Validation of a full body finite element model (THUMS) for running-type impacts to the lower extremity

The purpose of this study was to determine whether modifying an existing, highly biofidelic full body finite element model [total human model for safety (THUMS)] would produce valid amplitude and temporal shock wave characteristics as it travels proximally through the lower extremity. Modifying an existing model may be more feasible than developing a new model, in terms of cost, labour and expertise. The THUMS shoe was modified to more closely simulate the material properties of a heel pad. Relative errors in force and acceleration data from experimental human pendulum impacts and simulated THUMS impacts were 22% and 54%, respectively, across the time history studied. The THUMS peak acceleration was attenuated by 57.5% and took 19.7 ms to travel proximally along the lower extremity. Although refinements may be necessary to improve force and acceleration timing, the modified THUMS represented, to a certain extent, shock wave propagation and attenuation demonstrated by living humans under controlled impact conditions.     

In vivo function of the craniofacial haft: the interorbital "pillar"

The craniofacial haft resists forces generated in the face during feeding, but the importance of these forces for the form of the craniofacial haft remains to be determined. In vivo bone strain data were recorded from the medial orbital wall in an owl monkey (Aotus), rhesus macaques (Macaca mulatta), and a galago (Otolemur) during feeding. These data were used to determine whether: the interorbital region can be modeled as a simple beam under bending or shear; the face is twisting on the brain case during unilateral biting or mastication; the interorbital "pillar" is being axially compressed during incisor loading and both axially compressed and laterally bent during mastication; and the interorbital "pillar" transmits axial compressive forces from the toothrow to the braincase. The strain data reveal that the interorbital region cannot be modeled as a anteroposteriorly oriented beam bent superiorly in the sagittal plane during incision or mastication. The strain orientations recorded in the majority of experiments are concordant with those predicted for a short beam under shear, although the anthropoids displayed evidence of multiple loading regimes in the medial orbital wall. Strain orientation data corroborate the hypothesis that the strepsirrhine face is twisted during mastication. The hypothesis that the interorbital region is a member in a rigid frame subjected to axial compression during mastication receives some support. The hypothesis that the interorbital region is a member in a rigid frame subjected to lateral bending during mastication is supported by the epsilon1/absolute value epsilon2 ratio data but not by the strain orientation data. The timing of peak shear strains in the medial orbital wall of anthropoids does not bear a consistent relationship to the timing of peak shear strain in the mandibular corpus, suggesting that bite force is not the only external force influencing the medial orbital wall. Strain orientation data suggest the existence of two distinct loading regimes, possibly associated with masseter or medial pterygoid contraction. Regardless of the loading regime, all taxa showed low strain magnitudes in the medial orbital wall relative to the anterior root of the zygoma and the mandibular corpus. The strain gradients documented here and elsewhere suggest that, in anthropoids at least, local effects of external forces are more important than a single global loading regime. The low strain magnitudes in the medial orbital wall and in other thin bony plates around the orbit suggest that these structures are not optimally designed for resisting feeding forces. It is hypothesized that their function is to provide rigid support and protection for soft-tissue structures such as the nasal epithelium, the brain, meninges, and the eye and its adnexa. In contrast with the face of Otolemur, which appears to be subjected to a single predominant loading regime, anthropoids may experience different loading regimes in different parts of the face. This implies that the anthropoid and strepsirrhine facial skulls might be optimized for different functions.     

Comparison of knee injury threshold during tibial compression based on limb orientation in mice

Our previous studies used tibial compression overload to induce anterior cruciate ligament (ACL) rupture in mice, while others have applied similar or greater compressive magnitudes without injury. The causes of these differences in injury threshold are not known. In this study, we compared knee injury thresholds using a “prone configuration” and a “supine configuration” that differed with respect to hip, knee, and ankle flexion, and utilized different fixtures to stabilize the knee. Right limbs of female and male C57BL/6 mice were loaded using the prone configuration, while left limbs were loaded using the supine configuration. Mice underwent progressive loading from 2 to 20 N, or cyclic loading at 9 N or 14 N (n = 9–11/sex/loading method). Progressive loading with the prone configuration resulted in ACL rupture at an average of 10.2 ± 0.9 N for females and 11.4 ± 0.7 N for males. In contrast, progressive loading with the supine configuration resulted in ACL rupture in only 36% of female mice and 50% of male mice. Cyclic loading with the prone configuration resulted in ACL rupture after 15 ± 8 cycles for females and 24 ± 27 cycles for males at 9 N, and always during the first cycle for both sexes at 14 N. In contrast, cyclic loading with the supine configuration was able to complete 1,200 cycles at 9 N without injury for both sexes, and an average of 45 ± 41 cycles for females and 49 ± 25 cycles for males at 14 N before ACL rupture. These results show that tibial compression configurations can strongly affect knee injury thresholds during loading.     

Effects of Short-Distance Recreational Mushing on Oxytocin,Gastrin, and Creatinine Kinase in Sled Dogs

A considerable increase in creatinine kinase (CK) activity and gastrin hormone due to exercise has been observed in sled dogs during endurance mushing races; however, there have been no studies on sled dogs during recreational mushing. Although oxytocin hormone is involved in social behaviors and empathy, it has not been studied in sled dogs. This study aimed to assess changes in plasma CK activity, and gastrin and oxytocin concentrations in adult sled dogs used in touristic mushing in North Patagonia, Argentina. Blood samples were collected before, during, and after the winter season of 2017. Creatinine kinase activity measurement was done using an enzymatic assay. Hormone analyses were performed using commercial Enzyme-Linked InmunoSorbent Assay kits. Results showed an expected two-fold increase in CK activity during the winter, with recovering basal values after winter (< 400 UI/L), low and stable levels of gastrin (9.4 ± 8.8 pg/mL), and a slight increase in oxytocin (23%) after mushing activities. No evidence indicated gastrin alterations or muscular damage from touristic mushing, but an oxytocin increase would indicate a stimulation of the brain reward system.     

Injury risk prediction from computational simulations of ocular blast loading

A predictive Lagrangian–Eulerian finite element eye model was used to analyze 2.27 and 0.45 kg trinitrotoluene equivalent blasts detonated from 24 different locations. Free air and ground level blasts were simulated directly in front of the eye and at lateral offset locations with box, average, less protective, and more protective orbital anthropometries, resulting in 96 simulations. Injury risk curves were developed for hyphema, lens dislocation, retinal damage, and globe rupture from experimental and computational data to compute risk from corneoscleral stress and intra-ocular pressure computational outputs. Corneoscleral stress, intra-ocular pressure, and injury risks increased when the blast size was larger and located nearer to the eye. Risks ranged from 20–100 % for hyphema, 1–100 % for lens dislocation, 2–100 % for retinal damage, and 0–98 % for globe rupture depending on the blast condition. Orbital geometry affected the stresses, pressures, and associated ocular injury risks of the blast conditions simulated. Orbital geometries that more fully surrounded the eye such as the more protective orbit tended to produce higher corneoscleral stresses and compression of the eye against the surrounding rigid orbit contributing to high stresses as the blast wave propagated. However, the more protective orbit tended to produce lower intra-ocular pressures in comparison with the other three orbital geometries which may indicate that the more protective orbit inhibits propagation of the blast wave and reduces ocular loading. Results of this parametric computational study of ocular blast loading are valuable to the design of eye protection equipment and the mitigation of blast-related eye injuries.     

Climate,Topography, and Canopy Chemistry Exert Hierarchical Control Over Soil N Cycling in a Neotropical Lowland Forest

Nutrient availability varies substantially across lowland tropical forests and constrains their responses to global change. However, interactions among regional, landscape, and local controls of nutrient availability are poorly understood. In that context, we explored the effects of rainfall, topography, and canopy chemistry on nitrogen (N) cycling across the Osa Peninsula (Costa Rica). We sampled soils from catenas in regions receiving 3000 versus 5000 mm y^?1 rainfall. In both regions, we sampled catenas starting on narrow, knife-edged ridges, and in the less humid region we compared catenas starting on rapidly eroding knife-edged ridges to catenas with ridges consisting of slowly eroding terraces. On the stable terraces, we sampled soils from 0.25 ha plots with either high or low mean canopy N. In all sites, we measured metrics of long- (soil δ¹⁵N) and short-term (net nitrification, net N mineralization, and KCl-extractable N) N availability. Mean soil δ¹⁵N was elevated in the less humid region (3.8 ± 0.16 vs. 3.1 ± 0.14‰; P = 0.003). Within that region, mean δ¹⁵N was enriched by approximately 1‰ on stable terraces (5.3 ± 0.14‰) relative to nearby knife-edged ridges (4.0 ± 0.24‰; P < 0.001). Short-term N metrics did not vary with rainfall or topography (P > 0.05). By contrast, short-term soil N metrics differed under canopies with high versus low canopy N, but soil δ¹⁵N did not. These results illustrate the role of climate and topography as dominant drivers of long-term N cycling in the region, as well as the potential for canopy characteristics, which are likely determined by species composition in this system, to impose small-scale heterogeneity within those broader constraints. Overall, our work suggests the utility of a hierarchical framework for understanding how diverse drivers of nutrient status interact across space and time in tropical forests.     

Effect of pelvis impact angle on stresses at the femoral neck during falls

Improved understanding is required of how the mechanics of the fall affect hip fracture risk. We used a hip impact simulator to determine how peak stresses at the femoral neck were affected by pelvis impact angle, hip abductor muscle force, and use of a wearable hip protector.We simulated falls from standing (2 m/s impact velocity) involving initial hip abductor muscle forces of 700 or 300 N. Trials were acquired for impact to the lateral aspect of the greater trochanter, and impact to the pelvis rotated 5°, 10° and 15° anteriorly (positive) or posteriorly (negative). Measures were acquired with and without a commercially available hip protector. During trials, we measured three-dimensional forces with a load cell at the femoral neck, and derived peak compressive and tensile stresses.Peak compressive stress increased 37% (5.91 versus 4.31 MPa; p < 0.0005) and peak tensile stress increased 209% (2.31 versus 0.75 MPa; p < 0.0005) when the pelvis impact angle changed from 15° anterior to −15° posterior. For lateral impacts, the peak tensile and compressive stresses averaged 73% and 8% lower, respectively, in the 700 N than 300 N muscle force condition, but the effect was reversed for anteriolateral or posteriolateral impacts. The attenuation in peak compressive stress from the hip protector was greatest for posteriolateral impacts (−15 to −5°; 36–41%), and least for anteriolateral (+15°; 10%).These results clarify the effects on hip fracture risk during a fall of pelvis impact angle and muscle forces, and should inform the design of improved hip protectors.     

The use of artificial neural networks to reduce data collection demands in determining spine loading: a laboratory based analysis

The extensive data requirements of three-dimensional inverse dynamics and joint modelling to estimate spinal loading prevent the implementation of these models in industry and may hinder development of advanced injury prevention standards. This work examines the potential of feed forward artificial neural networks (ANNs) as a data reduction approach and compared predictions to rigid link and EMG-assisted models. Ten males and ten females performed dynamic lifts, all approaches were applied and comparisons of predicted joint moments and joint forces were evaluated. While the ANN under- predicted peak extension moments (p = 0.0261) and joint compression (p < 0.0001), predictions of cumulative extension moments (p = 0.8293) and cumulative joint compression (p = 0.9557) were not different. Therefore, the ANNs proposed may be used to obtain estimates of cumulative exposure variables with reduced input demands; however they should not be applied to determine peak demands of a worker's exposure.     

Classical hybrid Monte-Carlo simulation of the interconversion of hexabromocyclododecane stereoisomers

The interconversion of the six main stereoisomers of the flame retardant hexabromocyclododecane (HBCD) is investigated by means of statistical thermodynamics using classical force-fields. ( ± )-α-, ( ± )-β- and ( ± )-γ-HBCD interconvert by swapping of absolute configurations on the three different (BrHC–CHBr)-moieties. The approach avoids saddle-point energy computations, but relies on classical thermodynamic simulation and pursues three consecutive steps. First, the application of classical hybrid Monte-Carlo simulations for quantum mechanical processes is justified. Second, the problem of insufficient convergence properties of hybrid Monte-Carlo methods for the generation of low temperature canonical ensembles is solved by an interpolation approach. Third, it is shown how free energy differences among stereoisomers are derived and how they can be used for the computation of interconversion rates. The simulation results confirm the experimentally observed interconversion rates and correctly identify α-HBCD as a thermodynamical sink in the oscillating mixture of stereoisomers.     

Reaction of a human head/neck/torso system to shock

The purpose of this study is to predict human response to, and potential damage from, impact loading by using numerical and physical models to monitor the head and thoracic reactions, intervertebral disk pressures, muscle elongations, and some internal organ pressures. The numerical model consists of a three-dimensional lumped-parameter system of ten rigid bodies connected by nine intervertebral joints and 28 muscle pairs. The masses represent the head; cervical vertebrae C1-C2, C3-C4, C5-C6, C7-T1 (the first thoracic vertebra); the entire thorax; lumbar vertebrae L1-L2, L3, L4-L5; and the pelvis. The physical model consists of: a water-filled cadaver skull, held in position by attached ligaments; plastic skeletal components involving vertebrae, sternum, ribs and pelvis; silicon rubber intervertebral disks; fabric muscles and ligaments; and water-filled containers replicating the liver, spleen and kidneys. The pelvis of the model is affixed to a plate mounted on a sled that runs on a track. Loading is applied by deceleration from a given velocity that occurs due to the impact of the sled with a fixed aluminum block. Results from the numerical model are compared with corresponding experimental information from the physical structure. Good correlation was obtained in these comparisons up to about 200-250 ms after impact. The results indicate that the head, cervical muscles and disks in the lumbar region are subjected to the greatest force changes and thus are most likely to be injured.     

A novel structured bioreactor for solid-state fermentation

A novel patented solid-state bioreactor (251 L) with honeycomb loading device was designed and its performance was tested. First, this apparatus gave a 66.87 % of calculated loading coefficient (volume ratio), which was almost twofold compared with conventional fermenters. Next, considering the crucial effect of heat transfer on bed loading and microbial growth, the performance was validated by temperature variance during fermentation and spore viability of Bacillus cereus DM423. Air pressure pulsation or external water jacket was used to control temperature; the maximal temperature variation was 7.7 versus 19.8 °C, respectively during fermentation. The difference was mainly due to the continuous gas phase characterized by solid-state fermentation (SSF). The average living spores of (1.50 ± 0.07) × 10¹¹ cfu/g at 40 h obtained from the device was higher than (0.70 ± 0.03) × 10¹¹ cfu/g from flask at 48 h. The results indicated that this new loading bioreactor with air pressure pulsation could be a good prospect for industrialization of SSF employing bacterial cultures.     

Effects of body configuration on pelvic injury in backward fall simulation using 3D finite element models of pelvis–femur–soft tissue complex

Injuries due to backward fall apart from sideways fall are a major health problem, particularly among the aged populations. The objectives of this study was to evaluate the responses to changing body configurations (angle between the trunk and impacting floor as 0°, 15°, 45° and 80°) during backward fall, based on a previously developed CT-scan-derived 3D non-linear and non-homogeneous finite element (FE) model of pelvis–femur–soft tissue complex with simplified biomechanical representation of the whole body. Under constant impact energy, these FE models evaluated the pelvic injury situations on the basis of peak impact force (7.64–16.74 kN) and peak principal compressive strain (more than 1.5%), consistent with the clinically observed injuries (sacral insufficiency, coccydynia). Also the change in location of peak strain and increase in peak impact force for changing configurations from 0° to 80° indicated the effect of whole body inertia during backward fall. It was also concluded that the inclusion of sacro-iliac and acetabular cartilages in the above FE models will further reduce above findings marginally (9.2% for 15° fall). These quantifications would also be helpful for a better design and development of safety structures such as safety floor for the nursing home or home for the aged persons.     

Influence of the crash pulse shape on the peak loading and the injury tolerance levels of the neck in in vitro low-speed side-collisions

The aim of the present in vitro study was to investigate the effect of the crash pulse shape on the peak loading and the injury tolerance levels of the human neck. In a custom-made acceleration apparatus 12 human cadaveric cervical spine specimens, equipped with a dummy head, were subjected to a series of incremental side accelerations. While the duration of the acceleration pulse of the sled was kept constant at 120 ms, its shape was varied: Six specimens were loaded with a slowly increasing pulse, i.e. a low loading rate, the other six specimens with a fast increasing pulse, i.e. a high loading rate. The loading of the neck was quantified in terms of the peak linear and angular acceleration of the head, the peak shear force and bending moment of the lower neck and the peak translation between head and sled. The shape of the acceleration curve of the sled only seemed to influence the peak translation between head and sled but none of the other four parameters. The neck injury tolerance level for the angular acceleration of the head and for the bending moment of the lower neck was almost identical for both, the high and the low loading rate. In contrast, the injury tolerance level for the linear acceleration of the head and for the shear force of the lower neck was slightly higher for the low loading rate as compared to the high loading rate. For the translation between head and sled this difference was even statistically significant. Thus, if the shape of the crash pulse is not known, solely the peak bending moment of the lower neck and the peak angular acceleration of the head seem to be suitable predictors for the neck injury risk but not the peak shear force of the lower neck, the peak linear acceleration of the head and the translation between head and thorax.     

Effect of upper and lower extremity control strategies on predicted injury risk during simulated forward falls: a study in healthy young adults

Fall-related wrist fractures are common at any age. We used a seven-link, sagittally symmetric, biomechanical model to test the hypothesis that systematically alterations in the configuration of the body during a forward fall from standing height can significantly influence the impact force on the wrists. Movement of each joint was accomplished by a pair of agonist and antagonist joint muscle torque actuators with assigned torque-angle, torque-velocity, and neuromuscular latency properties. Proportional-derivative joint controllers were used to achieve desired target body segment configurations in the pre- andor postground contact phases of the fall. Outcome measures included wrist impact forces and whole-body kinetic energy at impact in the best, and worst, case impact injury risk scenarios. The results showed that peak wrist impact force ranged from less than 1 kN to more than 2.5 kN, reflecting a fourfold difference in whole-body kinetic energy at impact (from less than 40 J to more than 160 J) over the range of precontact hip and knee joint angles used at impact. A reduction in the whole-body kinetic energy at impact was primarily associated with increasing negative work associated with hip flexion. Altering upper extremity configuration prior to impact significantly reduced the peak wrist impact force by up to 58% (from 919 N to 2212 N). Increased peak wrist impact forces associated greater shoulder flexion and less elbow flexion. Increasing postcontact arm retraction can reduce the peak wrist impact force by 28% (from 1491 N to 1078 N), but postcontact hip and knee rotations had a relatively small effect on the peak wrist impact force (8% reduction; from 1411 N to 1303 N). In summary, the choice of the joint control strategy during a forward fall can significantly affect the risk of wrist injury. The most effective strategy was to increase the negative work during hip flexion in order to dissipate kinetic energy thereby reducing the loss in potential energy prior to first impact. Extended hip or elbow configurations should be avoided in order to reduce forearm impact forces.     

Robust human body model injury prediction in simulated side impact crashes

This study developed a parametric methodology to robustly predict occupant injuries sustained in real-world crashes using a finite element (FE) human body model (HBM). One hundred and twenty near-side impact motor vehicle crashes were simulated over a range of parameters using a Toyota RAV4 (bullet vehicle), Ford Taurus (struck vehicle) FE models and a validated human body model (HBM) Total HUman Model for Safety (THUMS). Three bullet vehicle crash parameters (speed, location and angle) and two occupant parameters (seat position and age) were varied using a Latin hypercube design of Experiments. Four injury metrics (head injury criterion, half deflection, thoracic trauma index and pelvic force) were used to calculate injury risk. Rib fracture prediction and lung strain metrics were also analysed. As hypothesized, bullet speed had the greatest effect on each injury measure. Injury risk was reduced when bullet location was further from the B-pillar or when the bullet angle was more oblique. Age had strong correlation to rib fractures frequency and lung strain severity. The injuries from a real-world crash were predicted using two different methods by (1) subsampling the injury predictors from the 12 best crush profile matching simulations and (2) using regression models. Both injury prediction methods successfully predicted the case occupant's low risk for pelvic injury, high risk for thoracic injury, rib fractures and high lung strains with tight confidence intervals. This parametric methodology was successfully used to explore crash parameter interactions and to robustly predict real-world injuries.     

A computational study of the EN 1078 impact test for bicycle helmets using a realistic subject-specific finite element head model

Abstract

In the present study, the free fall impact test in accordance with the EN1078 standard for certification of bicycle helmets is replicated using numerical simulations. The impact scenario is simulated using an experimentally validated, patient-specific head model equipped with and without a bicycle helmet. Head accelerations and intracranial biomechanical injury metrics during the impacts are recorded. It is demonstrated that wearing the bicycle helmet during the impact reduces biomechanical injury metrics, with the biggest reduction seen in the metric for skull fracture.     

The axial injury tolerance of the human foot/ankle complex and the effect of Achilles tension

Axial loading of the foot/ankle complex is an important injury mechanism in vehicular trauma that is responsible for severe injuries such as calcaneal and tibial pilon fractures. Axial loading may be applied to the leg externally, by the toepan and/or pedals, as well as internally, by active muscle tension applied through the Achilles tendon during pre-impact bracing. The objectives of this study were to investigate the effect of Achilles tension on fracture mode and to empirically model the axial loading tolerance of the foot/ankle complex. Blunt axial impact tests were performed on forty-three (43) isolated lower extremities with and without experimentally simulated Achilles tension. The primary fracture mode was calcaneal fracture in both groups. However, fracture initiated at the distal tibia more frequently with the addition of Achilles tension (p < 0.05). Acoustic sensors mounted to the bone demonstrated that fracture initiated at the time of peak local axial force. A survival analysis was performed on the injury data set using a Weibull regression model with specimen age, gender, body mass, and peak Achilles tension as predictor variables (R2 = 0.90). A closed-form survivor function was developed to predict the risk of fracture to the foot/ankle complex in terms of axial tibial force. The axial tibial force associated with a 50% risk of injury ranged from 3.7 kN for a 65 year-old 5th percentile female to 8.3 kN for a 45 year-old 50th percentile male, assuming no Achilles tension. The survivor function presented here may be used to estimate the risk of foot/ankle fracture that a blunt axial impact would pose to a human based on the peak tibial axial force measured by an anthropomorphic test device.     

The effect of asymmetrical body orientation during simulated forward falls on the distal upper extremity impact response of healthy people

The occurrence of distal upper extremity injuries resulting from forward falls (approximately 165,000 per year) has remained relatively constant for over 20 years. Previous work has provided valuable insight into fall arrest strategies, but only symmetric falls in body postures that do not represent actual fall scenarios closely have been evaluated. This study quantified the effect of asymmetric loading and body postures on distal upper extremity response to simulated forward falls. Twenty participants were suspended from the Propelled Upper Limb fall ARest Impact System (PULARIS) in different torso and leg postures relative to the ground and to the sagittal plane (0°, 30° and 45°). When released from PULARIS (hands 10 cm above surface, velocity 1 m/s), participants landed on two force platforms, one for each hand. Right forearm impact response was measured with distal (radial styloid) and proximal (olecranon) tri-axial accelerometers and bipolar EMG from seven muscles. Overall, the relative height of the torso and legs had little effect on the forces, or forearm response variables. Muscle activation patterns consistently increased from the start to the peak activation levels after impact for all muscles, followed by a rapid decline after peak. The impact forces and accelerations suggest that the distal upper extremity is loaded more medial-laterally during asymmetric falls than symmetric falls. Altering the direction of the impact force in this way (volar-dorsal to medial-lateral) may help reduce distal extremity injuries caused when landing occurs symmetrically in the sagittal plane as it has been shown that volar-dorsal forces increase the risk of injury.     

Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction

It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRβ1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; β-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.     

Membrane-based actuation for high-speed single molecule force spectroscopy studies using AFM

Atomic force microscopy (AFM)-based dynamic force spectroscopy of single molecular interactions involves characterizing unbinding/unfolding force distributions over a range of pulling speeds. Owing to their size and stiffness, AFM cantilevers are adversely affected by hydrodynamic forces, especially at pulling speeds >10 μm/s, when the viscous drag becomes comparable to the unbinding/unfolding forces. To circumvent these adverse effects, we have fabricated polymer-based membranes capable of actuating commercial AFM cantilevers at speeds ≥100 μm/s with minimal viscous drag effects. We have used FLUENT^®, a computational fluid dynamics (CFD) software, to simulate high-speed pulling and fast actuation of AFM cantilevers and membranes in different experimental configurations. The simulation results support the experimental findings on a variety of commercial AFM cantilevers and predict significant reduction in drag forces when membrane actuators are used. Unbinding force experiments involving human antibodies using these membranes demonstrate that it is possible to achieve bond loading rates ≥10⁶ pN/s, an order of magnitude greater than that reported with commercial AFM cantilevers and systems.