Investigation into the foundations of the track-event theory of cell survival and the radiation action model based on nanodosimetry

This work aims at elaborating the basic assumptions behind the “track-event theory” (TET) and its derivate “radiation action model based on nanodosimetry” (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency of single and clustered DNA lesions are dispensable for multi-event distributions because they follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that making these assumptions for the single-event distributions of the number of lethal and sublethal lesions within a cell would lead to an essentially exponential dose dependence of survival for practically relevant values of the absorbed dose. Furthermore, it is elucidated that the model equation used for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently. Consequently, the model equation is presumably inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the methodology for deriving model parameters from nanodosimetric properties of particle track structure is critically assessed. Based on data from proton track simulations it is shown that the assumption of statistically independent targets leads to the prediction of negligible frequency of clustered DNA damage. An approach is outlined how track structure could be considered in determining the model parameters, and the implications for TET and RAMN are discussed.

     

Pterosaur Stance and Gait and the Interpretation of Trackways

The tracks ascribed to pterosaurs from the Late Jurassic limestones at Crayssac, France, must be pterosaurian because the manus prints are so far outside those of the pes, the pes print is four times longer than wide, and the manus prints appear to preserve distinct traces of a posteromedially directed wing-finger. These tracks are different in important ways from previously described Pteraichnus trackways, which have been variably considered pterosaurian, crocodilian, or indeterminate. No Pteraichnus (sensu stricto: those not from Crayssac) tracks have diagnostic features of pterosaurs and in none can a complete phalangeal or digital formula be reconstructed; however, all published Pteraichnidae tracks fulfill the criteria of poor preservation, and some have some diagnostic features of crocodile tracks. Reconstructions of pterosaurs walking in pteraichnid tracks do not fit those tracks well, but crocodiles do. In contrast, the Crayssac tracks demonstrate the erect stance and parasagittal gait previously reconstructed for pterosaurs. They also demonstrate that the footfall pattern was not as in typical reptiles (LH-RF-RH-LF), but that the manus must have been raised before the next forward step of the ipselateral foot (LH-LF-RH-RF), suggesting that the quadrupedal pattern was secondary. The metatarsus in pterosaurs was set low at the beginning of a stride, as it is in crocodilians and basal dinosaurs. The diagnosis of the Ichnofamily Pteraichnidae comprises features of possible crocodilian trackmakers, but not of possible pterosaurian trackmakers. Trackways considered for attribution to pterosaurs should show (1) manus prints up to three interpedal widths from midline of body, and always lateral to pes prints, (2) pes prints four times longer than wide at the metatarso-phalangeal joint, and (3) penultimate phalanges longest among those of the pes.     

New modelling of complex fish migration by application of chaos theory and neural network

Rules or patterns of movement or migration were still vague even for the main commercial fishes due to different routs in scale or in different, times resulting from complex environments to complex behaviour concept. The quantitative model of fish migration has been investigated using chaos theory to mimic more realistic fish movements by time steps from environmental and biological stimuli. The model uses three steps within a model neural network such as input stimuli, central decision‐making and response output in fish movements. The stimuli in the first step include the main physical (temperature, salinity, light, flow etc .) and biotic factors (prey, predator, life cycle etc .) which could be quantified as intensity parameters which were then normalized as ratios. The decision‐making process can be generated available signals for motor neuron using Lorenz chaos equations by the relevant stimuli. The response of fish movements from the output signal representing speed and direction can be re‐regulated as object‐oriented migration depending on physiological state or life cycle by third response filtering. The simulation results seen as 2‐dimensional seasonal migration for demersal fishes in the southern sea of the Korean Peninsula represented more realistic meandering tracks than the interpolated tracks in previous reports.     

A model for the separation of large DNA molecules by crossed field gel electrophoresis.

The idea that large DNA molecules adopt a stretched conformation as they pass through gels suggests a simple mechanism for the separation of DNA by crossed field electrophoresis: at each change in field direction a DNA molecule takes off in the new direction of the field by a movement which is led by what was formerly its back end. The effect of this ratcheting motion is to subtract from the DNA molecule's forward movement, at each step, an amount which is proportional to its length. We find that this model explains most of the features of the separation, and we describe experiments, using a novel electrophoresis apparatus, which support the model. The apparatus turns the gel between two preset orientations in a uniform electric field at preset time intervals. This separation method has the practical advantage over some others that the DNA molecules follow straight tracks. A further advantage is that the parameters which determine the separation are readily predicted from the simple theory describing their motion.     

DNA complex lesions induced by protons and ⋅-particles: track structure characteristics determining linear energy transfer and particle type dependence

The yield of DNA double-strand breaks (dsb) and DNA complex lesions induced by protons and α-particles of various energies was simulated using a Monte Carlo track structure code (MOCA15) and a simple model of the DNA molecule. DNA breaks of different complexity were analysed. The linear energy transfer (LET) and particle-type dependence of lesions of higher complexity seems to confirm the importance of clustered damage in DNA as a relevant step leading to biological endpoints such as cell inactivation. The detailed structure of proton and α-particle tracks was analysed to identify the main characteristics possibly responsible for such a dependence. The role of the primary ion and of its secondary electrons in inducing dsb and complex lesions is described, showing that the relative contribution of secondary electron tracks alone in inducing clustered lesions is almost negligible at high LET, but tends to dominate below ≈10 keV/μm. This is consistent with the observed similar effectiveness of low-LET fast particle radiation and sparsely ionizing radiation such as x-rays. The dependence on LET and particle type is mainly due to energy deposition events of the primary ion together with short range electrons surrounding the ion track; the yield of complex lesions due to secondary electron tracks alone is substantially LET independent. The radial distributions of the energy contributing to the induction of complex lesions were analyzed and compared with the radial distributions of energy deposition of the full tracks. The results suggest that the stochastic behaviour (i.e. cluster properties) of the energy deposition pattern within a radius of a few nanometers around the ion track plays a relevant role in determining the biological radiation effectiveness. Received: 20 December 1996 / Accepted in revised form: 5 March 1997     

A CFD model for predicting protein aggregation in low-pH virial inactivation for mAb production

Significant amounts of soluble product aggregates were observed in the low-pH viral inactivation (VI) operation during an initial scale-up run for an immunoglobulin-G 4 (IgG4) monoclonal antibody (mAb IgG4-N1). Being earlier in development, a scale-down model did not exist, nor was it practical to use costly Protein A eluate (PAE) for testing the VI process at scale, thus, a computational fluid dynamics (CFD)-based high-molecular weight (HMW) prediction model was developed for troubleshooting and risk mitigation. It was previously reported that the IgG4-N1 molecules upon exposure to low pH tend to change into transient and partially unfolded monomers during VI acidification (i.e., VIA) and form aggregates after neutralization (i.e., VIN). Therefore, the CFD model reported here focuses on the VIA step. The model mimics the continuous addition of acid to PAE and tracks acid distribution during VIA. Based on the simulated low-pH zone (≤pH 3.3) profiles and PAE properties, the integrated low-pH zone (ILPZ) value was obtained to predict HMW level at the VI step. The simulations were performed to examine the operating parameters, such as agitation speed, acid addition rate, and protein concentration of PAE, of the pilot scale (50–200 L) runs. The conditions with predictions of no product aggregation risk were recommended to the real scale-up runs, resulted in 100% success rate of the consecutive 12 pilot-scale runs. This study demonstrated that the CFD-based HMW prediction model could be used as a tool to facilitate the scale up of the low-pH VI process directly from bench to pilot/production scale.     

The influence of track compliance on running

A model of running is proposed in which the leg is represented as a rack-and-pinion element in series with a damped spring. The rack-and-pinion element emphasizes the role of descending commands, while the damped spring represents the dynamic properties of muscles and the position and the rate sensitivity of reflexes. This model is used to predict separately the effect of track compliance on step length and ground contact time. The predictions are compared with experiments in which athletes ran over tracks of controlled spring stiffness. A sharp spike in foot force up to 5 times body weight was found on hard surfaces, but this spike disappeared as the athletes ran on soft experimental tracks. Both ground contact time and step length increased on very compliant surfaces, leading to moderately reduced running speeds, but a range of track stiffness was discovered which actually enhances speed.     

Navigation Strategies of Motor Proteins on Decorated Tracks

Motor proteins display widely different stepping patterns as they move on microtubule tracks, from the deterministic linear or helical motion performed by the protein kinesin to the uncoordinated random steps made by dynein. How these different strategies produce an efficient navigation system needed to ensure correct cellular functioning is still unclear. Here, we show by numerical simulations that deterministic and random motor steps yield different outcomes when random obstacles decorate the microtubule tracks: kinesin moves faster on clean tracks but its motion is strongly hindered on decorated tracks, while dynein is slower on clean tracks but more efficient in avoiding obstacles. Further simulations indicate that dynein’s advantage on decorated tracks is due to its ability to step backwards. Our results explain how different navigation strategies are employed by the cell to optimize motor driven cargo transport.     

Can vector summation describe the orientation system of juvenile ospreys and honey buzzards? – An analysis of ring recoveries and satellite tracking

Juvenile bird migrants are generally believed to use a clock‐and‐compass migratory orientation strategy. According to such a strategy migrants accomplish their migration by flying a number of successive flight steps with direction and number of steps controlled by an endogenous programme. One powerful way of testing this is by comparing predictions from a model of such a strategy with observed patterns. We used data from ringing and satellite‐based radio telemetry to investigate the orientation system of juvenile ospreys (Pandion haliaetus) and honey buzzards (Pernis apivorus) migrating from Sweden to tropical west Africa. The ring recoveries showed a much larger scatter in the orientation of ospreys than of honey buzzards, but there was only a slight such difference in the satellite tracks. These tracks of individuals of both species were rather straight with a high directional concentration per step. The honey buzzard data showed a close fit to a simple vector summation model, which is expected if birds follow a clock‐and‐compass strategy. However, the osprey data did not fit such a simple model, as ring recoveries showed a significantly greater deviation at short distances than predicted on the basis of long distance data. Satellite tracking also indicated less concentrated orientation on short distances. The pattern observed for the osprey can generally be explained by an extended vector summation model, including an important element of pre‐migration dispersal. The existence of extensive dispersal in the osprey stands in contrast to the apparent absence of such dispersal in the honey buzzard. The explanation for this difference between the species is unclear. The model of orientation by vector summation is very sensitive to the existence of differences in mean direction between individuals. Assuming such differences, as tentatively indicated by the satellite tracking data, makes simple compass orientation by vector summation inconsistent with the distribution of ring recoveries at long distances, with a high proportion of misoriented birds falling outside the normal winter range.     

Kinesin's walk: Springy or gated head coordination?

Conventional kinesin (kinesin-1) is a motor protein that performs a vital function in the eukaryotic cell: it actively transports cargo to required destinations. Kinesin pulls cargo along microtubule tracks using twin linked motor domains (heads) that bind the microtubule, hydrolyse ATP, and alternately step forward. The detail of the kinesin walk has yet to be discovered but a prominent theory is that the mechanism is rectified Brownian motion (RBM) biased by linker zippering. There is evidence that an ATP binding gate coordinates the heads. The hypothesis proposed here is that the gate is unnecessary, that entropic linker strain is sufficient to enable procession. An agent-based computer simulation has been devised to explore head coordination in the RBM model. Walking was found to emerge in silico without a gate to synchronise the heads. Further investigation of the model by applying a range of hindering loads resulted in backstepping or detachment with similar characteristics to behaviour observed in vitro. It is unclear whether kinesin waits at an obstacle but adding an ATP hydrolysis gate to the model in order to force waiting resulted in the model behaving less realistically under load. It is argued here that an RBM model free of gating is a good candidate for explaining kinesin procession.     

A Darwinian evolutionary system. 3. Experiments on the evolution of feeding patterns

Another application of the Darwinian evolutionary system introduced earlier is presented. The evolution of spiraling and meandering feeding patterns, as exemplified by the marine polychaete Paraonis fulgens, was simulated by constructing an artificial “worm”, called Rectangulus, because it was capable of turning around 90 ° only. The behavioural program of Rectangulus contained six parameters, which controlled the following properties: (i) turning spontaneously after a given number of steps, (ii) turning before a former track, (iii) avoiding entering a “channel”, i.e. a path flanked by former tracks, (iv) keeping contact with former tracks, (v) performing a turn at the beginning (which in combination with contact-keeping leads to a spiral), and (vi) switching from spiraling to meandering behaviour after a given number of steps. These parameters were binary-coded in the “genomes” of Rectangulus, and were capable of mutating and recombining.Evolutionary experiments were performed with populations consisting of 50 individuals, inhabiting an area of 100 × 100 “unit steps”. Each individual had to “forage” for 140 steps, and the number of successful (uncovered area) and unsuccessful (area covered previously) steps were recorded. Individuals with greater “yield” (successful minus unsuccessful steps, divided by the total number of steps) had a greater probability of being reproduced (selection). It was found that Rectangulus soon “learned” to turn in front of a former track and a channel, and to keep contact, both if one starts with individuals who at the beginning could only go straight ahead, or with ones turning after every step. Evolution from this stage onward proceeded more variably. Different types of meandering, spiraling, and a combination of both emerged; however, in two out of six cases, evolution did not proceed beyond the turning and contact-keeping stage. It is suggested that the different outcomes represent separate adaptive peaks. The highest yield was obtained by the combination of spiraling and meandering, as used by Paraonis fulgens, followed by pure spiraling and meandering. This was confirmed by calculations made for populations with fixed parameters. The results further show that selection for non-crossing could only have been effective in producing these patterns for population densities much higher than the ones found for P. fulgens at the present time.     

Inter‐colony foraging area segregation quantified in small colonies of Adélie Penguins

Theoretical models on the movement of colonial animals predict that neighbouring colonies may segregate their foraging areas, and many seabird studies have reported the presence of such segregations. However, these studies have often lacked the appropriate null model to test the effect of neighbouring colonies on foraging areas, especially in small colonies or in short‐ranging species. Here, we examined the foraging areas of Adélie Penguins Pygoscelis adeliae from two neighbouring (2 km apart) colonies by using bird‐borne GPS loggers. The field study was conducted at Hukuro Cove colony (104 pairs) and Mizukuguri Cove colony (338 pairs) in Lützow‐Holm Bay, East Antarctica. We obtained GPS tracks for 504 foraging trips from 48 chick‐rearing Adélie Penguins and quantified the degree of overlap in the foraging areas between two colonies. We also produced simulated movement tracks by using correlated random‐walks assuming no inter‐colony competition and quantified the degree of overlap in the simulated foraging areas. Finally, we compared the results from real GPS tracks with those from simulated tracks to examine the effect of neighbouring colonies on Adélie Penguin movement. The results indicate that the degree of overlap was significantly smaller in real tracks than in simulated tracks. In real tracks, the foraging area of the smaller Hukuro Cove colony extended to the other side of the larger Mizukuguri Cove colony, unlike in simulated tracks. Consequently, we suggest that Adélie Penguins from two neighbouring colonies segregated their foraging areas and that the larger colony appeared to affect the foraging area of the smaller colony.     

Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules

In epithelial cells, polarized growth and maintenance of apical and basolateral plasma membrane domains depend on protein sorting from the trans-Golgi network (TGN) and vesicle delivery to the plasma membrane. Septins are filamentous GTPases required for polarized membrane growth in budding yeast, but whether they function in epithelial polarity is unknown. Here, we show that in epithelial cells septin 2 (SEPT2) fibers colocalize with a subset of microtubule tracks composed of polyglutamylated (polyGlu) tubulin, and that vesicles containing apical or basolateral proteins exit the TGN along these SEPT2/polyGlu microtubule tracks. Tubulin-associated SEPT2 facilitates vesicle transport by maintaining polyGlu microtubule tracks and impeding tubulin binding of microtubule-associated protein 4 (MAP4). Significantly, this regulatory step is required for polarized, columnar-shaped epithelia biogenesis; upon SEPT2 depletion, cells become short and fibroblast-shaped due to intracellular accumulation of apical and basolateral membrane proteins, and loss of vertically oriented polyGlu microtubules. We suggest that septin coupling of the microtubule cytoskeleton to post-Golgi vesicle transport is required for the morphogenesis of polarized epithelia.     

Foraging efficiency and the fitness consequences of spatial marking by ladybeetle larvae

Marking and avoiding poor‐quality resources can be an important mechanism by which animals lacking a spatial memory can maximize their foraging efficiency. Here, we investigate the behaviour of larval Harmonia axyridis ladybeetles that leave chemical tracks as they forage. We built a model of an individual larva foraging for aphids, parameterized it using experimental data, and used the model to predict the effect of larval track production and detection on foraging efficiency, an important component of fitness. The model predicted that there is an optimal sensitivity of larvae to tracks which maximizes foraging efficiency; if the larva is too sensitive to tracks, it will avoid areas that might still contain resources, whereas if it is too insensitive, it will forage in areas that have depleted resources. Furthermore, the increased efficiency conferred by detecting tracks depends on the spatial arrangement of resources, with more aggregated resource distributions allowing greater benefits of detecting tracks. We tested the predictions of the model experimentally by measuring predation on aggregated versus dispersed soybean aphids by H. axyridis larvae whose ability to produce tracks was experimentally manipulated. The experiments corroborated the results of the model: larvae that could produce tracks consumed more aphids than those that could not, and this difference was greatest when aphids were aggregated among plants. Our results suggest that larval tracks play an important role in foraging efficiency, and we discuss implications for the evolution of larval track production and detection in ladybeetles.     

Migration route selection of juvenile Chinook salmon at the Delta Cross Channel, and the role of water velocity and individual movement patterns

We examined movement tracks of ultrasonic-tagged juvenile Chinook salmon (Oncorhynchus tshawyscha) smolts at the juncture of two migratory pathways. This migratory juncture occurs where the Delta Cross Channel splits from the Sacramento River in California’s Sacramento–San Joaquin Delta. Smolt tracks were analyzed to compare the importance of river flow and individual parameters in migratory route selection. The two routes differ significantly in smolt survival probabilities (Perry et al. N Am J Fish Manag 30:142–156, 2010), thus a clearer understanding of the variables contributing to route selection will be valuable for management of this declining species. A comparison of the two migratory groups showed that fish remaining within the Sacramento River: 1) Encountered the migratory juncture when river water velocities were much higher than those in the Delta Cross Channel (p?<?0.0001), 2) showed more direct swimming paths (p?=?0.03) and 3) migrated at higher speeds (p?=?0.04). Logistic regression models showed that the ratio of mean water velocity between the two routes was a much stronger predictor of ultimate route selection than any other variable tested. However, parameters for both the lateral position of smolts within the river and smolt size added predictive power to the final model. Our results suggest that river flow remains the most important variable for predicting smolt migration route, but note that knowledge of individual smolt attributes and movement patterns can increase our predictive ability.     

Running on flat turns: experiments, theory, and applications

Theoretical and experimental results are presented which demonstrate the mechanical effects of running along a circular turn. The theory is a simple one-parameter model, requiring only the top speed Vo of the runner as an input. The dimensionless parameter (Rg/v2o), a reciprocal Froude number or dimensionless parameter (Rg/v20), a reciprocal Froude number or dimensionless radius, appears as a natural result of the theory. This radial Froude number allows for the comparison of the theory and experiment for a large number of individuals on the same set of axes. The parameters of speed, foot contact time, ballistic air time, step length, stride length, and stride time are all predicted and measured for 23 different subjects. The agreement between theory and experiment is good. Exact solutions and approximate asymptotic results for the speed-radius relation are presented. Applications are made to the practical problem of the design of indoor and outdoor running tracks for athletic competition.     

Determining Observer Reliability in Counts of River Otter Tracks

ABSTRACT In many research projects, reliability of collected data is dependent on reliability of field observers. However, it is uncommon for observer reliability to be either measured or reported in wildlife research. We tested whether observer skill affected outcomes of a northern river otter (Lontra canadensis) track survey conducted by the Texas Parks and Wildlife Department. Observers recorded presence of tracks at bridge sites (n = 250) throughout a 27-county region in east Texas, USA. Logistic regression indicated that observers were significantly associated with frequency of reported otter tracks. Because observers were not assigned to bridges at random, we tested and found associations between the bridges surveyed by each observer (SURVEY ROUTE) and habitat variables (WATERSHED, VEGETATION-TYPE, WATER-TYPE, BRIDGE-AREA) that may have influenced otter presence and probability of detection. A standardized tracker evaluation procedure indicated that experienced observers (n = 7) misidentified 37% of otter tracks. Additionally, 26% of tracks from species determined to be “otter-like” were misidentified as otter tracks. We recommend that observer skill in identification of animal tracks and other indirect signs be measured to detect and reduce observer errors in wildlife monitoring.     

America's Most Famous Human Footprints: History,Context and First Description of Mid-Holocene Tracks from the Shores of Lake Managua,Nicaragua

Human tracks discovered in 1874 at a site named El Cauce or Acahualinca near the shores of Lake Managua, Nicaragua, are the most famous and abundant human tracks in the Americas. They represent a landmark ichnological discovery during the late 19th century that generated much debate regarding their age and origins. Reported dates for the tracks range from 2,120 to 6,500 B.P. The site, which is now situated within the limits of Nicaragua's capital city of Managua, forms the basis of the Acahualinca Tracks Museum (Huellas de Acahualinca) and has been in place since 1953. However, it is still little known and has not been systematically studied, despite being an important window into Meso-American prehistory. Two exposures of a surface of volcanic ash reveal hundreds of human tracks comprising a minimum of 12 clearly defined trackways, and a trampled zone or path representing at least three more individuals, all heading in the same northwesterly direction. Tracks of deer, opossum and at least one bird are also present. Bison tracks collected from another nearby site (El Recreo) that is no longer accessible are on display at the museum. The Acahualinca tracks are noteworthy for the exceptional quality of preservation. We herein present the first maps of the two exposures, which combine to tell a story of human and animal activity along the shores of ancient Lake Managua several thousand years ago.     

Late Albian Dinosaur Tracks from the Cratonic (Eastern) Margin of the Western Interior Seaway,Nebraska, USA

At least 22 tridactyl dinosaur tracks, poorly preserved in various degrees of expression, have recently been found at an exposure in the Dakota Formation (Lower Cretaceous, Albian) in Jefferson County, Nebraska. These tracks generally have broad, blunt digits and a broad posterior margin. The largest of the tracks measures 57 cm in length and 58 cm in width. All of the tracks lie within a stratigraphic horizon of 40 cm or less, but they do not form a single trackway. We interpret the trackmakers to have been ornithopods.

The Jefferson County tracks are in a well-cemented sandstone with oscillation ripples, at a stratigraphic level between two well-established sequence boundaries. Channel forms and lateral accretion units are common in the stratigraphic interval enclosing the tracks, and the site is interpreted as a bar or sand flat in a tidally influenced river.

The Jefferson County tracks are only the second known occurrence of large Mesozoic tetrapod tracks east of the Rocky Mountain Front-High Plains Margin, including the Black Hills of South Dakota, west of the Atlantic Coastal Plain, and north of the Gulf Coastal Plain. Further, this paper is the first documentation of in situdinosaur fossils from the Nebraska-Iowa area.