MEMS-Based Cantilever Sensor for Simultaneous Measurement of Mass and Magnetic Moment of Magnetic Particles

This study presents a measurement approach suitable for the simultaneous determination of both the mass mp and magnetic moment µp of magnetic particles deposited on a micro electro mechanical system (MEMS) resonant cantilever balance, which is operated in parallel to an external magnetic field-induced force gradient F′(z). Magnetic induction B(z) and its second spatial derivative δ2B/δz2 is realized, beforehand, through the finite element method magnetics (FEMM) simulation with a pair of neodymium permanent magnets configured in a face-to-face arrangement. Typically, the magnets are mounted in a magnet holder assembly designed and fabricated in-house. The resulting F′ lowers the calibrated intrinsic stiffness k0 of the cantilever to k0-F′, which can, thus, be obtained from a measured resonance frequency shift of the cantilever. The magnetic moment µp per deposited particle is determined by dividing F′ by δ2B/δz2 and the number of the attached monodisperse particles given by the mass-induced frequency shift of the cantilever. For the plain iron oxide particles (250 nm) and the magnetic polystyrene particles (2 µm), we yield µp of 0.8 to 1.5 fA m2 and 11 to 19 fA m2 compared to 2 fA m2 and 33 fA m2 nominal values, respectively.

Molecular Mechanisms of Muscle Tone Impairment under Conditions of Real and Simulated Space Flight

Kozlovskaya et al. [1] and Grigoriev et al. [2] showed that enormous loss of muscle stiffness (atonia) develops in humans under true (space flight) and simulated microgravity conditions as early as after the first days of exposure. This phenomenon is attributed to the inactivation of slow motor units and called reflectory atonia. However, a lot of evidence indicating that even isolated muscle or a single fiber possesses substantial stiffness was published at the end of the 20th century. This intrinsic stiffness is determined by the active component, i.e. the ability to form actin-myosin cross-bridges during muscle stretch and contraction, as well as by cytoskeletal and extracellular matrix proteins, capable of resisting muscle stretch. The main facts on intrinsic muscle stiffness under conditions of gravitational unloading are considered in this review. The data obtained in studies of humans under dry immersion and rodent hindlimb suspension is analyzed. The results and hypotheses regarding reduced probability of cross-bridge formation in an atrophying muscle due to increased interfilament spacing are described. The evidence of cytoskeletal protein (titin, nebulin, etc.) degradation during gravitational unloading is also discussed. The possible mechanisms underlying structural changes in skeletal muscle collagen and its role in reducing intrinsic muscle stiffness are presented. The molecular mechanisms of changes in intrinsic stiffness during space flight and simulated microgravity are reviewed.

On-Orbit Robotic Grasping of a Spent Rocket Stage: Grasp Stability Analysis and Experimental Results

The increased complexity of the tasks that on-orbit robots have to undertake has led to an increased need for manipulation dexterity. Space robots can become more dexterous by adopting grasping and manipulation methodologies and algorithms from terrestrial robots. In this paper, we present a novel methodology for evaluating the stability of a robotic grasp that captures a piece of space debris, a spent rocket stage. We calculate the Intrinsic Stiffness Matrix of a 2-fingered grasp on the surface of an Apogee Kick Motor nozzle and create a stability metric that is a function of the local contact curvature, material properties, applied force, and target mass. We evaluate the efficacy of the stability metric in a simulation and two real robot experiments. The subject of all experiments is a chasing robot that needs to capture a target AKM and pull it back towards the chaser body. In the V-REP simulator, we evaluate four grasping points on three AKM models, over three pulling profiles, using three physics engines. We also use a real robotic testbed with the capability of emulating an approaching robot and a weightless AKM target to evaluate our method over 11 grasps and three pulling profiles. Finally, we perform a sensitivity analysis to demonstrate how a variation on the grasping parameters affects grasp stability. The results of all experiments suggest that the grasp can be stable under slow pulling profiles, with successful pulling for all targets. The presented work offers an alternative way of capturing orbital targets and a novel example of how terrestrial robotic grasping methodologies could be extended to orbital activities.

Neurophysiological validation of simultaneous intrinsic and reflexive joint impedance estimates

Background People with brain or neural injuries, such as cerebral palsy or spinal cord injury, commonly have joint hyper-resistance. Diagnosis and treatment of joint hyper-resistance is challenging due to a mix of tonic and phasic contributions. The parallel-cascade (PC) system identification technique offers a potential solution to disentangle the intrinsic (tonic) and reflexive (phasic) contributions to joint impedance, i.e. resistance. However, a simultaneous neurophysiological validation of both intrinsic and reflexive joint impedances is lacking. This simultaneous validation is important given the mix of tonic and phasic contributions to joint hyper-resistance. Therefore, the main goal of this paper is to perform a group-level neurophysiological validation of the PC system identification technique using electromyography (EMG) measurements. Methods Ten healthy people participated in the study. Perturbations were applied to the ankle joint to elicit reflexes and allow for system identification. Participants completed 20 hold periods of 60 seconds, assumed to have constant joint impedance, with varying magnitudes of intrinsic and reflexive joint impedances across periods. Each hold period provided a paired data point between the PC-based estimates and neurophysiological measures, i.e. between intrinsic stiffness and background EMG, and between reflexive gain and reflex EMG. Results The intrinsic paired data points, with all subjects combined, were strongly correlated, with a range of $$r = [0.87\ 0.91]$$ r = [ 0.87 0.91 ] in both ankle plantarflexors and dorsiflexors. The reflexive paired data points were moderately correlated, with $$r = [0.64\ 0.69]$$ r = [ 0.64 0.69 ] in the ankle plantarflexors only. Conclusion An agreement with the neurophysiological basis on which PC algorithms are built is necessary to support its clinical application in people with joint hyper-resistance. Our results show this agreement for the PC system identification technique on group-level. Consequently, these results show the validity of the use of the technique for the integrated assessment and training of people with joint hyper-resistance in clinical practice.

Measurement of the Bio-Mechanical Properties of Two Different Feeder Layer Cells

Introduction: We here present our findings on 2 types of feeder layers, one composed of mouse embryonic fibroblasts (MEF) and the second one of mouse skeletal myoblasts (C2Cl2) feeder cells. Methods: The 2 feeder layers present a dramatic variance of intrinsic stiffness (142.68 ± 17.21 KPa and 45.78 ± 9.81 KPa, respectively). Results and Conclusion: This information could be used for a better understanding of cells and cell microenvironment mechano-physical characteristics that are influencing stem cell commitment, in order to develop a suitable engineered tissue for cardiac and skeletal muscle repair and a bio-actuator.

SPATIAL ORGANIZATION OF TRANSCRIBED EUKARYOTIC GENES

SUMMARYDespite the well established role of nuclear organization in the regulation of gene expression, little is known about the reverse: how transcription shapes the spatial organization of the genome. In particular, given the relatively small sizes of genes and the limited resolution of light microscopy, the structure and spatial arrangement of a single transcribed gene are still poorly understood. Here, we make use of several long highly expressed mammalian genes and demonstrate that they form Transcription Loops (TLs) with polymerases moving along the loops and carrying nascent RNAs that undergo co-transcriptional splicing. TLs dynamically modify their harboring loci and extend into the nuclear interior suggesting an intrinsic stiffness. Both experimental evidence and polymer modeling support the hypothesis that TL stiffness is caused by the dense decoration of transcribed genes with multiple voluminous nascent RNPs. We propose that TL formation is a universal principle of eukaryotic gene expression.

Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery

BACKGROUND Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat. METHODS Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology. RESULTS Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall–lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats’ endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition. CONCLUSIONS Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD.

Patterns of muscle activation and modulation of ankle intrinsic stiffness in different postural operating conditions

Intrinsic stiffness describes the dynamic relationship between imposed angular perturbations to a joint and the resulting torque response, due to intrinsic mechanical properties of muscles and joint, and inertia of the limbs. Recently, we showed that ankle intrinsic stiffness changes substantially with sway in normal standing. In the present study, we documented how ankle intrinsic stiffness changes with postural operating conditions. Subjects stood on an apparatus while subjected to ankle position perturbations in five conditions: normal standing, toe-up and toe-down standing, and backward and forward lean. In each condition, ankle intrinsic stiffness was estimated while its modulation with sway was accounted for. The results demonstrated that ankle intrinsic stiffness varies widely, from 0.08 to 0.75 of critical stiffness, across postural operating conditions; however, it is always smaller than the critical stiffness. Therefore, other contributions are necessary to ensure stable standing. The mean intrinsic stiffness was highest in forward lean and lowest in backward lean. Moreover, within each operating condition, the intrinsic stiffness changed with center-of-pressure position in one of three ways, each associated with a distinct muscle activation pattern; these include 1) monotonically increasing stiffness-center of pressure relation, associated with a progressive increase in triceps surae activation, 2) decreasing-increasing stiffness-center of pressure relation, associated with initial activation of tibialis anterior and later activation of triceps surae, and 3) monotonically decreasing stiffness-center of pressure relation, associated with decreasing activation of tibialis anterior. Thus intrinsic stiffness varies greatly within and across postural operating conditions, and a correct understanding of postural control requires accounting for such variations. NEW & NOTEWORTHY Ankle intrinsic stiffness changes with sway in normal standing. We quantified such changes in different postural operating conditions and demonstrated that the intrinsic stiffness changes in a manner associated with different activation patterns of ankle plantarflexors and dorsiflexors, emerging in different operating conditions. Large modulations of the intrinsic stiffness within and across postural operating conditions show that the stiffness importance and contribution change and must be accounted for in the study of postural control.

C-terminal tail polyglycylation and polyglutamylation alter microtubule mechanical properties

ABSTRACTMicrotubules are biopolymers that perform diverse cellular functions. The regulation of microtubule behavior occurs in part through post-translational modification of both the α- and β- subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and glutamate residues to the disordered C-terminal tails of tubulin. Due to their prevalence in stable, high stress cellular structures such as cilia, we sought to determine if these modifications alter the intrinsic stiffness of microtubules. Here we describe the purification and characterization of differentially-modified pools of tubulin from Tetrahymena thermophila. We found that glycylation on the α-C-terminal tail is a key determinant of microtubule stiffness, but does not affect the number of protofilaments incorporated into microtubules. We measured the dynamics of the tail peptide backbone using nuclear magnetic resonance spectroscopy. We found that the spin-spin relaxation rate (R2) showed a pronounced decreased as a function of distance from the tubulin surface for the α-tubulin tail, indicating that the α-tubulin tail interacts with the dimer surface. This suggests that the interactions of the α-C-terminal tail with the tubulin body contributes to the stiffness of the assembled microtubule, providing insight into the mechanism by which glycylation and glutamylation can alter microtubule mechanical properties.SIGNIFICANCEMicrotubules are regulated in part by post-translational modifications including the heterogeneous addition of glycine and glutamate residues to the C-terminal tails. By producing and characterizing differentially-modified tubulin, this work provides insight into the molecular mechanisms of how these modifications alter intrinsic microtubule properties such as flexibility. These results have broader implications for mechanisms of how ciliary structures are able to function under high stress.