Jumping in lantern bugs (Hemiptera, Fulgoridae).

Lantern bugs are amongst the largest of the jumping hemipteran bugs, with body lengths reaching 44 mm and masses reaching 0.7 g. They are up to 600 times heavier than smaller hemipterans that jump powerfully using catapult mechanisms to store energy. Does a similar mechanism also propel jumping in these much larger insects? The jumping performance of two species of lantern bugs (Hemiptera, Auchenorrhyncha, family Fulgoridae) from India and Malaysia was therefore analysed from high-speed videos. The kinematics showed that jumps were propelled by rapid and synchronous movements of both hind legs, with their trochantera moving first. The hind legs were 20-40% longer than the front legs, which was attributable to longer tibiae. It took 5-6 ms to accelerate to take-off velocities reaching 4.65 m s-1 in the best jumps by female Kalidasa lanata. During these jumps, adults experienced an acceleration of 77 g, required an energy expenditure of 4800 µJ and a power output of 900 mW, and exerted a force of 400 mN. The required power output of the thoracic jumping muscles was 21,000 W kg-1, 40 times greater than the maximum active contractile limit of muscle. Such a jumping performance therefore required a power amplification mechanism with energy storage in advance of the movement, as in their smaller relatives. These large lantern bugs are near isometrically scaled-up versions of their smaller relatives, still achieve comparable, if not higher, take-off velocities, and outperform other large jumping insects such as grasshoppers.

Adhesive latching and legless leaping in small, worm-like insect larvae.

Jumping is often achieved using propulsive legs, yet legless leaping has evolved multiple times. We examined the kinematics, energetics and morphology of long-distance jumps produced by the legless larvae of gall midges (Asphondylia sp.). They store elastic energy by forming their body into a loop and pressurizing part of their body to form a transient 'leg'. They prevent movement during elastic loading by placing two regions covered with microstructures against each other, which likely serve as a newly described adhesive latch. Once the latch releases, the transient 'leg' launches the body into the air. Their average takeoff speeds (mean: 0.85 m s-1; range: 0.39-1.27 m s-1) and horizontal travel distances (up to 36 times body length or 121 mm) rival those of legged insect jumpers and their mass-specific power density (mean: 910 W kg-1; range: 150-2420 W kg-1) indicates the use of elastic energy storage to launch the jump. Based on the forces reported for other microscale adhesive structures, the adhesive latching surfaces are sufficient to oppose the loading forces prior to jumping. Energetic comparisons of insect larval crawling versus jumping indicate that these jumps are orders of magnitude more efficient than would be possible if the animals had crawled an equivalent distance. These discoveries integrate three vibrant areas in engineering and biology - soft robotics, small, high-acceleration systems, and adhesive systems - and point toward a rich, and as-yet untapped area of biological diversity of worm-like, small, legless jumpers.

Muscle-spring dynamics in time-limited, elastic movements.

Muscle contractions that load in-series springs with slow speed over a long duration do maximal work and store the most elastic energy. However, time constraints, such as those experienced during escape and predation behaviours, may prevent animals from achieving maximal force capacity from their muscles during spring-loading. Here, we ask whether animals that have limited time for elastic energy storage operate with springs that are tuned to submaximal force production. To answer this question, we used a dynamic model of a muscle-spring system undergoing a fixed-end contraction, with parameters from a time-limited spring-loader (bullfrog: Lithobates catesbeiana) and a non-time-limited spring-loader (grasshopper: Schistocerca gregaria). We found that when muscles have less time to contract, stored elastic energy is maximized with lower spring stiffness (quantified as spring constant). The spring stiffness measured in bullfrog tendons permitted less elastic energy storage than was predicted by a modelled, maximal muscle contraction. However, when muscle contractions were modelled using biologically relevant loading times for bullfrog jumps (50 ms), tendon stiffness actually maximized elastic energy storage. In contrast, grasshoppers, which are not time limited, exhibited spring stiffness that maximized elastic energy storage when modelled with a maximal muscle contraction. These findings demonstrate the significance of evolutionary variation in tendon and apodeme properties to realistic jumping contexts as well as the importance of considering the effect of muscle dynamics and behavioural constraints on energy storage in muscle-spring systems.

Take-off speed in jumping mantises depends on body size and a power-limited mechanism.

Many insects such as fleas, froghoppers and grasshoppers use a catapult mechanism to jump, and a direct consequence of this is that their take-off velocities are independent of their mass. In contrast, insects such as mantises, caddis flies and bush crickets propel their jumps by direct muscle contractions. What constrains the jumping performance of insects that use this second mechanism? To answer this question, the jumping performance of the mantis Stagmomantis theophila was measured through all its developmental stages, from 5 mg first instar nymphs to 1200 mg adults. Older and heavier mantises have longer hind and middle legs and higher take-off velocities than younger and lighter mantises. The length of the propulsive hind and middle legs scaled approximately isometrically with body mass (exponent=0.29 and 0.32, respectively). The front legs, which do not contribute to propulsion, scaled with an exponent of 0.37. Take-off velocity increased with increasing body mass (exponent=0.12). Time to accelerate increased and maximum acceleration decreased, but the measured power that a given mass of jumping muscle produced remained constant throughout all stages. Mathematical models were used to distinguish between three possible limitations to the scaling relationships: first, an energy-limited model (which explains catapult jumpers); second, a power-limited model; and third, an acceleration -: limited model. Only the model limited by muscle power explained the experimental data. Therefore, the two biomechanical mechanisms impose different limitations on jumping: those involving direct muscle contractions (mantises) are constrained by muscle power, whereas those involving catapult mechanisms are constrained by muscle energy.

Phase shift between joint rotation and actuation reflects dominant forces and predicts muscle activation patterns.

During behavior, the work done by actuators on the body can be resisted by the body's inertia, elastic forces, gravity, or viscosity. The dominant forces that resist actuation have major consequences on the control of that behavior. In the literature, features and actuation of locomotion, for example, have been successfully predicted by nondimensional numbers (e.g. Froude number and Reynolds number) that generally express the ratio between two of these forces (gravitational, inertial, elastic, and viscous). However, animals of different sizes or motions at different speeds may not share the same dominant forces within a behavior, making ratios of just two of these forces less useful. Thus, for a broad comparison of behavior across many orders of magnitude of limb length and cycle period, a dimensionless number that includes gravitational, inertial, elastic, and viscous forces is needed. This study proposes a nondimensional number that relates these four forces: the phase shift (ϕ) between the displacement of the limb and the actuator force that moves it. Using allometric scaling laws, ϕ for terrestrial walking is expressed as a function of the limb length and the cycle period at which the limb steps. Scale-dependent values of ϕ are used to explain and predict the electromyographic (EMG) patterns employed by different animals as they walk.

Spring and latch dynamics can act as control pathways in ultrafast systems.

Ultrafast movements propelled by springs and released by latches are thought limited to energetic adjustments prior to movement, and seemingly cannot adjust once movement begins. Even so, across the tree of life, ultrafast organisms navigate dynamic environments and generate a range of movements, suggesting unrecognized capabilities for control. We develop a framework of control pathways leveraging the non-linear dynamics of spring-propelled, latch-released systems. We analytically model spring dynamics and develop reduced-parameter models of latch dynamics to quantify how they can be tuned internally or through changing external environments. Using Lagrangian mechanics, we test feedforward and feedback control implementation via spring and latch dynamics. We establish through empirically-informed modeling that ultrafast movement can be controllably varied during latch release and spring propulsion. A deeper understanding of the interconnection between multiple control pathways, and the tunability of each control pathway, in ultrafast biomechanical systems presented here has the potential to expand the capabilities of synthetic ultra-fast systems and provides a new framework to understand the behaviors of fast organisms subject to perturbations and environmental non-idealities.

A buckling region in locust hindlegs contains resilin and absorbs energy when jumping or kicking goes wrong.

If a hindleg of a locust slips during jumping, or misses its target during kicking, energy generated by the two extensor tibiae muscles is no longer expended in raising the body or striking a target. How, then, is the energy in a jump (4100-4800 µJ) or kick (1700 µJ) dissipated? A specialised buckling region found in the proximal hind-tibia where the bending moment is high, but not present in the other legs, buckled and allowed the distal part of the tibia to extend. In jumps when a hindleg slipped, it bent by a mean of 23±14 deg at a velocity of 13.4±9.5 deg ms(-1); in kicks that failed to contact a target it bent by 32±16 deg at a velocity of 32.9±9.5 deg ms(-1). It also buckled 8.5±4.0 deg at a rate of 0.063±0.005 deg ms(-1) when the tibia was prevented from flexing fully about the femur in preparation for both these movements. By experimentally buckling this region through 40 deg at velocities of 0.001-0.65 deg ms(-1), we showed that one hindleg could store about 870 µJ on bending, of which 210 µJ was dissipated back to the leg on release. A band of blue fluorescence was revealed at the buckling region under UV illumination that had the two key signatures of the elastic protein resilin. A group of campaniform sensilla 300 µm proximal to the buckling region responded to imposed buckling movements. The features of the buckling region show that it can act as a shock absorber as proposed previously when jumping and kicking movements go wrong.

Biomechanics: Passive forces set the stage for stick insects.

For small animals like insects, passive elastic forces within their joints are extremely important to control of limb motion. A new study shows that these passive forces are tuned to the needs of individual joints.

Gravity and active acceleration limit the ability of killer flies (Coenosia attenuata) to steer towards prey when attacking from above.

Insects that predate aerially usually contrast prey against the sky and attack upwards. However, killer flies (Coenosia attenuata) can attack prey flying below them, performing what we term 'aerial dives'. During these dives, killer flies accelerate up to 36 m s-2. Although the trajectories of the killer fly's dives appear highly variable, proportional navigation explains them, as long as the model has the lateral acceleration limit of a real killer fly. The trajectory's steepness is explained by the initial geometry of engagement; steep attacks result from the killer fly taking off when the target is approaching the predator. Under such circumstances, the killer fly dives almost vertically towards the target, and gravity significantly increases its acceleration. Although killer flies usually time their take-off to minimize flight duration, during aerial dives killer flies cannot reach the lateral accelerations necessary to match the increase in speed caused by gravity. Since a close miss still leads the predator closer to the target, and might even slow the prey down, there may not be a selective pressure for killer flies to account for gravity during aerial dives.

The mechanics of azimuth control in jumping by froghopper insects.

Many animals move so fast that there is no time for sensory feedback to correct possible errors. The biomechanics of the limbs participating in such movements appear to be configured to simplify neural control. To test this general principle, we analysed how froghopper insects control the azimuth direction of their rapid jumps, using high speed video of the natural movements and modelling to understand the mechanics of the hind legs. We show that froghoppers control azimuth by altering the initial orientation of the hind tibiae; their mean angle relative to the midline closely predicts the take-off azimuth. This applies to jumps powered by both hind legs, or by one hind leg. Modelling suggests that moving the two hind legs at different times relative to each other could also control azimuth, but measurements of natural jumping showed that the movements of the hind legs were synchronised to within 32 mus of each other. The maximum timing difference observed (67 micros) would only allow control of azimuth over 0.4 deg. to either side of the midline. Increasing the timing differences between the hind legs is also energetically inefficient because it decreases the energy available and causes losses of energy to body spin; froghoppers with just one hind leg spin six times faster than intact ones. Take-off velocities also fall. The mechanism of azimuth control results from the mechanics of the hind legs and the resulting force vectors of their tibiae. This enables froghoppers to have a simple transform between initial body position and motion trajectory, therefore potentially simplifying neural control.

Insect jumping springs.

A quick guide to the springs used by insects to achieve remarkable feats of jumping.

Phase II trial of ifosfamide and mesna in advanced ovarian carcinoma: a Gynecologic Oncology Group Study.

Ifosfamide (isophosphamide) and mesna (2-mercaptoethane sodium sulfonate) were administered intravenously at monthly intervals to 46 patients with advanced epithelial ovarian carcinoma refractory to or recurrent after cisplatin-containing combination chemotherapy. Initially, ifosfamide was given as 1.5 g/m2/d x 5 days and mesna as 300 mg/m2 every 4 hours for three doses following ifosfamide, but the initial dose of ifosfamide was reduced to 1.2 g/m2 because of toxicity. Four of the patients initially entered were found to be ineligible: two who had had more than one prior chemotherapy regimen and two who did not have ovarian primaries. One patient received an inadequate trial and four patients had discontinuation of therapy because of toxicity, leaving 41 evaluable for response. Three patients (7.0%) had complete responses and five (13.0%) had partial responses for an overall response rate of 20.0%. Response duration ranged from 2.1 to 20.3 + months with a median of 6.9 + months. Two patients died of renal failure, one of whom had no known renal disease and received 1.5 g/m2/d x 5 days ifosfamide. The second patient received the 1.2 g/m2 dose and was found to have chronic pyelonephritis and pyonephrosis at autopsy. Gynecologic Oncology Group (GOG) grade 3 or 4 granulocytopenia was seen in eight (19.5%), grade 3 or 4 thrombocytopenia in four (9.8%), and grade 3 or 4 neurotoxicity in six (14.6%) of the 41 patients evaluable for toxicity. Ifosfamide/mesna is active in epithelial ovarian cancer. GOG trials in untreated patients are being initiated and toxicity is being evaluated.

Ten-year follow-up of patients receiving cisplatin, doxorubicin, and cyclophosphamide chemotherapy for advanced epithelial ovarian carcinoma.

Fifty-six patients were randomly assigned to receive either one-day cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy (PAC-I) or five-day PAC (PAC-V) for advanced epithelial ovarian carcinoma. Follow-up has been 120+ months or to death. Ninety-one percent had either suboptimal stage III or stage IV disease and 55% had grade 2 or 3 lesions. Two patients died of toxicity and were free of disease at autopsy. A third patient died of congestive heart failure with no disease at 103 months. Additionally, eight patients had a negative second-look laparotomy, and three (37.5%) are alive with no evidence of disease (NED) 133 to 144 months after diagnosis. Five patients (62.5%) died of disease 2 to 123 months after negative second-look. Patients with optimal stage III disease had a longer median progression-free interval (PFI) and survival (33.3 and 44.5 months, respectively) than those with suboptimal or stage IV disease (16.4 and 22.5 months, respectively), and the difference in median PFI is significant (P less than .02). Patients with ascites at diagnosis had a shorter median PFI and survival (14.7 and 18 months) than those without ascites (30.0 and 33.0 months). Both differences were significant (PFI, P less than .04; survival, P = .005). PAC produces response rates that are superior to those obtained historically with single-agent alkylating therapy. Late recurrences after negative second-look laparotomy suggest that 5-year survival data may be inadequate in ovarian carcinoma.

An intra-ovarian site for the luteolytic action of estrogen in the rhesus monkey.

To investigate whether estradiol can act within the ovary to induce luteolysis in the rhesus monkey, 100 mug estradiol-17beta were injected on one of days 2, 3, or 4 after the preovulatory LH peak into one of the following sites: the stroma of the ovary containing the developing corpus luteum, the stroma of the contralateral ovary, or sc. When estradiol was injected into the ovary containing the corpus luteum, the functional life span of the corpus luteum was shortened, reflected by a premature decline in circulating progesterone to levels characteristic of the follicular phase of the cycle and an early onset of menstruation. When estradiol was injected either sc or into the ovary contralateral to that containing the corpus luteum, the life span of the corpus luteum was not shortened. The differing responses could not be attributed to differing rates of efflux of estradiol from the various injection sites; patterns and levels of estradiol in peripheral serum were essentially the same regardless of injection site. Furthermore, the premature regression of the corpus luteum was not a consequence of surgical trauma associated with the intra-ovarian injection procedure, nor could it be mimicked by another ovarian hormone, progesterone. These findings lead to the conclusion that estrogens can induce functional luteolysis in the rhesus monkey by acting directly within the ovary containing the corpus luteum.

Secondary therapy for epithelial ovarian cancer--1994.

In women with recurrent epithelial ovarian cancer, secondary treatment options include surgery and chemotherapy. Surgery should be considered in patients with persistent disease at the time of second-look laparotomy and before chemotherapy in those whose disease recurs following long-term remission. With regard to secondary chemotherapy, active agents include cisplatin, carboplatin, ifosfamide, and paclitaxel. The effectiveness of hexamethylmelamine as salvage therapy is less clear, although it may be of use in patients who relapse soon after receiving primary platinum chemotherapy. Patients who receive platinum therapy initially and relapse after long periods of remission often respond to second-line platinum treatment. Ifosfamide may be effective in patients receiving one or two prior cisplatin-containing regimens, but is contraindicated in those with hepatic or renal insufficiency. Paclitaxel is the drug of choice for patients who have developed primary resistance to platinum therapy.

Phase II experience with ifosfamide/mesna in gynecologic malignancies: preliminary report of Gynecologic Oncology Group studies.

The Gynecologic Oncology Group initiated a series of phase II trials of ifosfamide/mesna in women with advanced or recurrent gynecologic malignancies in July 1985. Previously untreated patients received ifosfamide, 1.5 g/m2/d, intravenously (IV) for five days. Mesna was given IV in three doses every four hours after ifosfamide; each dose was 20% of the daily ifosfamide dose (ie, 300 mg/m2). All patients with ovarian and 87% of those with cervical cancer had undergone platinum-based therapy previously. Because of the toxicity encountered in previously treated ovarian cancer patients, the dose of ifosfamide was reduced to 1.2 g/m2/d in patients who had received prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (21.6%) of 37 evaluable patients with three (8.1%) complete responses. Response duration was 2.1 to 20.3+ months with a median of 6.9+ months. In squamous carcinoma of the cervix, three (11.1%) of 27 evaluable patients had partial responses of 1.8, 2.2, and 3.1 months' duration. Of 29 untreated patients with mixed mesodermal tumors of the uterus, five (17.9%) had complete and four (14.3%) had partial responses for an overall response rate of 32.2%. Response duration was 1.4+ to 8.6 months with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Gynecologic Oncology Group experience with ifosfamide.

In July 1985, the Gynecologic Oncology Group initiated a series of phase II trials with ifosfamide/mesna in advanced or recurrent gynecologic malignancies. Previously untreated patients received ifosfamide 1.5 g/m2/d intravenously (IV) for 5 days. Mesna was given IV every 4 hours for three doses after ifosfamide administration at a dose of 20% of the daily ifosfamide dose. All patients with ovarian cancer and 87% of those with cervical cancer had had prior platinum-based therapy. Because of the toxicity encountered in previously treated patients with ovarian carcinoma, the dose of ifosfamide was reduced to 1.2 g/m2/d in those who had had prior chemotherapy or radiotherapy. In epithelial ovarian carcinoma, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses (CRs). Response duration was 2.1 to 20.3+ months (median, 6.9+ months). In squamous carcinoma of the cervix, 3 (11.1%) of 27 evaluable patients had partial responses (PRs) of 1.8-, 2.2-, and 3.1-month duration. Of 26 untreated patients with mixed mesodermal tumors of the uterus, 5 (19.2%) had CRs and 3 (11.5%) had PRs, for an overall response rate of 30.7%. Response duration was 1.4+ to 8.6 months, with a median of 3.8 months. Toxicity included two deaths from renal insufficiency and a third related to neurologic impairment. Hematologic toxicity was manageable. Ifosfamide/mesna has activity in a wide range of gynecologic malignancies.

Gynecologic Oncology Group studies with ifosfamide.

The Gynecologic Oncology Group has conducted a series of phase II studies with ifosfamide and mesna since 1985. Previously untreated patients received ifosfamide 1.5 g/m2 intravenously daily for 5 days. Mesna was given intravenously every 4 hours three times daily at 20% of the daily ifosfamide dose. Because of the toxic effects observed in previously treated patients with ovarian cancer, the ifosfamide dose was reduced to 1.2 g/m2/d in patients with prior chemotherapy or radiotherapy. In epithelial ovarian cancer, responses were observed in eight (20%) of 41 evaluable patients, with three (7%) complete responses. In patients with squamous carcinoma of the cervix, an 11.1% response rate (three of 27 patients) was observed in those who had received prior platinum therapy. In 51 previously untreated patients, the response rate was 15.7%. In nonsquamous cervical carcinomas, there were three partial responses among 25 patients (12%). An 8.6% response rate was observed among 23 patients with previously treated endometrial adenocarcinomas. In uterine sarcomas, response rates were 30.7% in mixed müllerian tumors, 17.2% in leiomyosarcomas, and 27.3% in endometrial stromal sarcomas. Patients with ovarian sarcomas responded in 27.8% of cases. Studies with ifosfamide combinations are currently under way by the Gynecologic Oncology Group.

Adenocarcinoma corpus et colli: analysis of diagnostic variables.

Between January 1973 and December 1983, 469 patients with carcinoma of the endometrium were seen at this institution. Eighty-one patients were identified with adenocarcinoma involving both the uterine body and the cervix. Patients were divided into three groups for evaluation. Group A (n = 58) had a positive cervical biopsy or endocervical curettage, but a normal-appearing cervix at clinical examination. Group B (n = 18) had gross tumor involving the cervix which was confirmed by biopsy. Group C (n = 5) had unsuspected cervical involvement revealed at hysterectomy. Fourteen Group A patients received preoperative radiation therapy. Thirty of the 44 Group A patients (68.2%) who did not receive preoperative radiation, had no involvement of the cervix by tumor in the hysterectomy specimen. Seventy-six patients were eligible for follow-up of at least 18 months. There were 24 recurrences among these 76 patients. Recurrence was more common with advancing grade and with increasing myometrial invasion. Pelvic failures occurred with comparable frequency in both Groups A and B. Only 4 of 11 patients who were found to have extrauterine disease at surgery are still alive. In this study, we found that endocervical curettage has a significant false-positive rate, both histologic grade and volume of cervical involvement should be considered in treatment planning, primary operation should be considered in the management of selected patients with Stage II endometrial carcinoma, and extrauterine disease is a grave prognostic factor.