Dominant role of interface over knee angle for cushioning impact loading and regulating initial leg stiffness

For in vivo impact loadings administered under controlled initial conditions, it was hypothesized that larger initial knee angles (IKA) and softer impacting interfaces would reduce impact loading and initial leg stiffness. A human pendulum was used to deliver controlled impacts to the right foot of 21 subjects for three IKA (0, 20 and 40°) and three interfaces (barefoot, soft and hard EVA foams). The external impact force and the shock experienced by the subjects' shank were measured simultaneously with a wall mounted force platform and a skin mounted accelerometer, respectively. Stiffness of the leg was derived using impact velocity and wall reaction force data. The results disproved the role of the knee joint in regulating initial leg stiffness and provided only partial support for the hypothesized improved cushioning. Larger knee flexion at contact reduced impact force but increased the shock travelling throughout the shank. Conversely, softer interfaces produced sizable reductions in both initial leg stiffness and severity of the impact experienced by the lower limb. Force rate of loading was found to be highly correlated (r=0.95) to limb stiffness that was defined by the heel fat pad and interface deformations. These results would suggest that interface interventions are more likely to protect the locomotor system against impact loading than knee angle strategies.     

Normalizing and scaling of data to derive human response corridors from impact tests

It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed.     

Relationships of 35 lower limb muscles to height and body mass quantified using MRI

Skeletal muscle is the most abundant tissue in the body and serves various physiological functions including the generation of movement and support. Whole body motor function requires adequate quantity, geometry, and distribution of muscle. This raises the question: how do muscles scale with subject size in order to achieve similar function across humans? While much of the current knowledge of human muscle architecture is based on cadaver dissection, modern medical imaging avoids limitations of old age, poor health, and limited subject pool, allowing for muscle architecture data to be obtained in vivo from healthy subjects ranging in size. The purpose of this study was to use novel fast-acquisition MRI to quantify volumes and lengths of 35 major lower limb muscles in 24 young, healthy subjects and to determine if muscle size correlates with bone geometry and subject parameters of mass and height. It was found that total lower limb muscle volume scales with mass (R²=0.85) and with the height–mass product (R²=0.92). Furthermore, individual muscle volumes scale with total muscle volume (median R²=0.66), with the height–mass product (median R²=0.61), and with mass (median R²=0.52). Muscle volume scales with bone volume (R²=0.75), and muscle length relative to bone length is conserved (median s.d.=2.1% of limb length). These relationships allow for an arbitrary subject's individual muscle volumes to be estimated from mass or mass and height while muscle lengths may be estimated from limb length. The dataset presented here can further be used as a normative standard to compare populations with musculoskeletal pathologies.     

A method for quantifying the anterior load–displacement behavior of the human knee in both the low and high stiffness regions

The anterior load–displacement behavior of the human knee with an intact ACL is characterized by a very low stiffness region initially and a high stiffness region that develops as anterior load is increased. Although this behavior has been well recognized for some time, a method for quantitatively describing the behavior in these two regions based on limits of motion at specific values of anterior/posterior force has not yet been developed. Thus, the purposes of this study were to describe and justify such a method for measuring the laxity and stiffness in both of these regions in the intact knee.

Unique to this study, low stiffness and high stiffness laxities were computed based on three limits of motion for seven cadaveric knees tested at flexion angles ranging from 0° to 90°. Defining the reference position of the tibia relative to the femur, one limit was the 0 N posterior limit which was determined using a specially designed load cycle to reduce uncertainty in establishing a reference position. Defining the upper bound of the load–displacement curve, a second limit was the 225 N anterior limit. A third intermediate limit was the 45 N anterior limit, which was the load that represented the transition from the low stiffness to the high stiffness region. Stiffnesses corresponding to each of the two regions were computed using regression analysis and also estimated based on the laxities. Comparison between the computed and estimated stiffnesses demonstrated that the stiffnesses in both the low and high stiffness regions can be estimated reasonably accurately based on the laxities. Therefore, the 0 N posterior limit and the two laxities are the three quantities needed to describe the load–displacement behavior of the normal knee.     

Soft tissue artefacts of skin markers on the lower limb during cycling: Effects of joint angles and pedal resistance

Soft tissue artefacts (STA) are a major error source in skin marker-based measurement of human movement, and are difficult to eliminate non-invasively. The current study quantified in vivo the STA of skin markers on the thigh and shank during cycling, and studied the effects of knee angles and pedal resistance by using integrated 3D fluoroscopy and stereophotogrammetry. Fifteen young healthy adults performed stationary cycling with and without pedal resistance, while the marker data were measured using a motion capture system, and the motions of the femur and tibia/fibula were recorded using a bi-plane fluoroscopy-to-CT registration method. The STAs with respect to crank and knee angles over the pedaling cycle, as well as the within-cycle variations, were obtained and compared between resistance conditions. The thigh markers showed greater STA than the shank ones, the latter varying linearly with adjacent joint angles, the former non-linearly with greater within-cycle variability. Both STA magnitudes and within-cycle variability were significantly affected by pedal resistance (p < 0.05). The STAs appeared to be composed of one component providing the stable and consistent STA patterns and another causing their variations. Mid-segment markers experienced smaller STA ranges than those closer to a joint, but tended to have greater variations primarily associated with pedal resistance and muscle contractions. The current data will be helpful for a better choice of marker positions for data collection, and for developing methods to compensate for both stable and variation components of the STA.     

The response of the seated human to sinusoidal vibration and impact

Low back pain has been shown to occur more frequently among vehicle drivers than in representative control groups. Thus the response of the human to vibration and impact is of interest. This study investigated the response of the spine to both impact and sinusoidal excitation in either a relaxed or erect seated posture. The sinusoidal testing apparatus used was a resonating system consisting of two parallel wooden beams, simply supported, and the impact testing apparatus a bearing-guided, spring-suspended platform, struck from below. Ten subjects (5 males, 5 females) were evaluated using both methods. Transfer functions were compared at 2-4 Hz, 4-8 Hz and 8-16 Hz intervals using a sign test. Although in 24 comparisons of either test method (vibration or impact) or posture (erect or relaxed) where eleven showed differences significant at the p less than .05 level, only 2 out of 24 comparisons were the differences distinct enough to be significant (at the p less than .01 level). Both of these latter differences were due to test method while the subjects were sitting erect. In those instances where there were no significant differences due to test method, the impact method may be a viable replacement for the vibration test method. Where the levels of significance are higher (p less than .01 or p less than .05), further study of the magnitude of the differences is indicated and may reveal further insight into the seated individual as a system.     

大肠埃希菌脂多糖诱导的血小板降解及急性休克:O抗原在LPS诱导的免疫反应中的作用

目的探讨LPS中的0抗原部分与其它部分在血小板反应中的作用。方法给BALB／c小鼠注人大肠埃希菌野生株E．coli O8、O9、K-12（不含有O抗原）及2株重组变异的K-12株（携带编码O8、O9的O抗原rfb基因）。结果K-12的LPS引起血小板反应及急性休克能力较弱,O8及O9引起一定的反应,而这2种重组的LPS,即在K-12的LPS上带有O8或O9的O抗原．显示出极强的活性。静脉注入补体C5的阻止剂后,重组株LPS的作用消失了。而且在缺乏补体C5小鼠DBA／2中,重组的LPS能引起血小板的聚集但不能降解,也不能引起休克症状。结论诱导血小板反应及急性休克的能力依赖于LPS结构;O抗原及R核心抗原是表现活性的必要结构;LPS诱导的血小板反应及急性休克依赖补体系统。     

Effect of assumed stiffness and mass density on the impact response of the human chest using a three-dimensional FE model of the human body

The mass density, Young's modulus (E), tangent modulus (Et), and yield stress (sigma y) of the human ribs, sternum, internal organs, and muscles play important roles when determining impact responses of the chest associated with pendulum impact. A series of parametric studies was conducted using a commercially available three-dimensional finite element (FE) model, Total HUman Model for Safety (THUMS) of the whole human body, to determine the effect of changing these material properties on the predicted impact force, chest deflection, and the number of rib fractures and fractured ribs. Results from this parametric study indicate that the initial chest apparent stiffness was mainly influenced by the stiffness and mass density of the superficial muscles covering the torso. The number of rib fractures and fractured ribs was primarily determined by the stiffness of the ribcage. Similarly, the stiffness of the ribcage and internal organs contributed to the maximum chest deflection in frontal impact, while the maximum chest deflection for lateral impact was mainly affected by the stiffness of the ribcage. Additionally, the total mass of the whole chest had a moderately effect on the number of rib fractures.     

Transactivation of the epidermal growth factor receptor by heat shock protein 90 via Toll-like receptor 4 contributes to the migration of glioblastoma cells

Extracellular heat shock protein HSP90α was reported to participate in tumor cell growth, invasion, and metastasis formation through poorly understood signaling pathways. Herein, we show that extracellular HSP90α favors cell migration of glioblastoma U87 cells. More specifically, externally applied HSP90α rapidly induced endocytosis of EGFR. This response was accompanied by a transient increase in cytosolic Ca(2+) appearing after 1-3 min of treatment. In the presence of EGF, U87 cells showed HSP90α-induced Ca(2+) oscillations, which were reduced by the ATP/ADPase, apyrase, and inhibited by the purinergic P(2) inhibitor, suramin, suggesting that ATP release is requested. Disruption of lipid rafts with methyl β-cyclodextrin impaired the Ca(2+) rise induced by extracellular HSP90α combined with EGF. Specific inhibition of TLR4 expression by blocking antibodies suppressed extracellular HSP90α-induced Ca(2+) signaling and the associated cell migration. HSPs are known to bind lipopolysaccharides (LPSs). Preincubating cells with Polymyxin B, a potent LPS inhibitor, partially abrogated the effects of HSP90α without affecting Ca(2+) oscillations observed with EGF. Extracellular HSP90α induced EGFR phosphorylation at Tyr-1068, and this event was prevented by both the protein kinase Cδ inhibitor, rottlerin, and the c-Src inhibitor, PP2. Altogether, our results suggest that extracellular HSP90α transactivates EGFR/ErbB1 through TLR4 and a PKCδ/c-Src pathway, which induces ATP release and cytosolic Ca(2+) increase and finally favors cell migration. This mechanism could account for the deleterious effects of HSPs on high grade glioma when released into the tumor cell microenvironment.     

Climatic severity and the response to temperature elevation of Arctic aphids

• 1 Theory suggests that any given rise in temperature resulting from climate change will have its greatest effect on high Arctic ecosystems where growing seasons are short and temperatures low.
• 2 A small temperature rise, similar to that predicted for the middle of the next century, has profound effects on a population of the high Arctic, Dryas-feeding aphid Acyrthosiphon svalbardicum on Spitsbergen (Strathdee et al. 1993a).
• 3 Here comparative experiments on a closely related Dryas-feeding species, A. brevicorne, at two contrasting sub-Arctic sites are described. Together with the results from Spitsbergen these sites represent two colder sites (high Arctic and upland sub-Arctic) and one warmer site (lowland sub-Arctic).
• 4 Differential responses in aphid population density and overwintering egg production to temperature elevation support the hypothesis that the ecological effects are greatest at sites with the most severe climates; however, there is no similar gradient in advancement of host plant phenology with warming.

     

The effect of lower body positive pressure on the cardiovascular response to exercise in sedentary and endurance-trained persons with paraplegia

Exercise intolerance in persons with paraplegia (PARAS) is thought to be secondary to insufficient venous return and a subnormal cardiac output at a given oxygen uptake. However, these issues have not been resolved fully. This study utilized lower-body positive pressure (LBPP) as an intervention during arm crank exercise in PARAS in order to examine this issue. Endurance-trained (TP, n= 7) and untrained PARAS (UP, n= 10) with complete lesions between T6 and T12, and a control group consisting of sedentary able-bodied subjects (SAB, n= 10) were tested. UP and TP subjects demonstrated a diminished cardiac output (via CO₂ rebreathing) during exercise compared to SAB subjects. Peak oxygen uptake (V˙O_2peak) remained unchanged for all groups following LBPP. LBPP resulted in a significant decrease in heart rate (HR) in UP and TP (P≤0.05), but not SAB subjects. LBPP produced an insignificant increase in cardiac output (Q˙) and stroke volume (SV). The significant decrease in HR in both PARA groups may indicate a modest hemodynamic benefit of LBPP at higher work rates where circulatory sufficiency may be most compromised. We conclude that PARAS possess a diminished cardiac output during exercise compared to the able-bodied, and LBPP fails to ameliorate significantly their exercise response irrespective of the conditioning level. These results support previous observations of a lower cardiac output during exercise in PARAS, but indicate that lower-limb blood pooling may not be a primary limitation to arm exercise in paraplegia. Accepted: 11 December 1997     

Effect of different whole body hyperthermic sessions on the heat shock response in mice liver and brain

The apoptotic death of cardiomyocytes due to ischemia/reperfusion is one of the major complications of heart disease. Ischemia/reperfusion has been shown to lead to the activation of the stress-activated protein (SAP) kinases and the p38/reactivating kinase (p38/RK). In this study, the direct effect of an aqueous Flos carthami (FC) extract on SAP kinases was investigated. When isolated rat hearts were perfused by Langendorff mode with media containing FC extract prior to the induction of global ischemia and the subsequent reperfusion, SAP kinase activity was inhibited 95%. Untreated ischemic/reperfused hearts showed a 57% elevation in the activity of SAP kinase. The in vitro effect of these FC extracts on SAP kinase was also tested. At a concentration of 10 g/ml, the aqueous FC extract resulted in 50% inhibition of SAP kinase activity in ischemic heart tissue. Our results showed that FC affected both the interaction of SAP kinase with c-jun as well as the phosphotransferase reaction. These results clearly demonstrate that extracts from Flos carthami exerted inhibitory effects on SAP kinase. The administration of the FC extract may lead to a modulation of the apoptotic effect of SAP kinase activation induced during ischemia/reperfusion.     

Differential response of human and rodent cell lines to chemical inhibition of the repair of potentially lethal damage

Summary We have examined the effects of several classes of metabolic inhibitors on the repair of potentially lethal damage in density-inhibited cultures of two rodent and two human cell systems which differ in their growth characteristics. Aphidicolin, 1--d-arabinofuranosylcytosine (ara-C) and hydroxyurea showed no effect on PLD repair, whereas the effects of 9--d-arabinofuranosyladenine (ara-A) and 3-aminobenzamide (3-AB) were cell line dependent. For example, 3-AB suppressed PLD repair almost completely in CHO cells, but showed no inhibitory effects in human diploid fibroblasts. These results indicate that inhibitors of DNA replication and poly(ADP-ribose) synthesis are not efficient inhibitors of cellular recovery in irradiated cells and, moreover, that such effects may be cell line dependent.     

Modeling muscle activity to study the effects of footwear on the impact forces and vibrations of the human body during running

A previously developed mass-spring-damper model of the human body is improved in this paper, taking muscle activity into account. In the improved model, a nonlinear controller mimics the functionality of the Central Nervous System (CNS) in tuning the mechanical properties of the soft-tissue package. Two physiological hypotheses are used to determine the control strategies that are used by the controller. The first hypothesis (constant-force hypothesis) postulates that the CNS uses muscle tuning to keep the ground reaction force (GRF) constant regardless of shoe hardness, wherever possible. It is shown that the constant-force hypothesis can explain the existing contradiction about the effects of shoe hardness on the GRF during running. This contradiction is emerged from the different trends observed in the experiments on actual runners, and experiments in which the leg was fixed and exposed to impact. While the GRF is found to be dependent on shoe hardness in the former set of experiments, no such dependency was observed in the latter. According to the second hypothesis, the CNS keeps the level of the vibrations of the human body constant using muscle tuning. The results of the study show that this second control strategy improves the model such that it can correctly simulate the effects of shoe hardness on the vibrations of the human body during running.     

A novel approach to the problem of geographic allocation of environmental impact in Life Cycle Assessment and Material Flow Analysis

Life Cycle Assessment and Material Flow Analysis, in spite of their invaluable contribution to the investigation of the environmental performance of human-dominated processes, still fall short of properly addressing the issue of the geographic distribution of the potential environmental impacts, which often has wide-reaching environmental as well as political implications. An innovative allocation method based on matrix algebra is introduced here, in order to allow to split the calculated environmental impact indicators into fractions thereof which are geographically attributed to the different world regions. This is done on the basis of: (i) where the analyzed process takes place and (ii) where the directly and indirectly required fossil and nuclear fuels are sourced from (including those for electricity production). The method has been successfully tested on primary aluminium production, as a first case study.