Analysis of the reflexive feedback control loop during posture maintenance

 In previous work it has been shown in posture experiments of the human arm that reflexive dynamics were substantial for narrow-band stochastic force disturbances. The estimated reflex gains varied substantially with the frequency content of the disturbances. The present study analyses a simplified linear model of the reflexive feedback control loop, to provide an explanation for the observed behaviour. The model describes co-activation and reflexive feedback. The task instruction `minimize the displacements' is represented mathematically by a cost function that is minimized by adjusting the parameters of the model. Small-amplitude displacements allow the system to be analysed with a quasi-linear approach. The optimization results clarify the limited effectiveness of reflexive feedback on the system's closed-loop behaviour, which emanates from the time delay present in the reflex loops. For low-frequency inputs less than 5 Hz, boundary-stable solutions with high reflex gains are predicted to be optimal. Input frequencies near the system's eigenfrequency (about 5 Hz), however, would be amplified and result in oscillatory behaviour. As long as the disturbance does not excite these frequencies, boundary stability will be optimal. The predicted reflex gains show a striking similarity with the estimated reflex gains from the experimental study. The present model analysis also provides a clear explanation for the negative reflex gains, estimated for near-sinusoidal inputs beyond 1.5 Hz. Received: 24 January 2000 / Accepted in revised form: 7 July 2000     

Orientation of tendons in vivo with active and passive knee muscles

Tendon orientations in knee models are often taken from cadaver studies. The aim of this study was to investigate the effect of muscle activation on tendon orientation in vivo. Magnetic resonance imaging (MRI) images of the knee were made during relaxation and isometric knee extensions and flexions with 0 degrees , 15 degrees and 30 degrees of knee joint flexion. For six tendons, the orientation angles in sagittal and frontal plane were calculated. In the sagittal plane, muscle activation pulled the patellar tendon to a more vertical orientation and the semitendinosus and sartorius tendons to a more posterior orientation. In the frontal plane, the semitendinosus had a less lateral orientation, the biceps femoris a more medial orientation and the patellar tendon less medial orientation in loaded compared to unloaded conditions. The knee joint angle also influenced the tendon orientations. In the sagittal plane, the patellar tendon had a more anterior orientation near full extension and the biceps femoris had an anterior orientation with 0 degrees and 15 degrees flexions and neutral with 30 degrees flexions. Within 0 degrees to 30 degrees of flexion, the biceps femoris cannot produce a posterior shear force and the anterior angle of the patellar tendon is always larger than the hamstring tendons. Therefore, co-contraction of the hamstring and quadriceps is unlikely to reduce anterior shear forces in knee angles up to 30 degrees . Finally, inter-individual variation in tendon angles was large. This suggests that the amount of shear force produced and the potential to counteract shear forces by co-contraction is subject-specific.     

The effect of control strategies for an active back-support exoskeleton on spine loading and kinematics during lifting

With mechanical loading as the main risk factor for LBP, exoskeletons (EXO) are designed to reduce the load on the back by taking over part of the moment normally generated by back muscles. The present study investigated the effect of an active exoskeleton, controlled using three different control modes (INCLINATION, EMG & HYBRID), on spinal compression forces during lifting with various techniques.Ten healthy male subjects lifted a 15 kg box, with three lifting techniques (free, squat & stoop), each of which was performed four times, once without EXO and once each with the three different control modes. Using inverse dynamics, we calculated L5/S1 joint moments. Subsequently, we estimated spine forces using an EMG-assisted trunk model.Peak compression forces substantially decreased by 17.8% when wearing the EXO compared to NO EXO. However, this reduction was partly, by about one third, attributable to a reduction of 25% in peak lifting speed when wearing the EXO. While subtle differences in back load patterns were seen between the three control modes, no differences in peak compression forces were found. In part, this may be related to limitations in the torque generating capacity of the EXO. Therefore, with the current limitations of the motors it was impossible to determine which of the control modes was best. Despite these limitations, the EXO still reduced both peak and cumulative compression forces by about 18%.     

Optimal control of antagonistic muscles

Recently, a model for a pair of antogonistic muscles has been studied (O?uztöreli and Stein, 1982). In the present paper we formulate and investigate the minimization of the costs associated with the time to complete the movement, the oscillation about the end-point, the energy costs to the muscles to complete the movement, the cost to the nervous system to supply the inputs, and the cost of reliability in the face of perturbing forces. To solve these optimization problems the maximum principle of Pontryagin is employed. In all of these optimization problems, except the energy optimal problem, the optimal controls (active states or nervous inputs) are of the bang-bang type.     

Novel control strategies for mosquito-borne diseases

Mosquito-borne diseases are an increasing global health challenge, threatening over 40% of the world''s population. Despite major advances in malaria control since 2000, recent progress has stalled. Additionally, the risk of Aedes-borne arboviruses is rapidly growing, with the unprecedented spread of dengue and chikungunya viruses, outbreaks of yellow fever and the 2015 epidemic of Zika virus in Latin America. To counteract this growing problem, diverse and innovative mosquito control technologies are currently under development. Conceptually, these span an impressive spectrum of approaches, from invasive transgene cassettes with the potential to crash mosquito populations or reduce the vectorial capacity of a population, to low-cost alterations in housing design that restrict mosquito entry. This themed issue will present articles providing insight into the breadth of mosquito control research, while demonstrating the requirement for an interdisciplinary approach. The issue will highlight mosquito control technologies at varying stages of development and includes both opinion pieces and research articles with laboratory and field-based data on control strategy development.This article is part of the theme issue ‘Novel control strategies for mosquito-borne diseases''.     

Mechanical models for insect locomotion: active muscles and energy losses

 We extend the analysis of simple, energy-conserving models for the dynamics of insect locomotion in the horizontal plane developed in Schmitt and Holmes (2000a,b, 2001), where gaits characteristic of steady cockroach running and turning were evoked. In this paper, we include dissipation and energy inputs via active “muscles” in three forms: via prescribed torques at the “hip” pivot, via an active spring element of variable length, and via a pair of Hill-type muscle models representing an extensor/flexor system. Due to mechanical feedback of passive elastic forces, the stable gaits of the conservative models are preserved, and now energy input and absorption balances to additionally stabilize a preferred speed, with only modest neural sensing and feedback being required. However, these bipedal models still cannot simultaneously match observed moment-yaw magnitudes and fore-aft dynamics. Received: 17 September 2001 / Accepted: 20 February 2003 / Published online: 20 May 2003 Correspondence to: P. Holmes (e-mail: pholmes@math.Princeton.EDU) Acknowledgements. This work was supported by DARPA/ONR: N00014-98-1-0747 and DoE: DE-FG02-95ER25238. John Schmitt was partially supported by a DoD Graduate Fellowship, a Wu Fellowship of the School of Engineering and Applied Science, and a George Van Ness Lothrop Honorific Fellowship of the Graduate School at Princeton University. We thank Kenneth Meijer for allowing us to use his muscle model in Sect. 4 and Bob Full and Dan Koditschek for numerous helpful suggestions.     

Folate-targeted immunotherapies: Passive and active strategies for cancer

The glycoprotein FRα is a membrane-attached transport protein that is shielded from the immune system in healthy cells. However, it is upregulated in various malignancies, involved in cancer development and is also immunogenic. Furthermore, FRα is a tumor-associated antigen endowed with unique properties, thus rendering it a suitable target for immunotherapeutic development in cancer. Various anti- FRα immunotherapeutic strategies are thus currently being developed and clinically assessed for the treatment of various solid tumors. These approaches include passive anti-FRα immunotherapies, such as monoclonal antibodies, or active immunotherapies, such as CART, folate haptens and vaccines. In this review, we will explore the advances in the field of FRα-based immune therapies and discuss both their successes and shortcomings in the clinical setting.     

Analysis of a model for antagonistic muscles

In the present work a linear model for a pair of antogonistic muscles is analysed. Each constituent muscle in this model is identical to ones considered previously (Stein and Ouztöreli, 1976). Analytical properties of the antagonistic muscles and dynamics of the system are described and some numerical results are discussed. The natural modes of the system are determined by a fourth order polynomial, which most commonly has one pair of conjugate complex roots and two negative real roots. The filtering of neural inputs through the active state properties of the muscle increases the order of the system to fifth order for these inputs.This work was partly supported by the National Scientific and Engineering Research Council of Canada Grant NRC-A4345 and by the Medical Research Council of Canada Grant MRC-MT-3307 through the University of Alberta     

Action of neck accessory muscles on rib cage in dogs

To investigate the action of the neck accessory muscles on the rib cage, we stimulated the sternocleidomastoid and the scalenus muscles separately in supine anesthetized dogs. Hooks screwed into the sternum and ribs were used to measure their axial displacements and the changes in anteroposterior (AP) and transverse (T) diameters of the rib cage. We found that the sternocleidomastoid and scalenus muscles, when they contract alone, cause a large axial displacement of the sternum and the ribs in a cephalad direction and expand the rib cage along both its AP and T diameters. Opening the abdomen increased the cephalad displacement of the ribs and the expansion of the lower rib cage, particularly along its T diameter, but reduced the increase in lung volume. These experiments indicate 1) that the action of the sternocleidomastoid and scalenus muscles on the rib cage is essentially the consequence of a rotation of the ribs' neck axes, resulting from the cephalad displacement of the ribs, and 2) that the fall in abdominal pressure, almost certainly by acting through the zone of apposition of the diaphragm to the rib cage, has a deflationary action on the lower rib cage, more markedly so on its lateral than its anterior wall. The experiments also suggest that the fall in abdominal pressure prevents the diaphragm from moving cephalad and aids the neck accessory muscles in inflating the lungs.     

Contractile characteristics and operating lengths of canine neck inspiratory muscles

The neck inspiratory muscles are recruited to support breathing under numerous conditions. To gain insight into their synergistic actions we examined the isometric contractile properties of bundles from canine scalene and sternomastoid muscles. In addition, we also related the length of the neck muscles, measured sonomicrometrically in vivo at different lung volumes and body positions, to their optimal force-producing length (Lo) determined in vitro. We found that the speed of the sternomastoid is somewhat faster than that of the scalene owing to a shorter relaxation rate; the sternomastoid generates higher forces at submaximal stimulation frequencies than the scalene; the maximal tetanic force corrected for cross-sectional area is the same for both neck muscles; the neck muscles are significantly faster than the canine costal diaphragm; at supine functional residual capacity (FRC), the scalene is operating at a length corresponding to 85% Lo, whereas the sternomastoid is significantly shorter at 75% Lo; increasing lung volume shortens both muscles slightly, the length at supine total lung capacity being approximately 5% shorter than at FRC; and in the upright posture, both neck muscles lengthen toward their Lo, with the sternomastoid lengthening more than the scalene. We conclude that the scalene is a more effective force generator than the sternomastoid with the animal lying supine; the neck muscles appear to maintain their force-generating potential regardless of the lung volume; and the force-generating potential of the neck muscles is greatly enhanced with the animal in the upright vs. the supine position. This may contribute to the augmented rib cage motion characteristic of breathing in the upright posture.     

Epidemiology in the strategies for malaria control

A rapid overview is presented of the evolution of the main orientations of malaria control, since the discovery of mosquito transmission. Stated control objectives appear to have oscillated between expectations to eradicate the vector, or at least the disease, and more modest approaches to minimise the effects of the infection. High optimism was raised when a new control measure, or new combination of existing measures, appeared to be highly effective and was expected to have universal applicability. The implementation of large scale campaigns eventually found the limits of applicability of the proposed strategy and the exaggerated expectations soon gave way to disillusion and, eventually, to a revival of research. The longest and most impacting period of exaggerated expectations was the global malaria eradication campaign of the 1950s and 1960s, which completely disregarded the study of local epidemiology, considering that all it was needed was to know if an area was "malarious" or not. Research was practically abandoned and, even when reinstated after the recognised failure of the campaign, it has retained an almost exclusive orientation towards the development of control tools, drugs or eventually vaccines. One of the earliest victims of the eradication campaign was the study of epidemic malaria and its determinants in different epidemic prone areas. In spite of an extremely long period of disillusion, lasting for almost two decades, the reality of the malaria problem led WHO and member countries to agree on a global strategy of control, aiming at a realistic use of existing tools, to at least reduce or prevent mortality. An essential element of this strategy is the prevention or control of malaria epidemics and the selective use of vector control, both of which have to be based on a solid knowledge of local epidemiology, the study of which has to rejoin the path abandoned fifty years ago.     

Practical genetic control strategies for industrial bioprocesses

Optimization of metabolism to maximize production of bio-based chemicals must consistently balance cellular resources for biocatalyst growth and desired compound synthesis. This mini-review discusses synthetic biology strategies for dynamically controlling expression of genes to enable dual-phase fermentations in which growth and production are separated into dedicated phases. Emphasis is placed on practical examples which can be reliably scaled to commercial production with the current state of technology. Recent case studies are presented, and recommendations are provided for environmental signals and genetic control circuits.     

Snail control strategies for reduction of schistosomiasis transmission

As intermediate hosts, molluscs play a major role in the transmission of schistosomes; they are the sites of an intense multiplication of parasites. Thus, snail control strategies are considered a priority for the reduction of schistosomiasis transmission. Here, Vinca Lardans and Colette Dissous review the efficacy of environmental management and the use of molluscicides and biological agents to control snail populations. They then describe the development of diagnostic tests, based on the detection of parasite antigens or specific parasite DNA sequences in snail tissues, to detect the early infection of snails. Finally, they discuss progress in studying the molecular basis of susceptibility and resistance phenotypes, and the possible application of the genetic manipulation of molluscs.     

Influences of neck vibration on lower limb extensor muscles in man

The effects of neck vibration were studied in ten healthy subjects standing in unrestrained or restrained conditions. An involuntary slow and gradual displacement of the body axis associated with a subjective experience of forward tilt occurred during vibration of the dorsal surface of the neck. This effect was associated with a decreased tonic contration of the antigravitary lower limb musculature. The amplitude of the H-reflex from the soleus muscle, recorded at progressively increasing time interval after the onset of the vibratory stimulus, showed complex interactions: in particular, in unrestrained conditions an early inhibitory phase occurred at about 100 msec, followed by a short-lasting facilitatory phase between 150-300 msec and by a late long-lasting excitatory component which started 500-600 msec after the onset of vibratory stimulus. In restrained subjects, the late excitatory phase disappeared and was substituted by a delayed depression. In this instance, the short-lasting facilitatory phase appeared to be superimposed on a background of inhibition. The effects produced by the neck input on the H-reflex were attenuated during vibration of the dorsal muscolature at L4-L5. The mechanisms involved in the cervical control of posture and reflex movements following neck vibration are discussed.