nils-herrmann/clean_scirepeval huggingface dataset:
Dynamics and 3D organization of secretory organelles of Toxoplasma gondii.
Venue: Journal of structural biology

Micronemes, rhoptries and dense granules are secretory organelles of Toxoplasma gondii crucial for host cell invasion and formation of the parasitophorous vacuole (PV). We examined whether their relative volumes change during the intracellular cycle. Stereological analysis of random ultrathin sections taken at 5min of interaction, 7 and 24h post-infection demonstrated that the relative volume of each type of organelle decreases just after the respective peak of secretion. Micronemes are radially arranged below the polar ring, while rhoptries converge to but only a few reach the inside of the conoid. In contrast to the apical and polarized organelles, dense granules were found scattered throughout the cytoplasm, with no preferential location in the parasite cell body. Extensive observation of random sections indicated that each organelle probably secretes in a different region. Micronemes secrete just below the posterior ring and probably require that the conoid is extruded. The rhoptries passing through the conoid secrete at a porosome-like point at the most apical region. Dense granules secrete laterally, probably at fenestrations in the inner membrane complex. Immunocytochemistry showed that there are no subpopulations of rhoptries or dense granules, as a single organelle can contain more than one kind of its specific proteins. The vacuolar-like profiles observed at the apical portion of parasites just after invasion were confirmed to be empty rhoptries, as they were positively labeled for rhoptry proteins. These findings contribute for a better understanding of the essential behavior of secretory organelles.
Evolutionary bidirectional expansion for the tracing of alpha helices in cryo-electron microscopy reconstructions.
Venue: Journal of structural biology

Cryo-electron microscopy (cryo-EM) enables the imaging of macromolecular complexes in near-native environments at resolutions that often permit the visualization of secondary structure elements. For example, alpha helices frequently show consistent patterns in volumetric maps, exhibiting rod-like structures of high density. Here, we introduce VolTrac (Volume Tracer) - a novel technique for the annotation of alpha-helical density in cryo-EM data sets. VolTrac combines a genetic algorithm and a bidirectional expansion with a tabu search strategy to trace helical regions. Our method takes advantage of the stochastic search by using a genetic algorithm to identify optimal placements for a short cylindrical template, avoiding exploration of already characterized tabu regions. These placements are then utilized as starting positions for the adaptive bidirectional expansion that characterizes the curvature and length of the helical region. The method reliably predicted helices with seven or more residues in experimental and simulated maps at intermediate (4-10Å) resolution. The observed success rates, ranging from 70.6% to 100%, depended on the map resolution and validation parameters. For successful predictions, the helical axes were located within 2Å from known helical axes of atomic structures.
Towards an atlas of mammalian cell ultrastructure by cryo soft X-ray tomography.
Venue: Journal of structural biology

We provide a catalog of 3D cryo soft X-ray tomography (cryo-SXT) images obtained from ∼6 to 12μm thick mouse adenocarcinoma cells. Included are multiple representative images of nuclei, nucleoli, nuclear membrane, nuclear membrane channels, mitochondria, lysosomes, endoplasmic reticulum, filaments and plasma membrane, plus three structures not previously described by cryo-SXT, namely Golgi, microvilli and nuclear-membrane blebs. Sections from the 3D cryo-SXT tomograms for all the preceding structures closely resemble those seen by thin-section transmission electron microscopy (TEM). Some structures such as nuclear-membrane channels and nuclear-membrane blebs are more easily detected by cryo-SXT than TEM most likely due to their better contrast and cellular preservation in cryo-SXT combined with the ability to rapidly locate these structures within a full 3D image. We identify and discuss two current limitations in cryo-SXT: variability in image quality and difficulties in detecting weaker contrast structures such as chromatin and various nuclear bodies. Progress on these points is likely to come from the solution of several technical problems in image acquisition, plus the implementation of advanced cryo soft X-ray microscopy approaches such as phase contrast or optical sectioning.
Crystal structures of salicylate 1,2-dioxygenase-substrates adducts: A step towards the comprehension of the structural basis for substrate selection in class III ring cleaving dioxygenases.
Venue: Journal of structural biology

The crystallographic structures of the adducts of salicylate 1,2-dioxygenase (SDO) with substrates salicylate, gentisate and 1-hydroxy-2-naphthoate, obtained under anaerobic conditions, have been solved and analyzed. This ring fission dioxygenase from the naphthalenesulfonate-degrading bacterium Pseudaminobacter salicylatoxidans BN12, is a homo-tetrameric class III ring-cleaving dioxygenase containing a catalytic Fe(II) ion coordinated by three histidine residues. SDO is markedly different from the known gentisate 1,2-dioxygenases or 1-hydroxy-2-naphthoate dioxygenases, belonging to the same class, because of its unique ability to oxidatively cleave salicylate, gentisate and 1-hydroxy-2-naphthoate. The crystal structures of the anaerobic complexes of the SDO reveal the mode of binding of the substrates into the active site and unveil the residues which are important for the correct positioning of the substrate molecules. Upon binding of the substrates the active site of SDO undergoes a series of conformational changes: in particular Arg127, His162, and Arg83 move to make hydrogen bond interactions with the carboxyl group of the substrate molecules. Unpredicted concerted displacements upon substrate binding are observed for the loops composed of residues 40-43, 75-85, and 192-198 where several aminoacidic residues, such as Leu42, Arg79, Arg83, and Asp194, contribute to the closing of the active site together with the amino-terminal tail (residues 2-15). Differences in substrate specificity are controlled by several residues located in the upper part of the substrate binding cavity like Met46, Ala85, Trp104, and Phe189, although we cannot exclude that the kinetic differences observed could also be generated by concerted conformational changes resulting from amino-acid mutations far from the active site.
Automatic alignment and reconstruction of images for soft X-ray tomography.
Venue: Journal of structural biology

Soft X-ray tomography (SXT) is a powerful imaging technique that generates quantitative, 3D images of the structural organization of whole cells in a near-native state. SXT is also a high-throughput imaging technique. At the National Center for X-ray Tomography (NCXT), specimen preparation and image collection for tomographic reconstruction of a whole cell require only minutes. Aligning and reconstructing the data, however, take significantly longer. Here we describe a new component of the high throughput computational pipeline used for processing data at the NCXT. We have developed a new method for automatic alignment of projection images that does not require fiducial markers or manual interaction with the software. This method has been optimized for SXT data sets, which routinely involve full rotation of the specimen. This software gives users of the NCXT SXT instrument a new capability - virtually real-time initial 3D results during an imaging experiment, which can later be further refined. The new code, Automatic Reconstruction 3D (AREC3D), is also fast, reliable, and robust. The fundamental architecture of the code is also adaptable to high performance GPU processing, which enables significant improvements in speed and fidelity.
The effect of a novel gait retraining device on lower limb kinematics and muscle activation in healthy adults.
Venue: Journal of biomechanics

The Re-Link Trainer (RLT) is a modified walking frame with a linkage system designed to apply a non-individualized kinematic constraint to normalize gait trajectory of the left limb. The premise behind the RLT is that a user's lower limb is constrained into a physiologically normal gait pattern, ideally generating symmetry across gait cycle parameters and kinematics. This pilot study investigated adaptations in the natural gait pattern of healthy adults when using the RLT compared to normal overground walking. Bilateral lower limb kinematic and electromyography data were collected while participants walked overground at a self-selected speed, followed by walking in the RLT. A series of 2-way analyses of variance examined between-limb and between-condition differences. Peak hip extension and knee flexion were reduced bilaterally when walking in the RLT. Left peak hip extension occurred earlier in the gait cycle when using the RLT, but later for the right limb. Peak hip flexion was significantly increased and occurred earlier for the constrained limb, while peak plantarflexion was significantly reduced. Peak knee flexion and plantarflexion in the right limb occurred later when using the RLT. Significant bilateral reductions in peak electromyography amplitude were evident when walking in the RLT, along with a significant shift in when peak muscle activity was occurring. These findings suggest that the RLT does impose a significant constraint, but generates asymmetries in lower limb kinematics and muscle activity patterns. The large interindividual variation suggests users may utilize differing motor strategies to adapt their gait pattern to the imposed constraint.
Computation of the role of kinetics, kinematics, posterior tibial slope and muscle cocontraction on the stability of ACL-deficient knee joint at heel strike - Towards identification of copers from non-copers.
Venue: Journal of biomechanics

Rupture of anterior cruciate ligament (ACL) undermines normal activity and function of the knee joint and places it at higher risk of re-injury and degeneration. ACL reconstruction surgery neither necessarily ensures return to pre-injury activities nor alleviates risk of long-term degeneration. Here in this computational investigation of a lower-extremity hybrid model at heel strike (HS) of gait, we search for factors that influence the stability of the joint and hence the distinct performances between post-ACL injury copers and non-copers. Due to the very unstable state of the joint under the mean gait input data, joint rotations-moments, posterior tibial slope (PTS), and cocontraction were altered within the reported data in the literature and the effects on the joint stability (anterior tibial translation (ATT) and critical muscle stiffness coefficient (qcr)) were investigated. Results indicate that, in presence of both a small extension moment (0.1 or 0.2 Nm/kg) and a flexion rotation (∼5-8°), ACL-deficient (ACL-D) knee joint stability substantially improves to levels computed in the pre-injury intact joint. In addition, low cocontraction levels of 1-3% (in hamstrings and quads only and not in gastrocnemii) and reduced PTS (by 5°) further improve ACL-D joint stability. Therefore for a stable joint with ATT < 3 mm and qcr < 25 similar to those in the intact knee at HS, higher flexion angles (>5°) and a small extension moment (∼0.1-0.2 Nm/kg) (i.e., higher activity in hamstrings than quads) are required. A lower posterior tibial slope (by 5°) and a small minimum cocontraction level (1-3%) in hamstrings and quads (but not in gastrocnemii) are also beneficial. These results identify mechanisms likely in play at HS in gait of copers when compared to non-copers.
The effect of follower load on the intersegmental coupled motion characteristics of the human thoracic spine: An in vitro study using entire rib cage specimens.
Venue: Journal of biomechanics

The mechanical coupling behaviour of the thoracic spine is still not fully understood. For the validation of numerical models of the thoracic spine, however, the coupled motions within the single spinal segments are of importance to achieve high model accuracy. In the present study, eight fresh frozen human thoracic spinal specimens (C7-L1, mean age 54 ± 6 years) including the intact rib cage were loaded with pure bending moments of 5 Nm in flexion/extension (FE), lateral bending (LB), and axial rotation (AR) with and without a follower load of 400 N. During loading, the relative motions of each vertebra were monitored. Follower load decreased the overall ROM (T1-T12) significantly (p < 0.01) in all primary motion directions (extension: -46%, left LB: -72%, right LB: -72%, left AR: -26%, right AR: -26%) except flexion (-36%). Substantial coupled motion was found in lateral bending with ipsilateral axial rotation, which increased after a follower load was applied, leading to a dominant axial rotation during primary lateral bending, while all other coupled motions in the different motion directions were reduced under follower load. On the monosegmental level, the follower load especially reduced the ROM of the upper thoracic spine from T1-T2 to T4-T5 in all motion directions and the ROM of the lower thoracic spine from T9-T10 to T11-T12 in primary lateral bending. The facet joints, intervertebral disc morphologies, and the sagittal curvature presumably affect the thoracic spinal coupled motions depending on axial compressive preloading. Using these results, the validation of numerical models can be performed more accurately.
Biomechanical analysis of fluid percussion model of brain injury.
Venue: Journal of biomechanics

Fluid percussion injury (FPI) is a widely used experimental model for studying traumatic brain injury (TBI). However, little is known about how the brain mechanically responds to fluid impacts and how the mechanical pressures/strains of the brain correlate to subsequent brain damage for rodents during FPI. Hence, we developed a numerical approach to simulate FPI experiments on rats and characterize rat brain pressure/strain responses at a high resolution. A previous rat brain model was improved with a new hexahedral elements-based skull model and a new cerebrospinal fluid (CSF) layer. We validated the numerical model against experimentally measured pressures from FPI. Our results indicated that brain tissues under FPI experienced high pressures, which were slightly lower (10-20%) than input saline pressure. Interestingly, FPI was a mixed focus- and diffuse-type injury model with highest strains (12%) being concentrated in the ipsilateral cortex under the fluid-impact site and diffuse strains (5-10%) being spread to the entire brain, which was different from controlled cortical impact in which high strains decreased gradually away from the impact site.
A subject-specific finite element musculoskeletal framework for mechanics analysis of a total knee replacement.
Venue: Journal of biomechanics

Concurrent use of finite element (FE) and musculoskeletal (MS) modeling techniques is capable of considering the interactions between prosthetic mechanics and subject dynamics after a total knee replacement (TKR) surgery is performed. However, it still has not been performed in terms of favorable prediction accuracy and systematic experimental validation. In this study, we presented a methodology to develop a subject-specific FE-MS model of a human right lower extremity including the interactions among the subject-specific MS model, the knee joint model with ligament bundles, and the deformable FE prosthesis model. In order to evaluate its accuracy, the FE-MS model was compared with a traditional hinge-constraint MS model and experimentally verified over a gait cycle. Both models achieved good temporal agreement between the predicted muscle force and the electromyography results, though the magnitude on models is different. A higher predicted accuracy, quantified by the root-mean-square error (RMSE) and the squared Pearson correlation coefficient (r2), was found in the FE-MS model (RMSE = 177.2 N, r2 = 0.90) when compared with the MS model (RMSE = 224.1 N, r2 = 0.81) on the total tibiofemoral contact force. The contact mechanics, including the contact area, pressure, and stress were synchronously simulated, and the maximum contact pressure, 22.06 MPa, occurred on the medial side of the tibial insert without exceeding the yield strength of the ultra-high-molecular-weight polyethylene, 24.79 MPa. The approach outlines an accurate knee joint biomechanics analysis and provides an effective method of applying individualized prosthesis design and verification in TKR.
Predicting foot placement for balance through a simple model with swing leg dynamics.
Venue: Journal of biomechanics

Stepping is one important strategy to restore balance against external perturbations. Although current literature have proposed models to predict the recovery foot placement, swing leg actuation is rarely taken into account. In this paper, we combine the capturability-based analysis with swing leg dynamics and seek to contribute to the following problem: for a biped system recovering balance from external perturbations, how to choose a step position and duration in minimizing swing actuation cost? We expand the linear inverted pendulum model with an actuated linear pendulum mounted on the pelvis, the addition of which is proposed to describe the swing leg dynamics. The closed-form expression of swing actuation with constraints is derived from the explicit formulations of the pelvis and swing foot motion. We calculate the optimal step position and duration to minimize swing cost under various perturbations. Results show that the optimal step duration keeps constant, while the optimal step position is linearly proportional to the magnitude of perturbations. Such findings match well with experimental data from ten subjects delivered with waist-perturbations. These current results demonstrate that our proposed model with swing dynamics suggests an effective alternative to predict recovery foot placement of biped systems following unexpected perturbations.
Development of a dynamic index finger and thumb model to study impairment.
Venue: Journal of biomechanics

Modeling of the human hand provides insight for explaining deficits and planning treatment following injury. Creation of a dynamic model, however, is complicated by the actions of multi-articular tendons and their complex interactions with other soft tissues in the hand. This study explores the creation of a musculoskeletal model, including the thumb and index finger, to explore the effects of muscle activation deficits. The OpenSim model utilizes physiological axes of rotation at all joints, passive joint torques, and appropriate moment arms. The model was validated through comparison with kinematic and kinetic experimental data. Simulated fingertip forces resulting from modeled musculotendon loading largely fell within one standard deviation of experimental ranges for most index finger and thumb muscles, although agreement in the sagittal plane was generally better than for the coronal plane. Input of experimentally obtained electromyography data produced the expected simulated finger and thumb motion. Use of the model to predict the effects of activation deficits on pinch force production revealed that the intrinsic muscles, especially first dorsal interosseous (FDI) and adductor pollicis (ADP), had a substantial impact on the resulting fingertip force. Reducing FDI activation, such as might occur following stroke, altered fingertip force direction by up to 83° for production of a dorsal fingertip force; reducing ADP activation reduced force production in the thumb by up to 62%. This validated model can provide a means for evaluating clinical interventions.
Validation of model-predicted tibial tray-synthetic bone relative motion in cementless total knee replacement during activities of daily living.
Venue: Journal of biomechanics

As fixation of cementless total knee replacement components during the first 4-6 weeks after surgery is crucial to establish bony ingrowth into the porous surface, several studies have quantified implant-bone micromotion. Relative motion between the tray and bone can be measured in vitro, but the full micromotion contour map cannot typically be accessed experimentally. Finite element models have been employed to estimate the full micromotion map, but have not been directly validated over a range of loading conditions. The goal of this study was to develop and validate computational models for the prediction of tray-bone micromotion under simulated activities of daily living. Gait, stair descent and deep knee bend were experimentally evaluated on four samples of a cementless tibial tray implanted into proximal tibial Sawbones™ constructs. Measurements of the relative motion between the tray and the anterior cortical shell were collected with digital image correlation and used to validate a finite element model that replicated the experiment. Additionally, a probabilistic analysis was performed to account for experimental uncertainty and determine model sensitivity to alignment and frictional parameters. The finite element models were able to distinguish between activities and capture the experimental trends. Best-matching simulations from the probabilistic analysis matched measured displacement with an average root mean square (RMS) difference of 14.3 µm and Pearson-product correlation of 0.93, while the mean model presented an average RMS difference of 27.1 µm and a correlation of 0.8. Maximum deviations from average experimental measurements were 40.5 and 87.1 µm for the best-matching and average simulations, respectively. The computational pipeline developed in this study can facilitate and enhance pre-clinical assessment of novel implant components.
On modeling wave dispersion characteristics of protein lipid nanotubules.
Venue: Journal of biomechanics

In this article, wave propagation characteristics of protein lipid nanotubules are covered with respect to scale effects utilizing nonlocal strain gradient theory. The structure is supposed to be modeled as a simply supported beam and the kinematic relations are derived based on the classical beam theory (CBT). Implementing an energy based approach, the Euler-Lagrange equations of the lipid tubules are obtained. Moreover, the final governing equations are solved analytically to achieve the wave frequency and phase velocity of propagated waves. Influences of small size and wave number on the wave dispersion responses of lipid nanotubules are shown in detail in different diagrams for both phase velocity and wave frequency. Also, accuracy of introduced model is verified comparing responses of present model with those of former papers.