We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeli...We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeling. Whereas circular muscle tone generates radial closure pressure to create a local peristaltic closure wave, longitudinal muscle tone has two functions, one physiological with mechanical implications, and one purely mechanical. Each of these functions independently reduces the tension of individual circular muscle fibers to maintain closure as a consequence of shortening of longitudinal muscle locally coordinated with increasing circular muscle tone. The physiological function is deduced by combining basic laws of mechanics with concurrent measurements of intraluminal pressure from manometry, and changes in cross sectional muscle area from endoluminal ultrasound from which local longitudinal shortening (LLS) can be accurately obtained. The purely mechanical function of LLS was discovered from mathematical modeling of peristaltic esophageal transport with the axial wall motion generated by LLS. Physiologically, LLS concentrates circular muscle fibers where closure pressure is highest. However, the mechanical function of LLS is to reduce the level of pressure required to maintain closure. The combined physiological and mechanical consequences of LLS are to reduce circular muscle fiber tension and power by as much as 1/10 what would be requiredfor peristalsis without the longitudinal muscle layer, a tremendous benefit that may explain the existence of longitudinal muscle fiber in the gut. We also review what is understood of the role of longitudinal muscle in esophageal emptying, reflux and pathology.展开更多
Perlecan,a heparan sulfate proteoglycan,acts as a mechanical sensor for bone to detect external loading.Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome(SJS)and atten...Perlecan,a heparan sulfate proteoglycan,acts as a mechanical sensor for bone to detect external loading.Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome(SJS)and attenuates loading4nduced bone formation in perlecan deficient mice(Hypo).Considering that intracellular calcium[Ca2+]i is an ubiquitous messenger controlling numerous cellular processes including mechanotransduction,we hypothesized that perlecan deficiency impairs bone’s calcium signaling in response to loading.To test this,we performed real-time[Ca2+]i imaging on in situ osteocytes of adult murine tibiae under cyclic loading(8 N,Figure 1).Relative to wild type(WT),Hypo osteocytes showed decreases in the overall[Ca2+]i response rate(-58%),calcium peaks(-33%),cells with multiple peaks(-53%),peak magnitude(-6.8%),and recovery speed to baseline(-23%).RNA sequencing and pathway analysis of tibiae from mice subjected to one or seven days of unilateral loading demonstrated that perlecan deficiency significantly suppressed the calcium signaling,ECM-receptor interaction,and focal adhesion pathways following repetitive loading.Defects in the endoplasmic reticulum(ER)calcium cycling regulators such as Ryr1/ryanodine receptors and Atp2a1/Sercal calcium pumps were identified in Hypo bones.Taken together,impaired calcium signaling may contribute to bone’s reduced anabolic response to loading,underlying the osteoporosis risk for the SJS patients.展开更多
A modeling strategy to predict the ability of surgical clips to achieve mechanical hemostasis when applied to the cut edge of a thick and muscular tissue is presented in this work. Although such a model may have broad...A modeling strategy to predict the ability of surgical clips to achieve mechanical hemostasis when applied to the cut edge of a thick and muscular tissue is presented in this work. Although such a model may have broad utility in the design of hemostatic clips and other surgical and wound closure applications, our particular focus was on uterine closure following a Cesarean delivery. Mechanical closure of a blood vessel, which is the first step in the hemostatic process, is established when the compressive forces on the outer surface of a blood vessel are sufficient to overcome the local blood pressure and collapse the vessel. For thick tissue, forces applied to the tissue surface set up a stress distribution within the tissue that, if sufficient to mechanically close all vessels, will lead to cessation of local blood flow. The focus of the current work was on utilization of a planar and nonlinear finite element model to predict the pressure distribution within uterine tissue under the influence of hemostatic clips. After experimental model validation with a polymer tissue phantom, design curves were numerically developed, which consisted of the clip force necessary to achieve hemostasis for a given thickness tissue as well as the resulting deformed tissue thickness. Such curves could form the basis for a preliminary clip design, which would provide initial design guidance before more expensive experimental studies were required.展开更多
I. INTRODUCTION This article addresses three major topics that are important in deciding whether to codify evidence law and in designing an evidence code. First, the article sets out some of the positives and negative...I. INTRODUCTION This article addresses three major topics that are important in deciding whether to codify evidence law and in designing an evidence code. First, the article sets out some of the positives and negatives to codifying evidence law.展开更多
文摘We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeling. Whereas circular muscle tone generates radial closure pressure to create a local peristaltic closure wave, longitudinal muscle tone has two functions, one physiological with mechanical implications, and one purely mechanical. Each of these functions independently reduces the tension of individual circular muscle fibers to maintain closure as a consequence of shortening of longitudinal muscle locally coordinated with increasing circular muscle tone. The physiological function is deduced by combining basic laws of mechanics with concurrent measurements of intraluminal pressure from manometry, and changes in cross sectional muscle area from endoluminal ultrasound from which local longitudinal shortening (LLS) can be accurately obtained. The purely mechanical function of LLS was discovered from mathematical modeling of peristaltic esophageal transport with the axial wall motion generated by LLS. Physiologically, LLS concentrates circular muscle fibers where closure pressure is highest. However, the mechanical function of LLS is to reduce the level of pressure required to maintain closure. The combined physiological and mechanical consequences of LLS are to reduce circular muscle fiber tension and power by as much as 1/10 what would be requiredfor peristalsis without the longitudinal muscle layer, a tremendous benefit that may explain the existence of longitudinal muscle fiber in the gut. We also review what is understood of the role of longitudinal muscle in esophageal emptying, reflux and pathology.
基金supported by NIH grants ( P30GM103333,R01AR054385)supported partially by a core access award through NIH NIGMS IDeA Program grant ( P20GM103446)
文摘Perlecan,a heparan sulfate proteoglycan,acts as a mechanical sensor for bone to detect external loading.Deficiency of perlecan increases the risk of osteoporosis in patients with Schwartz-Jampel Syndrome(SJS)and attenuates loading4nduced bone formation in perlecan deficient mice(Hypo).Considering that intracellular calcium[Ca2+]i is an ubiquitous messenger controlling numerous cellular processes including mechanotransduction,we hypothesized that perlecan deficiency impairs bone’s calcium signaling in response to loading.To test this,we performed real-time[Ca2+]i imaging on in situ osteocytes of adult murine tibiae under cyclic loading(8 N,Figure 1).Relative to wild type(WT),Hypo osteocytes showed decreases in the overall[Ca2+]i response rate(-58%),calcium peaks(-33%),cells with multiple peaks(-53%),peak magnitude(-6.8%),and recovery speed to baseline(-23%).RNA sequencing and pathway analysis of tibiae from mice subjected to one or seven days of unilateral loading demonstrated that perlecan deficiency significantly suppressed the calcium signaling,ECM-receptor interaction,and focal adhesion pathways following repetitive loading.Defects in the endoplasmic reticulum(ER)calcium cycling regulators such as Ryr1/ryanodine receptors and Atp2a1/Sercal calcium pumps were identified in Hypo bones.Taken together,impaired calcium signaling may contribute to bone’s reduced anabolic response to loading,underlying the osteoporosis risk for the SJS patients.
文摘A modeling strategy to predict the ability of surgical clips to achieve mechanical hemostasis when applied to the cut edge of a thick and muscular tissue is presented in this work. Although such a model may have broad utility in the design of hemostatic clips and other surgical and wound closure applications, our particular focus was on uterine closure following a Cesarean delivery. Mechanical closure of a blood vessel, which is the first step in the hemostatic process, is established when the compressive forces on the outer surface of a blood vessel are sufficient to overcome the local blood pressure and collapse the vessel. For thick tissue, forces applied to the tissue surface set up a stress distribution within the tissue that, if sufficient to mechanically close all vessels, will lead to cessation of local blood flow. The focus of the current work was on utilization of a planar and nonlinear finite element model to predict the pressure distribution within uterine tissue under the influence of hemostatic clips. After experimental model validation with a polymer tissue phantom, design curves were numerically developed, which consisted of the clip force necessary to achieve hemostasis for a given thickness tissue as well as the resulting deformed tissue thickness. Such curves could form the basis for a preliminary clip design, which would provide initial design guidance before more expensive experimental studies were required.
文摘I. INTRODUCTION This article addresses three major topics that are important in deciding whether to codify evidence law and in designing an evidence code. First, the article sets out some of the positives and negatives to codifying evidence law.
