foraging DOL is regulated by the networks that controlled foraging behavior during the reproductive life cycle of honey bee ancestors. Here we test a proposed mechanism through which the ovary of the facultatively sterile worker impacts foraging bias. The proposed mechanism suggests that the ovary has a regulatory effect on sucrose sensitivity, and sucrose sensitivity impacts nectar loading. We tested this mechanism by measuring worker ovary size (ovariole number), sucrose sensitivity, and sucrose solution load size collected from a rate-controlled artificial feeder. We found a significant interaction between ovariole number and sucrose sensitivity on sucrose solution load size when using low concentration nectar. This supports our proposed mechanism. As nectar and pollen loading are not independent, a mechanism impacting nectar load size would also impact pollen load size. PMID:22558073

  7. Real-Time Assessment of Mechanical Tissue Trauma in Surgery.

    PubMed

    Chandler, James H; Mushtaq, Faisal; Moxley-Wyles, Benjamin; West, Nicholas P; Taylor, Gregory W; Culmer, Peter R

    2017-10-01

    This work presents a method to assess and prevent tissue trauma in real-time during surgery. Tissue trauma occurs routinely during laparoscopic surgery with potentially severe consequences. As such, it is crucial that a surgeon is able to regulate the pressure exerted by surgical instruments. We propose a novel method to assess the onset of tissue trauma by considering the mechanical response of tissue as it is loaded in real-time. We conducted a parametric study using a lab-based grasping model and differing load conditions. Mechanical stress-time data were analyzed to characterize the tissue response to grasps. Qualitative and quantitative histological analyses were performed to inspect damage characteristics of the tissue under different load conditions. These were correlated against the mechanical measures to identify the nature of trauma onset with respect to our predictive metric. Results showed increasing tissue trauma with load and a strong correlation with the mechanical response of the tissue. Load rate and load history also showed a clear effect on tissue response. The proposed method for trauma assessment was effective in identifying damage. The metric can be normalized with respect to loading rate and history, making it feasible in the unconstrained environment of intraoperative surgery. This work demonstrates that tissue trauma can be predicted using mechanical measures in real-time. Applying this technique to laparoscopic tools has the potential to reduce unnecessary tissue trauma and its associated complications by indicating through user feedback or actively regulating the mechanical impact of surgical instruments.

  8. In vitro mechanical stimulation facilitates stress dissipation and sealing ability at the conventional glass ionomer cement-dentin interface.

    PubMed

    Toledano, Manuel; Osorio, Raquel; Osorio, Estrella; Cabello, Inmaculada; Toledano-Osorio, Manuel; Aguilera, Fátima S

    2018-06-01

    The aim of this study was to evaluate the induced changes in the chemical and mechanical performance at the glass-ionomer cement-dentin interface after mechanical load application. A conventional glass-ionomer cement (GIC) (Ketac Bond), and a resin-modified glass-ionomer cement (RMGIC) (Vitrebond Plus) were used. Bonded interfaces were stored in simulated body fluid, and then tested or submitted to the mechanical loading challenge. Different loading waveforms were applied: No cycling, 24 h cycled in sine or loaded in sustained hold waveforms. The cement-dentin interface was evaluated using a nano-dynamic mechanical analysis, estimating the complex modulus and tan δ. Atomic Force Microscopy (AFM) imaging, Raman analysis and dye assisted confocal microscopy evaluation (CLSM) were also performed. The complex modulus was lower and tan delta was higher at interfaces promoted with the GIC if compared to the RMGIC unloaded. The conventional GIC attained evident reduction of nanoleakage. Mechanical loading favored remineralization and promoted higher complex modulus and lower tan delta values at interfaces with RMGIC, where porosity, micropermeability and nanoleakage were more abundant. Mechanical stimuli diminished the resistance to deformation and increased the stored energy at the GIC-dentin interface. The conventional GIC induced less porosity and nanoleakage than RMGIC. The RMGIC increased nanoleakage at the porous interface, and dye sorption appeared within the cement. Both cements created amorphous and crystalline apatites at the interface depending on the type of mechanical loading. Remineralization, lower stress concentration and resistance to deformation after mechanical loading improved the sealing of the GIC-dentin interface. In vitro oral function will favor high levels of accumulated energy and permits micropermeability at the RMGIC-dentin interface which will become remineralized. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. A novel ex vivo model of compressive immature rib fractures at pathophysiological rates of loading.

    PubMed

    Beadle, Nicola; Burnett, Timothy L; Hoyland, Judith A; Sherratt, Michael J; Freemont, Anthony J

    2015-11-01

    Compressive rib fractures are considered to be indicative of non-accidental injury (NAI) in infants, which is a significant and growing issue worldwide. The diagnosis of NAI is often disputed in a legal setting, and as a consequence there is a need to model such injuries ex vivo in order to characterise the forces required to produce non-accidental rib fractures. However, current models are limited by type of sample, loading method and rate of loading. Here, we aimed to: i) develop a loading system for inducing compressive fractures in whole immature ribs that is more representative of the physiological conditions and mechanism of injury employed in NAI and ii) assess the influence of loading rate and rib geometry on the mechanical performance of the tissue. Porcine ribs (5-6 weeks of age) from 12 animals (n=8 ribs/animal) were subjected to axial compressive load directed through the anterior-posterior rib axis at loading rates of 1, 30, 60 or 90 mm/s. Key mechanical parameters (including peak load, load and percentage deformation to failure and effective stiffness) were quantified from the load-displacement curves. Measurements of the rib length, thickness at midpoint, distance between anterior and posterior extremities, rib curvature and fracture location were determined from radiographs. This loading method typically produced incomplete fractures around the midpoint of the ribs, with 87% failing in this manner; higher loads and less deformation were required for ribs to completely fracture through both cortices. Loading rate, within the range of 1-90 mm/s, did not significantly affect any key mechanical parameters of the ribs. Load-displacement curves displaying characteristic and quantifiable features were produced for 90% of the ribs tested, and multiple regression analyses indicate that, in addition to the geometrical variables, there are other factors such as the micro- and nano-structure that influence the measured mechanical data. A reproducible method of inducing fractures in a consistent location in immature porcine ribs has been successfully developed. Fracture appearance may be indicative of the amount of load and deformation that produced the fracture, which is an important finding for NAI, where knowledge of the aetiology of fractures is vital. Characteristic rib behaviour independent of loading rate and, to an extent, rib geometry has been demonstrated, allowing further investigation into how the complex micro- and nano-structure of immature ribs influences the mechanical performance under compressive load. This research will ultimately enable improved characterisation of the loading pattern involved in non-accidental rib fractures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Characterization of Solid Polymers, Ceramic Gap Filler, and Closed-Cell Polymer Foam Using Low-Load Test Methods

    NASA Technical Reports Server (NTRS)

    Herring, Helen M.

    2008-01-01

    Various solid polymers, polymer-based composites, and closed-cell polymer foam are being characterized to determine their mechanical properties, using low-load test methods. The residual mechanical properties of these materials after environmental exposure or extreme usage conditions determines their value in aerospace structural applications. In this experimental study, four separate polymers were evaluated to measure their individual mechanical responses after thermal aging and moisture exposure by dynamic mechanical analysis. A ceramic gap filler, used in the gaps between the tiles on the Space Shuttle, was also tested, using dynamic mechanical analysis to determine material property limits during flight. Closed-cell polymer foam, used for the Space Shuttle External Tank insulation, was tested under low load levels to evaluate how the foam's mechanical properties are affected by various loading and unloading scenarios.

  11. Changes in tendon spatial frequency parameters with loading.

    PubMed

    Pearson, Stephen J; Engel, Aaron J; Bashford, Gregory R

    2017-05-24

    To examine and compare the loading related changes in micro-morphology of the patellar tendon. Fifteen healthy young males (age 19±3yrs, body mass 83±5kg) were utilised in a within subjects matched pairs design. B mode ultrasound images were taken in the sagittal plane of the patellar tendon at rest with the knee at 90° flexion. Repeat images were taken whilst the subjects were carrying out maximal voluntary isometric contractions. Spatial frequency parameters related to the tendon morphology were determined within regions of interest (ROI) from the B mode images at rest and during isometric contractions. A number of spatial parameters were observed to be significantly different between resting and contracted images (Peak spatial frequency radius (PSFR), axis ratio, spatial Q-factor, PSFR amplitude ratio, and the sum). These spatial frequency parameters were indicative of acute alterations in the tendon micro-morphology with loading. Acute loading modifies the micro-morphology of the tendon, as observed via spatial frequency analysis. Further research is warranted to explore its utility with regard to different loading induced micro-morphological alterations, as these could give valuable insight not only to aid strengthening of this tissue but also optimization of recovery from injury and treatment of conditions such as tendinopathies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Influence of LVAD function on mechanical unloading and electromechanical delay: a simulation study.

    PubMed

    Heikhmakhtiar, Aulia Khamas; Ryu, Ah Jin; Shim, Eun Bo; Song, Kwang-Soup; Trayanova, Natalia A; Lim, Ki Moo

    2018-05-01

    This study hypothesized that a left ventricular assist device (LVAD) shortens the electromechanical delay (EMD) by mechanical unloading. The goal of this study is to examine, by computational modeling, the influence of LVAD on EMD for four heart failure (HF) cases ranging from mild HF to severe HF. We constructed an integrated model of an LVAD-implanted cardiovascular system, then we altered the Ca 2+ transient magnitude, with scaling factors 1, 0.9, 0.8, and 0.7 representing HF1, HF2, HF3, and HF4, respectively, in order of increasing HF severity. The four HF conditions are classified into two groups. Group one is the four HF conditions without LVAD, and group two is the conditions treated with continuous LVAD pump. The single-cell mechanical responses showed that EMD was prolonged with the higher load. The findings indicated that in group one, the HF-induced Ca2 + transient remodeling prolonged the mechanical activation time (MAT) and decreased the contractile tension, which reduced the left ventricle (LV) pressure, and increased the end-diastolic strain. In group two, LVAD shortened MAT of the ventricles. Furthermore, LVAD reduced the contractile tension, and end-diastolic strain, but increased the aortic pressure. The computational study demonstrated that LVAD shortens EMD by mechanical unloading of the ventricle.

  13. MEMS-based Force-clamp Analysis of the Role of Body Stiffness in C. elegans Touch Sensation

    PubMed Central

    Petzold, Bryan C.; Park, Sung-Jin; Mazzochette, Eileen A.; Goodman, Miriam B.; Pruitt, Beth L.

    2013-01-01

    Touch is enabled by mechanoreceptor neurons in the skin and plays an essential role in our everyday lives, but is among the least understood of our five basic senses. Force applied to the skin deforms these neurons and activates ion channels within them. Despite the importance of the mechanics of the skin in determining mechanoreceptor neuron deformation and ultimately touch sensation, the role of mechanics in touch sensitivity is poorly understood. Here, we use the model organism Caenorhabditis elegans to directly test the hypothesis that body mechanics modulate touch sensitivity. We demonstrate a microelectromechanical system (MEMS)-based force clamp that can apply calibrated forces to freely crawling C. elegans worms and measure touch-evoked avoidance responses. This approach reveals that wild-type animals sense forces < 1 μN and indentation depths < 1 μm. We use both genetic manipulation of the skin and optogenetic modulation of body wall muscles to alter body mechanics. We find that small changes in body stiffness dramatically affect force sensitivity, while having only modest effects on indentation sensitivity. We investigate the theoretical body deformation predicted under applied force and conclude that local mechanical loads induce inward bending deformation of the skin to drive touch sensation in C. elegans. PMID:23598612

  14. Electrophysiological experiments in microgravity: lessons learned and future challenges.

    PubMed

    Wuest, Simon L; Gantenbein, Benjamin; Ille, Fabian; Egli, Marcel

    2018-01-01

    Advances in electrophysiological experiments have led to the discovery of mechanosensitive ion channels (MSCs) and the identification of the physiological function of specific MSCs. They are believed to play important roles in mechanosensitive pathways by allowing for cells to sense their mechanical environment. However, the physiological function of many MSCs has not been conclusively identified. Therefore, experiments have been developed that expose cells to various mechanical loads, such as shear flow, membrane indentation, osmotic challenges and hydrostatic pressure. In line with these experiments, mechanical unloading, as experienced in microgravity, represents an interesting alternative condition, since exposure to microgravity leads to a series of physiological adaption processes. As outlined in this review, electrophysiological experiments performed in microgravity have shown an influence of gravity on biological functions depending on ion channels at all hierarchical levels, from the cellular level to organs. In this context, calcium signaling represents an interesting cellular pathway, as it involves the direct action of calcium-permeable ion channels, and specific gravitatic cells have linked graviperception to this pathway. Multiple key proteins in the graviperception pathways have been identified. However, measurements on vertebrae cells have revealed controversial results. In conclusion, electrophysiological experiments in microgravity have shown that ion-channel-dependent physiological processes are altered in mechanically unloaded conditions. Future experiments may provide a better understanding of the underlying mechanisms.

  15. Effects of mechanical repetitive load on bone quality around implants in rat maxillae

    PubMed Central

    Uto, Yusuke; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

    2017-01-01

    Greater understanding and acceptance of the new concept “bone quality”, which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones. PMID:29244883

  16. Effects of mechanical repetitive load on bone quality around implants in rat maxillae.

    PubMed

    Uto, Yusuke; Kuroshima, Shinichiro; Nakano, Takayoshi; Ishimoto, Takuya; Inaba, Nao; Uchida, Yusuke; Sawase, Takashi

    2017-01-01

    Greater understanding and acceptance of the new concept "bone quality", which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of mechanical loads on Sema3A production and bone quality based on bone cells and collagen fibers around implants in rat maxillae. Grade IV-titanium threaded implants were placed at 4 weeks post-extraction in maxillary first molars. Implants received mechanical loads (10 N, 3 Hz for 1800 cycles, 2 days/week) for 5 weeks from 3 weeks post-implant placement to minimize the effects of wound healing processes by implant placement. Bone structures, bone mineral density (BMD), Sema3A production and bone quality based on bone cells and collagen fibers were analyzed using microcomputed tomography, histomorphometry, immunohistomorphometry, polarized light microscopy and birefringence measurement system inside of the first and second thread (designated as thread A and B, respectively), as mechanical stresses are concentrated and differently distributed on the first two threads from the implant neck. Mechanical load significantly increased BMD, but not bone volume around implants. Inside thread B, but not thread A, mechanical load significantly accelerated Sema3A production with increased number of osteoblasts and osteocytes, and enhanced production of both type I and III collagen. Moreover, mechanical load also significantly induced preferential alignment of collagen fibers in the lower flank of thread B. These data demonstrate that mechanical load has different effects on Sema3A production and bone quality based on bone cells and collagen fibers between the inside threads of A and B. Mechanical load-induced Sema3A production may be differentially regulated by the type of bone structure or distinct stress distribution, resulting in control of bone quality around implants in jaw bones.

  17. Real-Time Measurement of Solute Transport Within the Lacunar-Canalicular System of Mechanically Loaded Bone: Direct Evidence for Load-Induced Fluid Flow

    PubMed Central

    Price, Christopher; Zhou, Xiaozhou; Li, Wen; Wang, Liyun

    2011-01-01

    Since proposed by Piekarski and Munro in 1977, load-induced fluid flow through the bone lacunar-canalicular system (LCS) has been accepted as critical for bone metabolism, mechanotransduction, and adaptation. However, direct unequivocal observation and quantification of load-induced fluid and solute convection through the LCS have been lacking due to technical difficulties. Using a novel experimental approach based on fluorescence recovery after photobleaching (FRAP) and synchronized mechanical loading and imaging, we successfully quantified the diffusive and convective transport of a small fluorescent tracer (sodium fluorescein, 376 Da) in the bone LCS of adult male C57BL/6J mice. We demonstrated that cyclic end-compression of the mouse tibia with a moderate loading magnitude (–3 N peak load or 400 µɛ surface strain at 0.5 Hz) and a 4-second rest/imaging window inserted between adjacent load cycles significantly enhanced (+31%) the transport of sodium fluorescein through the LCS compared with diffusion alone. Using an anatomically based three-compartment transport model, the peak canalicular fluid velocity in the loaded bone was predicted (60 µm/s), and the resulting peak shear stress at the osteocyte process membrane was estimated (∼5 Pa). This study convincingly demonstrated the presence of load-induced convection in mechanically loaded bone. The combined experimental and mathematical approach presented herein represents an important advance in quantifying the microfluidic environment experienced by osteocytes in situ and provides a foundation for further studying the mechanisms by which mechanical stimulation modulates osteocytic cellular responses, which will inform basic bone biology, clinical understanding of osteoporosis and bone loss, and the rational engineering of their treatments. © 2011 American Society for Bone and Mineral Research. PMID:20715178

  18. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

    PubMed Central

    Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

  19. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

    PubMed

    Govey, Peter M; Zhang, Yue; Donahue, Henry J

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

  20. Statistical model for the mechanical behavior of the tissue engineering non-woven fibrous matrices under large deformation.

    PubMed

    Rizvi, Mohd Suhail; Pal, Anupam

    2014-09-01

    The fibrous matrices are widely used as scaffolds for the regeneration of load-bearing tissues due to their structural and mechanical similarities with the fibrous components of the extracellular matrix. These scaffolds not only provide the appropriate microenvironment for the residing cells but also act as medium for the transmission of the mechanical stimuli, essential for the tissue regeneration, from macroscopic scale of the scaffolds to the microscopic scale of cells. The requirement of the mechanical loading for the tissue regeneration requires the fibrous scaffolds to be able to sustain the complex three-dimensional mechanical loading conditions. In order to gain insight into the mechanical behavior of the fibrous matrices under large amount of elongation as well as shear, a statistical model has been formulated to study the macroscopic mechanical behavior of the electrospun fibrous matrix and the transmission of the mechanical stimuli from scaffolds to the cells via the constituting fibers. The study establishes the load-deformation relationships for the fibrous matrices for different structural parameters. It also quantifies the changes in the fiber arrangement and tension generated in the fibers with the deformation of the matrix. The model reveals that the tension generated in the fibers on matrix deformation is not homogeneous and hence the cells located in different regions of the fibrous scaffold might experience different mechanical stimuli. The mechanical response of fibrous matrices was also found to be dependent on the aspect ratio of the matrix. Therefore, the model establishes a structure-mechanics interdependence of the fibrous matrices under large deformation, which can be utilized in identifying the appropriate structure and external mechanical loading conditions for the regeneration of load-bearing tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Measurements of bed load transport on Pacific Creek, Buffalo Fork and The Snake River in Grand Teton National Park, Wyoming

    USGS Publications Warehouse

    Erwin, Susannah O.; Schmidt, J.C.

    2006-01-01

    Dams disrupt the flow of both of water and sediment through a watershed. Channel morphology is a function of discharge and sediment load, and perturbations caused by dams often alter channel form, causing significant geomorphic and, potentially, ecological changes (e.g. Petts and Gurnell, 2005). At the first order, dams often produce a flow regime that is profoundly altered in the timing, magnitude, and frequency of flows (Magilligan and Nislow, 2005). Yet, the nature of channel adjustments will be specific to both the physical setting, size of the river, dam characteristics, and nature and severity of the flow regulation (Church 1995; Knighton, 1998).

  2. Vineyard floor management and cluster thinning inconsistently affect ‘Pinot noir’ crop load, berry composition, and wine quality

    USDA-ARS?s Scientific Manuscript database

    A 3-year field study was developed to determine relationships between crop load metrics and berry composition for ‘Pinot noir’ in a cool-climate through the manipulation of vegetative growth and fruit yield using competitive cover cropping and cluster thinning, respectively. To alter vine vigor, per...

  3. 76 FR 8782 - Underground Construction Standard; Extension of the Office of Management and Budget's (OMB...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... employers to post warning signs or notices during underground construction; these paragraphs are (b)(3), (i... Standard requires employers to inspect and load test hoists when they install them, and at least annually thereafter; they must also inspect and load test a hoist after making any repairs or alterations to it that...

  4. Altered Frontal and Transverse Plane Tibiofemoral Kinematics and Patellofemoral Malalignments During Downhill Gait in Patients with Mixed Knee Osteoarthritis

    PubMed Central

    Farrokhi, Shawn; Meholic, Brad; Chuang, Wei-Neng; Gustafson, Jonathan A.; Fitzgerald, G. Kelley; Tashman, Scott

    2015-01-01

    Patients with knee osteoarthritis often present with signs of mixed tibiofemoral and patellofemoral joint disease. It has been suggested that altered frontal and transverse plane knee joint mechanics play a key role in compartment-specific patterns of knee osteoarthritis, but invivo evidence in support of this premise remains limited. Using Dynamic Stereo X-ray techniques, the aim of this study was to compare the frontal and transverse plane tibiofemoral kinematics and patellofemoral malalignments during the loading response phase of downhill gait in three groups of older adults: patients with medial tibiofemoral compartment and coexisting patellofemoral osteoarthritis (n=11); patients with lateral tibiofemoral compartment and coexisting patellofemoral osteoarthritis (n=10); and an osteoarthritis-free control group (n=22). Patients with lateral compartment osteoarthritis walked with greater and increasing degrees of tibiofemoral abduction compared to the medial compartment osteoarthritis and the control groups who walked with increasing degrees of tibiofemoral adduction. Additionally, the medial and lateral compartment osteoarthritis groups demonstrated reduced degrees of tibiofemoral internal rotation compared to the control group. Both medial and lateral compartment osteoarthritis groups also walked with increasing degrees of lateral patella tilt and medial patella translation during the loading response phase of downhill gait. Our findings suggest that despite the differences in frontal and transverse plane tibiofemoral kinematics between patients with medial and lateral compartment osteoarthritis, the malalignments of their arthritic patellofemoral joint appears to be similar. Further research is needed to determine if these kinematic variations are relevant targets for interventions to reduce pain and disease progression in patients with mixed disease. PMID:26087880

  5. Use of Body Armor Protection Levels with Squad Automatic Weapon Fighting Load Impacts Soldier Performance, Mobility, and Postural Control

    DTIC Science & Technology

    2015-05-01

    changes have been historically seen with the heavier approach march load between 21 kg and 33 kg (Schiffman et al., 2006, and Harman et al., 1999) or...the heaviest emergency approach march load greater than 32 kg (Attwells et al., 2006, and Harman et al., 1999). Increasing ballistic protection...vital to maintaining upright posture while walking ( Harman et al., 1999). Alterations made lower in the kinematic chain, such as the hip flexion

  6. Anteroventral third ventricle (AV3V) lesions alter c-fos expression induced by salt loading

    NASA Technical Reports Server (NTRS)

    Rocha, M. J.; Beltz, T. G.; Dornelles, R. C.; Johnson, A. K.; Franci, C. R.

    1999-01-01

    Lesion of the anteroventral third-ventricle region (AV3VX) reduced saline consumption. Salt loading in AV3VX rats resulted in reduced but not completely abolished c-fos expression in the supraoptic and paraventricular nuclei. Intrinsic osmosensitivity of the magnocellular neurons, or input from other brain areas, such as the subfornical and median preoptic nuclei, may account for this residual c-fos expression. These regions showed c-fos expression following salt loading. Copyright 1999 Elsevier Science B.V.

  7. The mechanism of bolt loading

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1992-01-01

    It is shown that the mechanism of bolt loading for preloaded fasteners can be effectively portrayed through simple spring models and some algebraic manipulations. Understanding schematically what is involved in such joints provides insight into the distribution of loads. The developed equations confirm that for both symmetric and nonsymmetric joints the loading plane factor and the stiffness factor directly affect the load seen in preloaded fasteners. The manner in which an external loading is transferred through the joint can be explained as energy dissipated in the various springs of both the abutment and the bolt itself.

  8. Remodeling by fibroblasts alters the rate-dependent mechanical properties of collagen.

    PubMed

    Babaei, Behzad; Davarian, Ali; Lee, Sheng-Lin; Pryse, Kenneth M; McConnaughey, William B; Elson, Elliot L; Genin, Guy M

    2016-06-01

    The ways that fibroblasts remodel their environment are central to wound healing, development of musculoskeletal tissues, and progression of pathologies such as fibrosis. However, the changes that fibroblasts make to the material around them and the mechanical consequences of these changes have proven difficult to quantify, especially in realistic, viscoelastic three-dimensional culture environments, leaving a critical need for quantitative data. Here, we observed the mechanisms and quantified the mechanical effects of fibroblast remodeling in engineered tissue constructs (ETCs) comprised of reconstituted rat tail (type I) collagen and human fibroblast cells. To study the effects of remodeling on tissue mechanics, stress-relaxation tests were performed on ETCs cultured for 24, 48, and 72h. ETCs were treated with deoxycholate and tested again to assess the ECM response. Viscoelastic relaxation spectra were obtained using the generalized Maxwell model. Cells exhibited viscoelastic damping at two finite time constants over which the ECM showed little damping, approximately 0.2s and 10-30s. Different finite time constants in the range of 1-7000s were attributed to ECM relaxation. Cells remodeled the ECM to produce a relaxation time constant on the order of 7000s, and to merge relaxation finite time constants in the 0.5-2s range into a single time content in the 1s range. Results shed light on hierarchical deformation mechanisms in tissues, and on pathologies related to collagen relaxation such as diastolic dysfunction. As fibroblasts proliferate within and remodel a tissue, they change the tissue mechanically. Quantifying these changes is critical for understanding wound healing and the development of pathologies such as cardiac fibrosis. Here, we characterize for the first time the spectrum of viscoelastic (rate-dependent) changes arising from the remodeling of reconstituted collagen by fibroblasts. The method also provides estimates of the viscoelastic spectra of fibroblasts within a three-dimensional culture environment. Results are of particular interest because of the ways that fibroblasts alter the mechanical response of collagen at loading frequencies associated with cardiac contraction in humans. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Mechanics of instability-related delimination growth

    NASA Technical Reports Server (NTRS)

    Whitcomb, John D.

    1988-01-01

    Local buckling of a delaminated group of plies can lead to higher interlaminar stresses and delamination growth. The mechanics of instability-related delamination growth (IRDG) had been described previously for the through-width delamination. This paper describes the mechanics of IRDG for the embedded delamination subjected to either uniaxial or axisymmetric loads. The mechanics of IRDG are used to explain the dramatic differences in strain-energy release rates observed for the through-width, the axisymmetrically loaded embedded delamination, and the uniaxially loaded embedded delamination.

  10. Grips for testing of electrical characteristics of a specimen under a mechanical load

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Briggs, Timothy; Loyola, Bryan

    Various technologies to facilitate coupled electrical and mechanical measurement of conductive materials are disclosed herein. A gripping device simultaneously holds a specimen in place and causes contact to be made between the specimen and a plurality of electrodes connected to an electrical measuring device. An electrical characteristic of the specimen is then measured while a mechanical load is applied to the specimen, and a relationship between the mechanical load and changes in the electrical characteristic can be identified.

  11. Straightening of a wavy strip: An elastic-plastic contact problem including snap-through

    NASA Technical Reports Server (NTRS)

    Fischer, D. F.; Rammerstorfer, F. G.

    1980-01-01

    The nonlinear behavior of a wave like deformed metal strip during the levelling process were calculated. Elastic-plastic material behavior as well as nonlinearities due to large deformations were considered. The considered problem lead to a combined stability and contact problem. It is shown that, despite the initially concentrated loading, neglecting the change of loading conditions due to altered contact domains may lead to a significant error in the evaluation of the nonlinear behavior and particularly to an underestimation of the stability limit load. The stability was examined by considering the load deflection path and the behavior of a load-dependent current stiffness parameter in combination with the determinant of the current stiffness matrix.

  12. Bio-functionalization of biomedical metals.

    PubMed

    Xiao, M; Chen, Y M; Biao, M N; Zhang, X D; Yang, B C

    2017-01-01

    Bio-functionalization means to endow biomaterials with bio-functions so as to make the materials or devices more suitable for biomedical applications. Traditionally, because of the excellent mechanical properties, the biomedical metals have been widely used in clinic. However, the utilized functions are basically supporting or fixation especially for the implantable devices. Nowadays, some new functions, including bioactivity, anti-tumor, anti-microbial, and so on, are introduced to biomedical metals. To realize those bio-functions on the metallic biomedical materials, surface modification is the most commonly used method. Surface modification, including physical and chemical methods, is an effective way to alter the surface morphology and composition of biomaterials. It can endow the biomedical metals with new surface properties while still retain the good mechanical properties of the bulk material. Having analyzed the ways of realizing the bio-functionalization, this article briefly summarized the bio-functionalization concepts of six hot spots in this field. They are bioactivity, bony tissue inducing, anti-microbial, anti-tumor, anticoagulation, and drug loading functions. Copyright © 2016. Published by Elsevier B.V.

  13. Respiratory Muscle Plasticity

    PubMed Central

    Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

    2014-01-01

    Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

  14. Damage mechanisms in PBT-GF30 under thermo-mechanical cyclic loading

    NASA Astrophysics Data System (ADS)

    Schaaf, A.; De Monte, M.; Hoffmann, C.; Vormwald, M.; Quaresimin, M.

    2014-05-01

    The scope of this paper is the investigation of damage mechanisms at microscopic scale on a short glass fiber reinforced polybutylene terephthalate (PBT-GF30) under thermo-mechanical cyclic loading. In addition the principal mechanisms are verified through micro mechanical FE models. In order to investigate the fatigue behavior of the material both isothermal strain controlled fatigue (ISCF) tests at three different temperatures and thermo-mechanical fatigue (TMF) tests were conducted on plain and notched specimens, manufactured by injection molding. The goal of the work is to determine the damage mechanisms occurring under TMF conditions and to compare them with the mechanisms occurring under ISCF. For this reason fracture surfaces of TMF and ISCF samples loaded at different temperature levels were analyzed using scanning electron microscopy. Furthermore, specimens that failed under TMF were examined on microsections revealing insight into both crack initiation and crack propagation. The findings of this investigation give valuable information about the main damage mechanisms of PBT-GF30 under TMF loading and serve as basis for the development of a TMF life estimation methodology.

  15. Mechanical loading stimulates ecto-ATPase activity in human tendon cells.

    PubMed

    Tsuzaki, M; Bynum, D; Almekinders, L; Faber, J; Banes, A J

    2005-09-01

    Response to external stimuli such as mechanical signals is critical for normal function of cells, especially when subjected to repetitive motion. Tenocytes receive mechanical stimuli from the load-bearing matrix as tension, compression, and shear stress during tendon gliding. Overloading a tendon by high strain, shear, or repetitive motion can cause matrix damage. Injury may induce cytokine expression, matrix metalloproteinase (MMP) expression and activation resulting in loss of biomechanical properties. These changes may result in tendinosis or tendinopathy. Alternatively, an immediate effector molecule may exist that acts in a signal-dampening pathway. Adenosine 5'-triphosphate (ATP) is a candidate signal blocker of mechanical stimuli. ATP suppresses load-inducible inflammatory genes in human tendon cells in vitro. ATP and other extracellular nucleotide signaling are regulated efficiently by two distinct mechanisms: purinoceptors via specific receptor-ligand binding and ecto-nucleotidases via the hydrolysis of specific nucleotide substrates. ATP is released from tendon cells by mechanical loading or by uridine 5'-triphosphate (UTP) stimulation. We hypothesized that mechanical loading might stimulate ecto-ATPase activity. Human tendon cells of surface epitenon (TSC) and internal compartment (TIF) were cyclically stretched (1 Hz, 0.035 strain, 2 h) with or without ATP. Aliquots of the supernatant fluids were collected at various time points, and ATP concentration (ATP) was determined by a luciferin-luciferase bioluminescence assay. Total RNA was isolated from TSC and TIF (three patients) and mRNA expression for ecto-nucleotidase was analyzed by RT-PCR. Human tendon cells secreted ATP in vitro (0.5-1 nM). Exogenous ATP was hydrolyzed within minutes. Mechanical load stimulated ATPase activity. ATP was hydrolyzed in mechanically loaded cultures at a significantly greater rate compared to no load controls. Tenocytes (TSC and TIF) expressed ecto-nucleotidase mRNA (ENTPD3 and ENPP1, ENPP2). These data suggest that motion may release ATP from tendon cells in vivo, where ecto-ATPase may also be activated to hydrolyze ATP quickly. Ecto-ATPase may act as a co-modulator in ATP load-signal modulation by regulating the half-life of extracellular purine nucleotides. The extracellular ATP/ATPase system may be important for tendon homeostasis by protecting tendon cells from responding to excessive load signals and activating injurious pathways. Copyright 2005 Wiley-Liss, Inc

  16. A procedure for combining acoustically induced and mechanically induced loads (first passage failure design criterion)

    NASA Technical Reports Server (NTRS)

    Crowe, D. R.; Henricks, W.

    1983-01-01

    The combined load statistics are developed by taking the acoustically induced load to be a random population, assumed to be stationary. Each element of this ensemble of acoustically induced loads is assumed to have the same power spectral density (PSD), obtained previously from a random response analysis employing the given acoustic field in the STS cargo bay as a stationary random excitation. The mechanically induced load is treated as either (1) a known deterministic transient, or (2) a nonstationary random variable of known first and second statistical moments which vary with time. A method is then shown for determining the probability that the combined load would, at any time, have a value equal to or less than a certain level. Having obtained a statistical representation of how the acoustic and mechanical loads are expected to combine, an analytical approximation for defining design levels for these loads is presented using the First Passage failure criterion.

  17. Development and Validation of a Bioreactor System for Dynamic Loading and Mechanical Characterization of Whole Human Intervertebral Discs in Organ Culture

    PubMed Central

    Walter, BA; Illien-Junger, S; Nasser, P; Hecht, AC; Iatridis, JC

    2014-01-01

    Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48 hours of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques. PMID:24725441

  18. The effect of elbow flexor fatigue on spine kinematics and muscle activation in response to sudden loading at the hands.

    PubMed

    Zwambag, Derek P; Freeman, Nikole E; Brown, Stephen H M

    2015-04-01

    Sudden loads, originating at either the hands or the feet, can cause injury to spine structures. As muscles are primarily responsible for stabilization following a perturbation, the effect of spine muscle fatigue in this context has been well investigated. However, the effect of fatigue of arm muscles, which can help control perturbations originating at the hands, on the spine is unknown. The purpose of this study was to determine if the magnitude of spine flexion or the pre-activation, reflex amplitude, and reflex latency of spine muscles were altered by elbow flexor fatigue during a sudden loading (6.8 kg) perturbation at the hands. Elbow flexor fatigue was induced by an isometric 30% maximal elbow flexion moment until failure. Results demonstrate that spine kinematics were not altered in the presence of elbow flexor fatigue. Small magnitude differences in trunk muscle pre- and peak activation indicate that the presence of elbow flexor fatigue does not necessitate substantially greater spine muscle action under the tested conditions. Despite fatigued elbow flexors, the arm muscles were sufficiently able to control the perturbation. Interestingly, 5/14 participants demonstrated altered reflex latencies in all observed muscles that lasted up to 10 min after the fatiguing task. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Association of Lis1 with outer arm dynein is modulated in response to alterations in flagellar motility

    PubMed Central

    Rompolas, Panteleimon; Patel-King, Ramila S.; King, Stephen M.

    2012-01-01

    The cytoplasmic dynein regulatory factor Lis1, which induces a persistent tight binding to microtubules and allows for transport of cargoes under high-load conditions, is also present in motile cilia/flagella. We observed that Lis1 levels in flagella of Chlamydomonas strains that exhibit defective motility due to mutation of various axonemal substructures were greatly enhanced compared with wild type; this increase was absolutely dependent on the presence within the flagellum of the outer arm dynein α heavy chain/light chain 5 thioredoxin unit. To assess whether cells might interpret defective motility as a “high-load environment,” we reduced the flagellar beat frequency of wild-type cells through enhanced viscous load and by reductive stress; both treatments resulted in increased levels of flagellar Lis1, which altered the intrinsic beat frequency of the trans flagellum. Differential extraction of Lis1 from wild-type and mutant axonemes suggests that the affinity of outer arm dynein for Lis1 is directly modulated. In cytoplasm, Lis1 localized to two punctate structures, one of which was located near the base of the flagella. These data reveal that the cell actively monitors motility and dynamically modulates flagellar levels of the dynein regulatory factor Lis1 in response to imposed alterations in beat parameters. PMID:22855525

  20. Effects of nitrogen deposition and empirical nitrogen critical loads for ecoregions of the United States

    USGS Publications Warehouse

    Pardo, L.H.; Fenn, M.E.; Goodale, C.L.; Geiser, L.H.; Driscoll, C.T.; Allen, E.B.; Baron, Jill S.; Bobbink, R.; Bowman, W.D.; Clark, C.M.; Emmett, B.; Gilliam, F.S.; Greaver, T.L.; Hall, S.J.; Lilleskov, E.A.; Liu, L.; Lynch, J.A.; Nadelhoffer, K.J.; Perakis, S.S.; Robin-Abbott, M. J.; Stoddard, J.L.; Weathers, K.C.; Dennis, R.L.

    2011-01-01

    Human activity in the last century has led to a significant increase in nitrogen (N) emissions and atmospheric deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the deposition of pollution that would be harmful to ecosystems is the determination of critical loads. A critical load is defined as the input of a pollutant below which no detrimental ecological effects occur over the long-term according to present knowledge. The objectives of this project were to synthesize current research relating atmospheric N deposition to effects on terrestrial and freshwater ecosystems in the United States, and to estimate associated empirical N critical loads. The receptors considered included freshwater diatoms, mycorrhizal fungi, lichens, bryophytes, herbaceous plants, shrubs, and trees. Ecosystem impacts included: (1) biogeochemical responses and (2) individual species, population, and community responses. Biogeochemical responses included increased N mineralization and nitrification (and N availability for plant and microbial uptake), increased gaseous N losses (ammonia volatilization, nitric and nitrous oxide from nitrification and denitrification), and increased N leaching. Individual species, population, and community responses included increased tissue N, physiological and nutrient imbalances, increased growth, altered root : shoot ratios, increased susceptibility to secondary stresses, altered fire regime, shifts in competitive interactions and community composition, changes in species richness and other measures of biodiversity, and increases in invasive species. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1-39 kg N.ha -1.yr -1, spanning the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, and trees. The critical load approach is an ecosystem assessment tool with great potential to simplify complex scientific information and communicate effectively with the policy community and the public. This synthesis represents the first comprehensive assessment of empirical critical loads of N for major ecoregions across the United States. ?? 2011 by the Ecological Society of America.

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