Monte Carlo analysis of neck linker extension in kinesin molecular motors

Kinesin stepping is thought to involve both concerted conformational changes and diffusive movement, but the relative roles played by these two processes are not clear. The neck linker docking model is widely accepted in the field, but the remainder of the step--diffusion of the tethered head to the next binding site--is often assumed to occur rapidly with little mechanical resistance. Here, we investigate the effect of tethering by the neck linker on the diffusive movement of the kinesin head, and focus on the predicted behavior of motors with naturally or artificially extended neck linker domains. The kinesin chemomechanical cycle was modeled using a discrete-state Markov chain to describe chemical transitions. Brownian dynamics were used to model the tethered diffusion of the free head, incorporating resistive forces from the neck linker and a position-dependent microtubule binding rate. The Brownian dynamics and chemomechanical cycle were coupled to model processive runs consisting of many 8 nm steps. Three mechanical models of the neck linker were investigated: Constant Stiffness (a simple spring), Increasing Stiffness (analogous to a Worm-Like Chain), and Reflecting (negligible stiffness up to a limiting contour length). Motor velocities and run lengths from simulated paths were compared to experimental results from Kinesin-1 and a mutant containing an extended neck linker domain. When tethered by an increasingly stiff spring, the head is predicted to spend an unrealistically short amount of time within the binding zone, and extending the neck is predicted to increase both the velocity and processivity, contrary to experiments. These results suggest that the Worm-Like Chain is not an adequate model for the flexible neck linker domain. The model can be reconciled with experimental data if the neck linker is either much more compliant or much stiffer than generally assumed, or if weak kinesin-microtubule interactions stabilize the diffusing head near its binding site.     

Analysis of opening shock of a chest mounted reserve parachute

The effect of opening shock of a chest-mounted reserve parachute on the head/neck dynamics is studied. Comparisons are made with similar effects of a back-mounted reserve parachute. The analysis employs a biodynamic computer model developed in earlier research. The results show that there are significant advantages of a chest-mounted over a back-mounted reserve parachute.     

A three-dimensional model of the human cervical spine for impact simulation

A three-dimensional analytical model of the cervical spine is described. The cervical vertebrae and the head are modeled as rigid bodies which are interconnected by deformable elements representing the intervertebral disks, facet joints, ligaments and muscles. A special pentahedral continuum element for representing the articular facets is described which effectively maintains stability of the cervical spine in both lateral and frontal plane accelerations, which is very difficult with multi-spring models of the facets. A simplified representation is used for the spine and body below the level of T1. The neck musculature is modeled by over 100 muscle elements representing 22 major muscle groups in the neck. The model has been validated for frontal and sideways impact accelerations by simulating published experimental data. Results are also presented to show the effects of the stretch reflex response on the dynamics of the head and neck under moderate acceleration.     

Computational biomechanics of human brain with and without the inclusion of the body under different blast orientation

Three different human head models in a free space are exposed to blast waves coming from four different directions. The four head–neck–body models composed of model a, with the neck free in space; model b, with neck fixed at the bottom; and model c, with the neck attached to the body. The results show that the effect of the body can be ignored for the first milliseconds of the head–blast wave interactions. Also one can see that although most biomechanical responses of the brain have similar patterns in all models, the shear stresses are heavily increased after a few milliseconds in model b in which the head motion is obstructed by the fixed-neck boundary conditions. The free-floating head model results are closer to the attached-body model.     

An Interatomic Potential Model for H2O: Applications to Water and Ice Polymorphs

Abstract

A new interatomic potential model for H₂O which consists of 2-body central (O-H, O-O and H-H) and 3-body teams and does not contain artificial constraints on the motions of oxygen and hydrogen atoms is proposed. The interatomic potential function parameters were determined empirically so as to reproduce the fundamental and essential features of water and ice Ih using molecular dynamics (MD) methods.

We carried out the MD simulations of water, and find the Ice Ih, Ice II and Ice IX using this potential model, in structures and physical properties are in agreement with the experimental results except for the compressibilities of both water and ice Ih. We expect that, by refining this model, we can apply this model to problems involving the reaction of water molecules with other components.     

A biomechanical evaluation of whiplash using a multi-body dynamic model

This paper presents a biomechanical evaluation of whiplash injury potential during the initial extension motion of the head in a rear-end collision. A four-segment dynamic model is developed in the sagittal plane for the analysis. The model response is validated using the existing experimental data and is shown to simulate the "S-shape" kinematics of the cervical spine and the resulting dynamics observed in human and cadaver experiments. The model is then used to evaluate the effects of parameters such as collision severity, head/headrest separation, and the initial head orientation in the sagittal plane on the "S-shape" kinematics of the cervical spine and the resulting neck loads. It is shown, for example, that the cervical spine forms an "S-shape" for a range of change in speeds and that at lower and higher speeds changes the spine does not form the "S-shape." Furthermore, it is shown that the "S-shape" formation also depends on the head to headrest separation distance.     

A single ThinPrep® slide may not be representative in all head and neck fine needle aspirate specimens

Objectives:  Ideally, head and neck aspiration should be performed by trained aspirators within the setting of a one-stop clinic, where smeared material is available for immediate assessment. However, this may not always be possible for practical reasons and the use of liquid-based techniques in head and neck cytology is increasing. Although liquid-based cytology has been extensively validated for use in gynaecological cytology, no studies have investigated whether or not a single ThinPrep ^® slide is representative for head and neck aspirate specimens. We performed a prospective audit of head and neck fine needle aspiration specimens processed by the ThinPrep ^® method to investigate whether a single ThinPrep ^® slide was representative.
Methods:  A prospective audit of 115 consecutive head and neck aspirates was carried out. A single ThinPrep ^® slide was prepared and a diagnosis recorded. The remainder of the specimen was then spun down and prepared as a cell block. The ThinPrep ^® and cell block diagnoses were compared.
Results:  In 36 cases (31%), the cell block provided additional information that contributed to the diagnosis. In 14 (12%), the cell block was regarded as essential to the diagnosis.
Conclusions:  A single ThinPrep^® slide may not provide representative diagnostic material in all head and neck aspirates. This should be taken into consideration when contemplating the use of liquid-based methods for non-gynaecological cytology.     

Kinesin's biased stepping mechanism: amplification of neck linker zippering

A physically motivated model of kinesin's motor function is developed within the framework of rectified Brownian motion. The model explains how the amplification of neck linker zippering arises naturally through well-known formulae for overdamped dynamics, thereby providing a means to understand how weakly-favorable zippering leads to strongly favorable plus-directed binding of a free kinesin head to microtubule. Additional aspects of kinesin's motion, such as head coordination and rate-limiting steps, are directly related to the force-dependent inhibition of ATP binding to a microtubule bound head. The model of rectified Brownian motion is presented as an alternative to power stroke models and provides an alternative interpretation for the significance of ATP hydrolysis in the kinesin stepping cycle.     

Tooth Loss and Risk of Head and Neck Cancer: A Meta-Analysis

Background

Observational studies suggest an association between tooth loss and risk of head and neck cancer. However, whether tooth loss is an independent risk factor for head and neck cancer still remains controversial. The aim of this study is to assess the association between tooth loss and head and neck cancer risk.

Methods

Eligible studies were searched in PubMed and Embase databases from their inception to March 2013. A random-effects model or fixed-effects model was used to calculate the overall combined risk estimates.

Results

Eight case-control studies and one cross-sectional study involving 5,204 patients and 5,518 controls were included in the meta-analysis. The overall combined odds ratio for tooth loss and head and neck cancer was 2.00 (95% confidence interval, 1.28–3.14). Similar results yielded both in the moderate and severe tooth loss group. Sensitivity analysis based on various exclusion criteria maintained this significance with respect to head and neck cancer individually. Little evidence of publication bias was observed.

Conclusion

This meta-analysis suggests that tooth loss is associated with increased risk of head and neck cancer. This increase is probably independent of conventional head and neck cancer risk factors.     

Biodynamics model for operator head injury in stand-up lift trucks

Biodynamics and injury potential of operators in stand-up rider lift truck accidents have been investigated with a special focus on head injury. An anthropomorphic test device (ATD) model was used as an operator surrogate in computer simulations of off-the-dock (OTD) and tip-over (TO) accidents. The biomechanical model representing the ATD was developed based on rigid body segments, and then combined with a rigid body truck model in the accident simulations. The operator compartment of the truck model was enclosed with a rear door. The computed kinematics are in agreement with the results of previous experimental testing. A 2D finite element model of the head was created to compute head impact decelerations in the sagittal plane. Values of the head injury criterion for the TO cases were computed from the model and shown to compare favourably with experimental values. The results advance the state of knowledge concerning injury potential in TO and OTD accidents and simulation models for such accidents.     

Interactions among genetic variants in tobacco metabolizing genes and smoking are associated with head and neck cancer susceptibility in North Indians

It is becoming clearly evident that single gene or single environmental factor cannot explain susceptibility to diseases with complex etiology such as head and neck cancer. In this study, we applied the multifactor dimensionality reduction method to explore potential gene-environment and gene-gene interactions that may contribute to predisposition to head and neck cancer in the North Indian population. We genotyped 203 patients with head and neck cancer and 201 healthy controls for 13 functional polymorphisms in genes coding for tobacco metabolizing enzymes; CYP1A1, CYP2A13, GSTM1, and UGT1A7 using polymerase chain reaction-restriction fragment length polymorphism method, real-time polymerase chain reaction quantitative assay, and denaturing high-performance liquid chromatography followed by direct sequencing. We found that GSTM1 copy number variations were the most influential factor for head and neck cancer. We also observed significant gene-gene interactions among GSTM1 copy number variants, CYP1A1 T3801C and UGT1A7 T622C variants among smokers. Multifactor dimensionality reduction approach showed that the three-factor model, including smoking status, CYP1A1 T3801C, and GSTM1 copy number variants, conferred more than fourfold increased risk of head and neck cancer (odds ratio 4.89; 95% confidence interval: 3.15-7.32, p?相似文献   

Biodynamics model for operator head injury in stand-up lift trucks

Biodynamics and injury potential of operators in stand-up rider lift truck accidents have been investigated with a special focus on head injury. An anthropomorphic test device (ATD) model was used as an operator surrogate in computer simulations of off-the-dock (OTD) and tip-over (TO) accidents. The biomechanical model representing the ATD was developed based on rigid body segments, and then combined with a rigid body truck model in the accident simulations. The operator compartment of the truck model was enclosed with a rear door. The computed kinematics are in agreement with the results of previous experimental testing. A 2D finite element model of the head was created to compute head impact decelerations in the sagittal plane. Values of the head injury criterion for the TO cases were computed from the model and shown to compare favourably with experimental values. The results advance the state of knowledge concerning injury potential in TO and OTD accidents and simulation models for such accidents.     

Simulation of the effects of different pilot helmets on neck loading during air combat

New generation pilot helmets with mounted devices enhance the capabilities of pilots substantially. However, the additional equipment increases the helmet weight and shifts its center of mass forward. Two helmets with different mass properties were modeled to simulate their effects on the pilot's neck. A musculoskeletal computer model was used, with the methods of inverse dynamics and static optimization, to compute the muscle activations and joint reaction forces for a given range of quasi-static postures at various accelerations experienced during air combat. Head postures which induce much higher loads on the cervical spine than encountered in a neutral position could be identified. The increased weight and the forward shift of the center of mass of a new generation helmet lead to higher muscle activations and higher joint reaction loads over a wide range of head and neck movements. The muscle activations required to balance the head and neck in extreme postures increased the compressive force at the T1-C7 level substantially, while in a neutral posture the muscle activations remained low. The lateral neck muscles can reach activations of 100% and cause compressive joint forces up to 1100N during extensive rotations and extensions at high 'vertical' accelerations (Gz). The calculated values have to be interpreted with care as the model has not been validated. Nevertheless, this systematic analysis could separate the effects of head posture, acceleration and helmet mass on neck loading. More reliable data about mass properties and muscle morphometry with a more detailed motion analysis would help to refine the existing model.     

A dynamical model for reflex activated head movements in the horizontal plane

 We present a controls systems model of horizontal-plane head movements during perturbations of the trunk, which for the first time interfaces a model of the human head with neural feedback controllers representing the vestibulocollic (VCR) and the cervicocollic (CCR) reflexes. This model is homeomorphic such that model structure and parameters are drawn directly from anthropomorphic, biomechanical and physiological studies. Using control theory we analyzed the system model in the time and frequency domains, simulating neck movement responses to input perturbations of the trunk. Without reflex control, the head and neck system produced a second-order underdamped response with a 5.2 dB resonant peak at 2.1 Hz. Adding the CCR component to the system dampened the response by approximately 7%. Adding the VCR component dampened head oscillations by 75%. The VCR also improved low-frequency compensation by increasing the gain and phase lag, creating a phase minimum at 0.1 Hz and a phase peak at 1.1 Hz. Combining all three components (mechanics, VCR and CCR) linearly in the head and neck system reduced the amplitude of the resonant peak to 1.1 dB and increased the resonant frequency to 2.9 Hz. The closed loop results closely fit human data, and explain quantitatively the characteristic phase peak often observed. Received: 15 April 1996 / Accepted in revised form: 1 July 1996     

The use of accident reconstruction for the analysis of traumatic brain injury due to head impacts arising from falls

Brain injury is the leading cause of death in those aged under 45 years in both Europe and the USA. The objective of this research is to reconstruct and analyse real world cases of accidental head injury, thereby providing accurate data, which can be used subsequently to develop clinical tolerance levels associated with particular traumatic injuries and brain lesions. This paper looks at using numerical modelling techniques, namely multibody body dynamics and finite element methods, to reconstruct two real-life accident cases arising from falls. Preliminary results show the levels of acceleration of the head and deformation of brain tissue correspond well to those found by other researchers, suggesting that this method is suitable for modeling head-injury accidents.     

The use of accident reconstruction for the analysis of traumatic brain injury due to head impacts arising from falls

Brain injury is the leading cause of death in those aged under 45 years in both Europe and the USA. The objective of this research is to reconstruct and analyse real world cases of accidental head injury, thereby providing accurate data, which can be used subsequently to develop clinical tolerance levels associated with particular traumatic injuries and brain lesions. This paper looks at using numerical modelling techniques, namely multibody body dynamics and finite element methods, to reconstruct two real-life accident cases arising from falls. Preliminary results show the levels of acceleration of the head and deformation of brain tissue correspond well to those found by other researchers, suggesting that this method is suitable for modeling head-injury accidents.     

Airflow behavior changes in upper airway caused by different head and neck positions: Comparison by computational fluid dynamics

The feasibility of computational fluid dynamics (CFD) to evaluate airflow characteristics in different head and neck positions has not been established. This study compared the changes in volume and airflow behavior of the upper airway by CFD simulation to predict the influence of anatomical and physiological airway changes due to different head–neck positions on mechanical ventilation. One awake volunteer with no risk of difficult airway underwent computed tomography in neutral position, extension position (both head and neck extended), and sniffing position (head extended and neck flexed). Three-dimensional airway models of the upper airway were reconstructed. The total volume (V) and narrowest area (A_min) of the airway models were measured. CFD simulation with an Spalart–Allmaras model was performed to characterize airflow behavior in neutral, extension, and sniffing positions of closed-mouth and open-mouth ventilation. The comparison result for V was neutral <extension≈sniffing, and for A_min was neutral<extension<sniffing. A_min in sniffing position was nearly 3.0 times that in neutral position and 1.7 times that in extension position. The pressure drop and velocity increasing were more obvious in neutral than sniffing or extension position at the same airflow rate. In sniffing position, pressure differences decreased and velocity remained almost constant. Recirculation airflow was generated near the subglottic region in neutral and extension positions. Sniffing position improves airway patency by increasing airway volume and decreasing airway resistance, suggesting that sniffing position may be the optimal choice for mask ventilation.     

Dynamics of the head-neck complex in response to the trunk horizontal vibration: modeling and identification

Although many studies exist concerning the influence of seat vibration on the head in the seated human body, the dynamic response of the head-neck complex (HNC) to the trunk vibration has not been well investigated. Little quantitative knowledge exists about viscoelastic parameters of the neck. In this study, the dynamics of the HNC is identified when it is exposed to the trunk horizontal (fore-and-aft) vibration. The frequency response functions between the HNC angular velocity and the trunk horizontal acceleration, corresponding to four volunteers, are obtained in the frequency range of 0.5 Hz to 10 Hz. A fourth-order mathematical model, derived by considering a double-inverted-pendulum model for the HNC, is designed to simulate the dynamic response of the HNC to the trunk horizontal vibration. The frequency domain identification method is used to determine the coefficients of the mathematical model of the HNC. Good agreement has been obtained between experimental and simulation results. This indicates that the system, similar to the designed fourth-order model, has mainly two resonance frequencies. The viscoelastic parameters of the neck, including the spring and damping coefficients, are then obtained by use of the optimization method.     

Development and validation of a human biomechanical model for rib fracture and thorax injuries in blunt impact

From 1990 to approximately 50,000–120,000 people die annually of road traffic accidents in China. Traffic accidents are the main cause of death of Chinese adults aged 15–45 years. This study aimed to determine the biomechanical response and injury tolerance of the human body in traffic accidents. The subject was a 35-year-old male with a height of 170 cm, weight of 70 kg and Chinese characteristics at the 50th percentile. Geometry was generated by computed tomography and magnetic resonance imaging. A human-body biomechanical model was then developed. The model featured in great detail the main anatomical characteristics of skeletal tissues, soft tissues and internal organs, including the head, neck, shoulder, thoracic cage, abdomen, spine, pelvis, pleurae and lungs, heart, aorta, arms, legs, and other muscle tissues and skeletons. The material properties of all tissues in the human body model were obtained from the literature. Material properties were developed in the LS-DYNA code to simulate the mechanical behaviour of the biological tissues in the human body. The model was validated against cadaver responses to frontal and side impact. The predicted model response reasonably agreed with the experimental data, and the model can further be used to evaluate thoracic injury in real-world crashes. We believe that the transportation industry can use numerical models in the future to simultaneously reduce physical testing and improve automotive safety.     

Analysis of the BadA stalk from Bartonella henselae reveals domain-specific and domain-overlapping functions in the host cell infection process

Human pathogenic Bartonella henselae cause cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of B. henselae is the trimeric autotransporter adhesin Bartonella adhesin A (BadA) which is modularly constructed and consists of a head, a long and repetitive neck‐stalk module with 22 repetitive neck/stalk repeats and a membrane anchor. The BadA head is crucial for bacterial adherence to host cells, binding to several extracellular matrix proteins and for the induction of vascular endothelial growth factor (VEGF) secretion. Here, we analysed the biological role of the BadA stalk in the infection process in greater detail. For this purpose, BadA head‐bearing and headless deletion mutants with different lengths (containing one or four neck/stalk repeats in the neck‐stalk module) were produced and functionally analysed for their ability to bind to fibronectin, collagen and endothelial cells and to induce VEGF secretion. Whereas a head‐bearing short version (one neck/stalk element) of BadA lacks exclusively fibronectin binding, a substantially truncated headless BadA mutant was deficient for all of these biological functions. The expression of a longer headless BadA mutant (four neck/stalk repeats) restored fibronectin and collagen binding, adherence to host cells and the induction of VEGF secretion. Our data suggest that (i) the stalk of BadA is exclusively responsible for fibronectin binding and that (ii) both the head and stalk of BadA mediate adherence to collagen and host cells and the induction of VEGF secretion. This indicates overlapping functions of the BadA head and stalk.