A computational neural model that incorporates both intrinsic dynamics and sensory feedback in the Aplysia feeding network.

Studying the nervous system underlying animal motor control can shed light on how animals can adapt flexibly to a changing environment. We focus on the neural basis of feeding control in Aplysia californica. Using the Synthetic Nervous System framework, we developed a model of Aplysia feeding neural circuitry that balances neurophysiological plausibility and computational complexity. The circuitry includes neurons, synapses, and feedback pathways identified in existing literature. We organized the neurons into three layers and five subnetworks according to their functional roles. Simulation results demonstrate that the circuitry model can capture the intrinsic dynamics at neuronal and network levels. When combined with a simplified peripheral biomechanical model, it is sufficient to mediate three animal-like feeding behaviors (biting, swallowing, and rejection). The kinematic, dynamic, and neural responses of the model also share similar features with animal data. These results emphasize the functional roles of sensory feedback during feeding.

Scaling of buccal mass growth and muscle activation determine the duration of feeding behaviours in the marine mollusc Aplysia californica.

The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviours, which may both be affected by size-dependent scaling. The mechanics of slow movements in small animals are dominated by elastic forces and are thus quasistatic (i.e. always near mechanical equilibrium). Muscular forces producing movement and elastic forces resisting movement should scale identically (proportional to mass2/3), leaving the scaling of the time constant of muscle activation to play a critical role in determining behavioural duration. We tested this hypothesis by measuring the duration of feeding behaviours in the marine mollusc Aplysia californica whose body sizes spanned three orders of magnitude. The duration of muscle activation was determined by measuring the time it took for muscles to produce maximum force as A. californica attempted to feed on tethered inedible seaweed, which provided an in vivo approximation of an isometric contraction. The timing of muscle activation scaled with mass0.3. The total duration of biting behaviours scaled identically, with mass0.3, indicating a lack of additional mechanical effects. The duration of swallowing behaviour, however, exhibited a shallower scaling of mass0.17. We suggest that this was due to the allometric growth of the anterior retractor muscle during development, as measured by micro-computed tomography (micro-CT) scans of buccal masses. Consequently, larger A. californica did not need to activate their muscles as fully to produce equivalent forces. These results indicate that muscle activation may be an important determinant of the scaling of behavioural durations in quasistatic systems.

Control of high-speed jumps in muscle and spring actuated systems: a comparative study of take-off energetics in bush-crickets (Mecopoda elongata) and locusts (Schistocerca gregaria).

The Orthoptera are a diverse insect order well known for their locomotive capabilities. To jump, the bush-cricket uses a muscle actuated (MA) system in which leg extension is actuated by contraction of the femoral muscles of the hind legs. In comparison, the locust uses a latch mediated spring actuated (LaMSA) system, in which leg extension is actuated by the recoil of spring-like structure in the femur. The aim of this study was to describe the jumping kinematics of Mecopoda elongata (Tettigoniidae) and compare this to existing data in Schistocerca gregaria (Acrididae), to determine differences in control of rotation during take-off between similarly sized MA and LaMSA jumpers. 269 jumps from 67 individuals of M. elongata with masses from 0.014 g to 3.01 g were recorded with a high-speed camera setup. In M. elongata, linear velocity increased with mass0.18 and the angular velocity (pitch) decreased with mass-0.13. In S. gregaria, linear velocity is constant and angular velocity decreases with mass-0.24. Despite these differences in velocity scaling, the ratio of translational kinetic energy to rotational kinetic energy was similar for both species. On average, the energy distribution of M. elongata was distributed 98.8% to translational kinetic energy and 1.2% to rotational kinetic energy, whilst in S. gregaria it is 98.7% and 1.3%, respectively. This energy distribution was independent of size for both species. Despite having two different jump actuation mechanisms, the ratio of translational and rotational kinetic energy formed during take-off is fixed across these distantly related orthopterans.

Control of high-speed jumps: the rotation and energetics of the locust (Schistocerca gregaria).

Locusts (Schistocerca gregaria) jump using a latch mediated spring actuated system in the femur-tibia joint of their metathoracic legs. These jumps are exceptionally fast and display angular rotation immediately after take-off. In this study, we focus on the angular velocity, at take-off, of locusts ranging between 0.049 and 1.50 g to determine if and how rotation-rate scales with size. From 263 jumps recorded from 44 individuals, we found that angular velocity scales with mass-0.33, consistent with a hypothesis of locusts having a constant rotational kinetic energy density. Within the data from each locust, angular velocity increased proportionally with linear velocity, suggesting the two cannot be independently controlled and thus a fixed energy budget is formed at take-off. On average, the energy budget of a jump is distributed 98.7% to translational kinetic energy and gravitational potential energy, and 1.3% to rotational kinetic energy. The percentage of energy devoted to rotation was constant across all sizes of locusts and represents a very small proportion of the energy budget. This analysis suggests that smaller locusts find it harder to jump without body rotation.

Dual spring force couples yield multifunctionality and ultrafast, precision rotation in tiny biomechanical systems.

Small organisms use propulsive springs rather than muscles to repeatedly actuate high acceleration movements, even when constrained to tiny displacements and limited by inertial forces. Through integration of a large kinematic dataset, measurements of elastic recoil, energetic math modeling and dynamic math modeling, we tested how trap-jaw ants (Odontomachus brunneus) utilize multiple elastic structures to develop ultrafast and precise mandible rotations at small scales. We found that O. brunneus develops torque on each mandible using an intriguing configuration of two springs: their elastic head capsule recoils to push and the recoiling muscle-apodeme unit tugs on each mandible. Mandibles achieved precise, planar, circular trajectories up to 49,100 rad s-1 (470,000 rpm) when powered by spring propulsion. Once spring propulsion ended, the mandibles moved with unconstrained and oscillatory rotation. We term this mechanism a 'dual spring force couple', meaning that two springs deliver energy at two locations to develop torque. Dynamic modeling revealed that dual spring force couples reduce the need for joint constraints and thereby reduce dissipative joint losses, which is essential to the repeated use of ultrafast, small systems. Dual spring force couples enable multifunctionality: trap-jaw ants use the same mechanical system to produce ultrafast, planar strikes driven by propulsive springs and for generating slow, multi-degrees of freedom mandible manipulations using muscles, rather than springs, to directly actuate the movement. Dual spring force couples are found in other systems and are likely widespread in biology. These principles can be incorporated into microrobotics to improve multifunctionality, precision and longevity of ultrafast systems.

Medium compensation in a spring-actuated system.

Mantis shrimp strikes are one of the fastest animal movements, despite their occurrence in a water medium with viscous drag. Since the strike is produced by a latch-mediated spring-actuated system and not directly driven by muscle action, we predicted that strikes performed in air would be faster than underwater as a result of reduction in the medium's drag. Using high-speed video analysis of stereotyped strikes elicited from Squilla mantis, we found the exact opposite: strikes are much slower and less powerful in air than in water. S. mantis strikes in air have a similar mass and performance to latch-mediated spring-actuated jumps in locusts, suggesting a potential threshold for the energetics of a 1-2 g limb rotating in air. Drag forces induced by the media may be a key feature in the evolution of mantis shrimp strikes and provide a potential target for probing the braking system of these extremely fast movements.

The effect of size-scale on the kinematics of elastic energy release.

Elastically-driven motion has been used as a strategy to achieve high speeds in small organisms and engineered micro-robotic devices. We examine the size-scaling relations determining the limit of elastic energy release from elastomer bands that efficiently cycle mechanical energy with minimal loss. The maximum center-of-mass velocity of the elastomer bands was found to be size-scale independent, while smaller bands demonstrated larger accelerations and shorter durations of elastic energy release. Scaling relationships determined from these measurements are consistent with the performance of small organisms and engineered devices which utilize elastic elements to power motion.

Why do Large Animals Never Actuate Their Jumps with Latch-Mediated Springs? Because They can Jump Higher Without Them.

As animals get smaller, their ability to generate usable work from muscle contraction is decreased by the muscle's force-velocity properties, thereby reducing their effective jump height. Very small animals use a spring-actuated system, which prevents velocity effects from reducing available energy. Since force-velocity properties reduce the usable work in even larger animals, why don't larger animals use spring-actuated jumping systems as well? We will show that muscle length-tension properties limit spring-actuated systems to generating a maximum one-third of the possible work that a muscle could produce-greatly restricting the jumping height of spring-actuated jumpers. Thus a spring-actuated jumping animal has a jumping height that is one-third of the maximum possible jump height achievable were 100% of the possible muscle work available. Larger animals, which could theoretically use all of the available muscle energy, have a maximum jumping height that asymptotically approaches a value that is about three times higher than that of spring-actuated jumpers. Furthermore, a size related "crossover point" is evident for these two jumping mechanisms: animals smaller than this point can jump higher with a spring-actuated mechanism, while animals larger than this point can jump higher with a muscle-actuated mechanism. We demonstrate how this limit on energy storage is a consequence of the interaction between length-tension properties of muscles and spring stiffness. We indicate where this crossover point occurs based on modeling and then use jumping data from the literature to validate that larger jumping animals generate greater jump heights with muscle-actuated systems than spring-actuated systems.

The principles of cascading power limits in small, fast biological and engineered systems.

Mechanical power limitations emerge from the physical trade-off between force and velocity. Many biological systems incorporate power-enhancing mechanisms enabling extraordinary accelerations at small sizes. We establish how power enhancement emerges through the dynamic coupling of motors, springs, and latches and reveal how each displays its own force-velocity behavior. We mathematically demonstrate a tunable performance space for spring-actuated movement that is applicable to biological and synthetic systems. Incorporating nonideal spring behavior and parameterizing latch dynamics allows the identification of critical transitions in mass and trade-offs in spring scaling, both of which offer explanations for long-observed scaling patterns in biological systems. This analysis defines the cascading challenges of power enhancement, explores their emergent effects in biological and engineered systems, and charts a pathway for higher-level analysis and synthesis of power-amplified systems.

Jumping without slipping: leafhoppers (Hemiptera: Cicadellidae) possess special tarsal structures for jumping from smooth surfaces.

Many hemipteran bugs can jump explosively from plant substrates, which can be very smooth. We therefore analysed the jumping performance of froghoppers (Philaenus spumarius, Aphrophoridae) and leafhoppers (Aphrodes bicinctus/makarovi, Cicadellidae) taking off from smooth (glass) and rough (sandpaper, 30 µm asperity size) surfaces. On glass, the propulsive hind legs of Philaenus froghoppers slipped, resulting in uncontrolled jumps with a fast forward spin, a steeper angle and only a quarter of the velocity compared with jumps from rough surfaces. By contrast, Aphrodes leafhoppers took off without their propulsive hind legs slipping, and reached low take-off angles and high velocities on both substrates. This difference in jumping ability from smooth surfaces can be explained not only by the lower acceleration of the long-legged leafhoppers, but also by the presence of 2-9 soft pad-like structures (platellae) on their hind tarsi, which are absent in froghoppers. High-speed videos of jumping showed that platellae contact the surface briefly (approx. 3 ms) during the acceleration phase. Friction force measurements on individual hind tarsi on glass revealed that at low sliding speeds, both pushing and pulling forces were small, and insufficient to explain the recorded jumps. Only when the tarsi were pushed with higher velocities did the contact area of the platellae increase markedly, and high friction forces were produced, consistent with the observed jumps. Our findings show that leafhoppers have special adhesive footpads for jumping from smooth surfaces, which achieve firm grip and rapid control of attachment/detachment by combining anisotropic friction with velocity dependence.

Mechanosensory hairs in bumblebees (Bombus terrestris) detect weak electric fields.

Bumblebees (Bombus terrestris) use information from surrounding electric fields to make foraging decisions. Electroreception in air, a nonconductive medium, is a recently discovered sensory capacity of insects, yet the sensory mechanisms remain elusive. Here, we investigate two putative electric field sensors: antennae and mechanosensory hairs. Examining their mechanical and neural response, we show that electric fields cause deflections in both antennae and hairs. Hairs respond with a greater median velocity, displacement, and angular displacement than antennae. Extracellular recordings from the antennae do not show any electrophysiological correlates to these mechanical deflections. In contrast, hair deflections in response to an electric field elicited neural activity. Mechanical deflections of both hairs and antennae increase with the electric charge carried by the bumblebee. From this evidence, we conclude that sensory hairs are a site of electroreception in the bumblebee.

Increased muscular volume and cuticular specialisations enhance jump velocity in solitarious compared with gregarious desert locusts, Schistocerca gregaria.

The desert locust, Schistocerca gregaria, shows a strong phenotypic plasticity. It can develop, depending upon population density, into either a solitarious or gregarious phase that differs in many aspects of behaviour, physiology and morphology. Prominent amongst these differences is that solitarious locusts have proportionately longer hind femora than gregarious locusts. The hind femora contain the muscles and energy-storing cuticular structures that propel powerful jumps using a catapult-like mechanism. We show that solitarious locusts jump on average 23% faster and 27% further than gregarious locusts, and attribute this improved performance to three sources: first, a 17.5% increase in the relative volume of their hind femur, and hence muscle volume; second, a 24.3% decrease in the stiffness of the energy-storing semi-lunar processes of the distal femur; and third, a 4.5% decrease in the stiffness of the tendon of the extensor tibiae muscle. These differences mean that solitarious locusts can generate more power and store more energy in preparation for a jump than can gregarious locusts. This improved performance comes at a cost: solitarious locusts expend nearly twice the energy of gregarious locusts during a single jump and the muscular co-contraction that energises the cuticular springs takes twice as long. There is thus a trade-off between achieving maximum jump velocity in the solitarious phase against the ability to engage jumping rapidly and repeatedly in the gregarious phase.

Mechanism for rapid passive-dynamic prey capture in a pitcher plant.

Plants use rapid movements to disperse seed, spores, or pollen and catch animal prey. Most rapid-release mechanisms only work once and, if repeatable, regaining the prerelease state is a slow and costly process. We present an encompassing mechanism for a rapid, repeatable, passive-dynamic motion used by a carnivorous pitcher plant to catch prey. Nepenthes gracilis uses the impact of rain drops to catapult insects from the underside of the canopy-like pitcher lid into the fluid-filled trap below. High-speed video and laser vibrometry revealed that the lid acts as a torsional spring system, driven by rain drops. During the initial downstroke, the tip of the lid reached peak velocities similar to fast animal motions and an order of magnitude faster than the snap traps of Venus flytraps and catapulting tentacles of the sundew Drosera glanduligera. In contrast to these active movements, the N. gracilis lid oscillation requires neither mechanical preloading nor metabolic energy, and its repeatability is only limited by the intensity and duration of rainfall. The underside of the lid is coated with friction-reducing wax crystals, making insects more vulnerable to perturbations. We show that the trapping success of N. gracilis relies on the combination of material stiffness adapted for momentum transfer and the antiadhesive properties of the wax crystal surface. The impact-driven oscillation of the N. gracilis lid represents a new kind of rapid plant movement with adaptive function. Our findings establish the existence of a continuum between active and passive trapping mechanisms in carnivorous plants.

Hand-Assisted Robotic Surgery for Staging of Ovarian Cancer and Uterine Cancers With High Risk of Peritoneal Spread: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to determine surgical outcomes related to hand-assisted robotic surgery (HARS) for staging of ovarian cancer and uterine cancers with high risk of peritoneal spread and compare them to laparotomy and standard robotic-assisted surgery. METHODS: A retrospective cohort study of women undergoing staging for uterine and ovarian cancer between January 2011 and July 2013 at a major metropolitan teaching hospital was reviewed. Patients undergoing HARS were matched with patients undergoing staging laparotomy [exploratory laparotomy (XLAP)] for the same indications and with patients undergoing traditional robotic surgery (RS) for staging of endometrioid endometrial cancer. In HARS, a longer incision is used to allow palpation of the peritoneal surfaces, to exteriorize the small bowel, to examine the mesentery, and to perform omentectomy. RESULTS: One hundred five patients were analyzed (15 HARS, 45 RS, 45 XLAP). Compared with XLAP, HARS was associated with decreased blood loss (200 vs 400 mL, P = 0.011) and shorter hospital stay (1 vs 4 days, P < 0.001). Patients who had undergone HARS had fewer major complications, but those results did not reach statistical significance (0% vs 27%, P = 0.063). Hand-assisted robotic surgery was associated with higher blood loss and length of stay as compared to robotic staging of endometrioid endometrial cancer (RS). Minor wound complications were also more common (27% vs 2%, P = 0.012). CONCLUSIONS: Hand-assisted robotic surgery allows for thorough visual and tactile assessment of peritoneal surfaces. It represents a safe alternative to laparotomy for staging of ovarian and uterine cancers with high risk of peritoneal spread. Long-term follow-up study is needed to determine oncologic adequacy of HARS.

Mantises exchange angular momentum between three rotating body parts to jump precisely to targets.

Flightless animals have evolved diverse mechanisms to control their movements in air, whether falling with gravity or propelling against it. Many insects jump as a primary mode of locomotion and must therefore precisely control the large torques generated during takeoff. For example, to minimize spin (angular momentum of the body) at takeoff, plant-sucking bugs apply large equal and opposite torques from two propulsive legs [1]. Interacting gear wheels have evolved in some to give precise synchronization of these legs [2, 3]. Once airborne, as a result of either jumping or falling, further adjustments may be needed to control trajectory and orient the body for landing. Tails are used by geckos to control pitch [4, 5] and by Anolis lizards to alter direction [6, 7]. When falling, cats rotate their body [8], while aphids [9] and ants [10, 11] manipulate wind resistance against their legs and thorax. Falling is always downward, but targeted jumping must achieve many possible desired trajectories. We show that when making targeted jumps, juvenile wingless mantises first rotated their abdomen about the thorax to adjust the center of mass and thus regulate spin at takeoff. Once airborne, they then smoothly and sequentially transferred angular momentum in four stages between the jointed abdomen, the two raptorial front legs, and the two propulsive hind legs to produce a controlled jump with a precise landing. Experimentally impairing abdominal movements reduced the overall rotation so that the mantis either failed to grasp the target or crashed into it head first.

Animal biomechanics: a new silent partner in the control of motion.

A new kind of passive force has been discovered in the joints of insects, one that is a large contributor to almost every leg motion, from posture to scratching to locomotion.

Primary squamous cell carcinoma of the endometrium: two cases and a review of the literature.

Primary squamous cell carcinoma of the endometrium (PSCCE) is a rare entity, with fewer than 100 cases reported in the literature. We report two cases of PSCCE and review the literature regarding associated markers and treatment outcomes. Many different markers have been tested for association with PSCCE, with mixed results. Thus, it is likely that several etiologic factors are responsible for the development of PSCCE. Further, due to the rarity of the condition, the optimal postoperative management of patients with PSCCE remains to be defined.

A phase II evaluation of aflibercept in the treatment of recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study.

OBJECTIVES: Aflibercept targets vascular endothelial growth factor and placental growth factor. We evaluated activity and toxicity of aflibercept in recurrent/persistent endometrial cancer patients. Biomarkers and association with clinical characteristics and outcome were explored. METHODS: Eligible patients had measurable disease; 1-2 prior cytotoxic regimens; performance status 0-2. Aflibercept 4 mg/kg IV q14 days (28-day cycles) was administered until disease progression or prohibitive toxicity. Primary endpoints were the proportion of patients with progression-free survival at 6 months (PFS6) and tumor response rate. A flexible two-stage group sequential design to detect 20% increases in the proportion of patients responding or enduring PFS6 with 90% power (α=10%) was employed. RESULTS: Forty-nine patients were enrolled; five were excluded: wrong primary (2), second primary (1), wrong cell type (1); and never treated (1). Median age was 64 (range 48-83). Eighteen patients (41%) had two prior regimens; 27 (61%) had prior radiation. The PFS6 rate was 41%; three patients (7%, 90% CI: 2-17) had partial response. Of note, 10 patients (23%) met the PFS6 endpoint without starting a subsequent therapy; the remaining eight patients discontinued therapy for toxicity and started another therapy before 6 months elapsed. Median PFS and overall survival were 2.9 months and 14.6 months, respectively. Significant grade 3/4 toxicities were: cardiovascular (23%/5%), constitutional (7%/0), hemorrhage (2%/5%), metabolic (7%/2%), and pain (18%/0). Two treatment-related deaths were recorded: GI perforation (1), and arterial rupture (1). FGF1 expression was associated with response. CONCLUSIONS: Aflibercept met pretrial activity parameters, but was associated with significant toxicity at this dose and schedule in this population.

Locusts use a composite of resilin and hard cuticle as an energy store for jumping and kicking.

Locusts jump and kick by using a catapult mechanism in which energy is first stored and then rapidly released to extend the large hind legs. The power is produced by a slow contraction of large muscles in the hind femora that bend paired semi-lunar processes in the distal part of each femur and store half the energy needed for a kick. We now show that these energy storage devices are composites of hard cuticle and the rubber-like protein resilin. The inside surface of a semi-lunar process consists of a layer of resilin, particularly thick along an inwardly pointing ridge and tightly bonded to the external, black cuticle. From the outside, resilin is visible only as a distal and ventral triangular area that tapers proximally. High-speed imaging showed that the semi-lunar processes were bent in all three dimensions during the prolonged muscular contractions that precede a kick. To reproduce these bending movements, the extensor tibiae muscle was stimulated electrically in a pattern that mimicked the normal sequence of its fast motor spikes recorded in natural kicking. Externally visible resilin was compressed and wrinkled as a semi-lunar process was bent. It then sprung back to restore the semi-lunar process rapidly to its original natural shape. Each of the five nymphal stages jumped and kicked and had a similar distribution of resilin in their semi-lunar processes as adults; the resilin was shed with the cuticle at each moult. It is suggested that composite storage devices that combine the elastic properties of resilin with the stiffness of hard cuticle allow energy to be stored by bending hard cuticle over only a small distance and without fracturing. In this way all the stored energy is returned and the natural shape of the femur is restored rapidly so that a jump or kick can be repeated.