Neural Control of Interlimb Coordination and Gait Timing in Bipeds and Quadrupeds

1) A large body of behavioral data conceming animal and human gaits and gait transitions is simulated as emergent properties of a central pattern generator (CPG) model. The CPG model incorporates neurons obeying Hodgkin-Huxley type dynamics that interact via an on-center off-surround anatomy whose excitatory signals operate on a faster time scale than their inhibitory signals. A descending cornmand or arousal signal called a GO signal activates the gaits and controL their transitions. The GO signal and the CPG model are compared with neural data from globus pallidus and spinal cord, among other brain structures. 2) Data from human bimanual finger coordination tasks are simulated in which anti-phase oscillations at low frequencies spontaneously switch to in-phase oscillations at high frequencies, in-phase oscillations can be performed both at low and high frequencies, phase fluctuations occur at the anti-phase in-phase transition, and a "seagull effect" of larger errors occurs at intermediate phases. When driven by environmental patterns with intermediate phase relationships, the model's output exhibits a tendency to slip toward purely in-phase and anti-phase relationships as observed in humans subjects. 3) Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop) and the pronk are simulated. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. 4) Precise control of quadruped gait switching is achieved in the model by using GO-dependent modulation of the model's inhibitory interactions. This generates a different functional connectivity in a single CPG at different arousal levels. Such task-specific modulation of functional connectivity in neural pattern generators has been experimentally reported in invertebrates. Phase-dependent modulation of reflex gain has been observed in cats. A role for state-dependent modulation is herein predicted to occur in vertebrates for precise control of phase transitions from one gait to another. 5) The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are sirnulated. Although these two gaits are qualitatively different, they both have the same limb order and may exhibit oscillation frequencies that overlap. The CPG model simulates the walk and the run by generating oscillations which exhibit the same phase relationships. but qualitatively different waveform shapes, at different GO signal levels. The fraction of each cycle that activity is above threshold quantitatively distinguishes the two gaits, much as the duty cycles of the feet are longer in the walk than in the run. 6) A key model properly concerns the ability of a single model CPG, that obeys a fixed set of opponent processing equations to generate both in-phase and anti-phase oscillations at different arousal levels. Phase transitions from either in-phase to anti-phase oscillations, or from anti-phase to in-phase oscillations, can occur in different parameter ranges, as the GO signal increases.

Functional metagenomic analysis of the human gut microbiome to identify novel salt tolerance genes

The ability to adapt to and respond to increases in external osmolarity is an important characteristic that enables bacteria to survive and proliferate in different environmental niches. When challenged with increased osmolarity, due to sodium chloride (NaCl) for example, bacteria elicit a phased response; firstly via uptake of potassium (K+), which is known as the primary response. This primary response is followed by the secondary response which is characterised by the synthesis or uptake of compatible solutes (osmoprotectants). The overall osmotic stress response is much broader however, involving many diverse cellular systems and processes. These ancillary mechanisms are arguably more interesting and give a more complete view of the osmotic stress response. The aim of this thesis was to identify novel genetic loci from the human gut microbiota that confer increased tolerance to osmotic stress using a functional metagenomic approach. Functional metagenomics is a powerful tool that enables the identification of novel genes from as yet uncultured bacteria from diverse environments through cloning, heterologous expression and phenotypic identification of a desired trait. Functional metagenomics does not rely on any previous sequence information to known genes and can therefore enable the discovery of completely novel genes and assign functions to new or known genes. Using a functional metagenomic approach, we have assigned a novel function to previously annotated genes; murB, mazG and galE, as well as a putative brp/blh family beta-carotene 15,15’-monooxygenase. Finally, we report the identification of a completely novel salt tolerance determinant with no current known homologues in the databases. Overall the genes identified originate from diverse taxonomic and phylogenetic groups commonly found in the human gastrointestinal (GI) tract, such as Collinsella and Eggerthella, Akkermansia and Bacteroides from the phyla Actinobacteria, Verrucomicrobia and Bacteroidetes, respectively. In addition, a number of the genes appear to have been acquired via lateral gene transfer and/or encoded on a prophage. To our knowledge, this thesis represents the first investigation to identify novel genes from the human gut microbiota involved in the bacterial osmotic stress response.

Networks versus vertical integration

We construct a theory to compare vertically integrated firms to networks of manufacturers and suppliers. Vertically integrated firms make their own specialized inputs. In networks, manufacturers procure specialized inputs from suppliers that, in turn, sell to several manufacturers. The analysis shows that networks can yield greater social welfare when manufacturers experience large idiosyncratic demand shocks. Individual firms may also have the incentive to form networks, despite the lack of long-term contracts. The analysis is supported by existing evidence and provides predictions as to the shape of different industries.

Hippocampus shape analysis and late-life depression.

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F(1,103) = 5.26; p = 0.0240) but not right hippocampus volume (F(1,103) = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms.

Monte Carlo Analysis and Physics Characterization of a Novel Nanoparticle Detector for Medical and Micro-dosimetry Applications

The outcomes for both (i) radiation therapy and (ii) preclinical small animal radio- biology studies are dependent on the delivery of a known quantity of radiation to a specific and intentional location. Adverse effects can result from these procedures if the dose to the target is too high or low, and can also result from an incorrect spatial distribution in which nearby normal healthy tissue can be undesirably damaged by poor radiation delivery techniques. Thus, in mice and humans alike, the spatial dose distributions from radiation sources should be well characterized in terms of the absolute dose quantity, and with pin-point accuracy. When dealing with the steep spatial dose gradients consequential to either (i) high dose rate (HDR) brachytherapy or (ii) within the small organs and tissue inhomogeneities of mice, obtaining accurate and highly precise dose results can be very challenging, considering commercially available radiation detection tools, such as ion chambers, are often too large for in-vivo use.

In this dissertation two tools are developed and applied for both clinical and preclinical radiation measurement. The first tool is a novel radiation detector for acquiring physical measurements, fabricated from an inorganic nano-crystalline scintillator that has been fixed on an optical fiber terminus. This dosimeter allows for the measurement of point doses to sub-millimeter resolution, and has the ability to be placed in-vivo in humans and small animals. Real-time data is displayed to the user to provide instant quality assurance and dose-rate information. The second tool utilizes an open source Monte Carlo particle transport code, and was applied for small animal dosimetry studies to calculate organ doses and recommend new techniques of dose prescription in mice, as well as to characterize dose to the murine bone marrow compartment with micron-scale resolution.

Hardware design changes were implemented to reduce the overall fiber diameter to <0.9 mm for the nano-crystalline scintillator based fiber optic detector (NanoFOD) system. Lower limits of device sensitivity were found to be approximately 0.05 cGy/s. Herein, this detector was demonstrated to perform quality assurance of clinical 192Ir HDR brachytherapy procedures, providing comparable dose measurements as thermo-luminescent dosimeters and accuracy within 20% of the treatment planning software (TPS) for 27 treatments conducted, with an inter-quartile range ratio to the TPS dose value of (1.02-0.94=0.08). After removing contaminant signals (Cerenkov and diode background), calibration of the detector enabled accurate dose measurements for vaginal applicator brachytherapy procedures. For 192Ir use, energy response changed by a factor of 2.25 over the SDD values of 3 to 9 cm; however a cap made of 0.2 mm thickness silver reduced energy dependence to a factor of 1.25 over the same SDD range, but had the consequence of reducing overall sensitivity by 33%.

For preclinical measurements, dose accuracy of the NanoFOD was within 1.3% of MOSFET measured dose values in a cylindrical mouse phantom at 225 kV for x-ray irradiation at angles of 0, 90, 180, and 270˝. The NanoFOD exhibited small changes in angular sensitivity, with a coefficient of variation (COV) of 3.6% at 120 kV and 1% at 225 kV. When the NanoFOD was placed alongside a MOSFET in the liver of a sacrificed mouse and treatment was delivered at 225 kV with 0.3 mm Cu filter, the dose difference was only 1.09% with use of the 4x4 cm collimator, and -0.03% with no collimation. Additionally, the NanoFOD utilized a scintillator of 11 µm thickness to measure small x-ray fields for microbeam radiation therapy (MRT) applications, and achieved 2.7% dose accuracy of the microbeam peak in comparison to radiochromic film. Modest differences between the full-width at half maximum measured lateral dimension of the MRT system were observed between the NanoFOD (420 µm) and radiochromic film (320 µm), but these differences have been explained mostly as an artifact due to the geometry used and volumetric effects in the scintillator material. Characterization of the energy dependence for the yttrium-oxide based scintillator material was performed in the range of 40-320 kV (2 mm Al filtration), and the maximum device sensitivity was achieved at 100 kV. Tissue maximum ratio data measurements were carried out on a small animal x-ray irradiator system at 320 kV and demonstrated an average difference of 0.9% as compared to a MOSFET dosimeter in the range of 2.5 to 33 cm depth in tissue equivalent plastic blocks. Irradiation of the NanoFOD fiber and scintillator material on a 137Cs gamma irradiator to 1600 Gy did not produce any measurable change in light output, suggesting that the NanoFOD system may be re-used without the need for replacement or recalibration over its lifetime.

For small animal irradiator systems, researchers can deliver a given dose to a target organ by controlling exposure time. Currently, researchers calculate this exposure time by dividing the total dose that they wish to deliver by a single provided dose rate value. This method is independent of the target organ. Studies conducted here used Monte Carlo particle transport codes to justify a new method of dose prescription in mice, that considers organ specific doses. Monte Carlo simulations were performed in the Geant4 Application for Tomographic Emission (GATE) toolkit using a MOBY mouse whole-body phantom. The non-homogeneous phantom was comprised of 256x256x800 voxels of size 0.145x0.145x0.145 mm3. Differences of up to 20-30% in dose to soft-tissue target organs was demonstrated, and methods for alleviating these errors were suggested during whole body radiation of mice by utilizing organ specific and x-ray tube filter specific dose rates for all irradiations.

Monte Carlo analysis was used on 1 µm resolution CT images of a mouse femur and a mouse vertebra to calculate the dose gradients within the bone marrow (BM) compartment of mice based on different radiation beam qualities relevant to x-ray and isotope type irradiators. Results and findings indicated that soft x-ray beams (160 kV at 0.62 mm Cu HVL and 320 kV at 1 mm Cu HVL) lead to substantially higher dose to BM within close proximity to mineral bone (within about 60 µm) as compared to hard x-ray beams (320 kV at 4 mm Cu HVL) and isotope based gamma irradiators (137Cs). The average dose increases to the BM in the vertebra for these four aforementioned radiation beam qualities were found to be 31%, 17%, 8%, and 1%, respectively. Both in-vitro and in-vivo experimental studies confirmed these simulation results, demonstrating that the 320 kV, 1 mm Cu HVL beam caused statistically significant increased killing to the BM cells at 6 Gy dose levels in comparison to both the 320 kV, 4 mm Cu HVL and the 662 keV, 137Cs beams.

CFD approach for solid mechanics analysis

A cell-centred finite volume(CC-FV) solid mechanics formulation, based on a computational fluid dynamics(CFD) procedure, is presented. A CFD code is modified such that the velocity variable is used as to the displacement variable. Displacement and pressure fields are considered as unknown variables. The results are validated with finite element(FE) and cell-vertex finite volume(CV-FV) predictions based on discretisation of the equilibrium equations. The developed formulation is applicable for both compressible and incompressible solids behaviour. The method is general and can be extended for the simultaneous analysis of problems involving flow-thermal and stress effects.

Thermo-mechanical analysis of the packaging process for micro-electronic displays

Micro-electronic displays are sensitive devices and its performance is easily affected by external environmental factors. To enable the display to perform in extreme conditions, the device must be structurally strengthened, the effects of this packaging process was investigated. A thermo-mechanical finite element analysis was used to discover potential problems in the packaging process and to improve the overall design of the device. The main concern from the analysis predicted that displacement of the borosilicate glass and the Y stress of the adhesive are important. Using this information a design which reduced the variation of displacement and kept the stress to a minimum was suggested

Impact of the vertical potshell deformation on the MHD cell stability behavior of a 500 kA aluminium electrolysis cell

In previous publications [1,2], it was rationalized that a large vertical potshell deformation may have a negative impact on the operations of very high amperage cells. The MHD-Valdis non-linear Magneto-Hydro-Dynamic model was therefore extended to take into account the displacement of the potshell. The MHD cell stability behavior of a 500 kA cell with a 17.3 meters long potshell was then studied.

The UK 9/11 evacuation study: Analysis of survivors’ recognition and response phase in WTC1

The September 11th 2001 impact on the World Trade Centre (WTC) resulted in one of the most significant evacuations of a high-rise building in modern times. The UK High-rise Evacuation Evaluation Database (HEED) study aimed to capture and collate the experiences and behaviours of WTC evacuees in a database, which would facilitate and encourage future research, which in turn would influence the design construction and use of safer built environments. A data elicitation tool designed for the purpose comprised a pre-interview questionnaire followed by a one-to-one interview protocol consisting of free-flow narratives and semi-structured interviews of WTC evacuees. This paper, which is one in a series dealing with issues relating to the successful evacuations of towers 1 and 2, focuses on cue recognition and response patterns within WTC1. Results are presented by vertical floor clusters and include information regarding cues experienced, activities prior and subsequent to occupants first becoming aware that something was wrong, perceived personal risk, time taken to respond and the inter-relationships between them. The results indicate differences in occupant activities across the floor clusters and suggest that these differences can be explained in terms of the perception of risk and the nature and extent of cues received by the participants.

Kinematics and EMG analysis of expert pole vaulter's lower limb during take off phase (P218)

Introduction: The critical phase, in jumping events in track and field, appears to be between touchdown and take-off. Since obvious similarities exist between the take off phase in both long jump and pole vault, numerous 3D kinematics and electromyographic studies have only looked at long jump. Currently there are few detailed kinematics electromyographic data on the pole vault take-off phase. The aim of this study was therefore to characterise kinematics and electromyographic variables during the take-off phase to provide a better understanding of this phase in pole vaulting and its role in performance outcome. Material and methods: Six pole-vaulters took part in the study. Kinematics data were captured with retro reflective markers fixed on the body. Hip, knee and ankle angle were calculated. Differential bipolar surface electrodes were placed on the following muscles of the take-off leg: tibialis anterior, lateral gastrocnemius, vastus lateralis, rectus femoris, bicep femoris and gluteus maximus. EMG activity was synchronously acquired with the kinematic data. EMG data were rectified and smoothed using a second order low pass Butterworth Bidirectional filter (resulting in a 4th order filter) with a cut-off frequency of 14 Hz. Results: Evolution of hip, knee and ankle angle show no significant differences during the last step before touchdown, the take-off phase and the beginning of fly phase. Meanwhile, strong differences in EMG signal are noted inter and intra pole vaulter. However for a same subject the EMG activities seem to converge to some phase locked point. Discussion: All pole vaulters have approximately the same visible coordination This coordination reflects a different muscular control among pole vaulters but also for a considered pole vaulter. These phase locked point could be considered as invariant of motor control i.e. a prerequisite for a normal sequence of the movement and performance realization.

Flexible diel vertical migration behaviour of zooplankton in the Irish Sea

The diel vertical migration (DVM) of the whole plankton community was investigated in the central and coastal Irish Sea. Generally, more than 60% of the plankton did not perform significant DVM. A correlation analysis of the weighted mean depths of different organisms and their potential predators suggested relationships between two groups, Oithona spp., copepod nauplii and fish larvae, and between Pseudocalanus elongatus, Calanus spp. and chaetognaths. The organisms showing significant DVM were chaetognaths (Sagitta spp.), Calanus spp. and P. elongatus. Calanus spp. showed clear ontogenic variations in DVM, and along with P. elongatus demonstrated great flexibility both in the amplitude and direction of migration. P. elongatus did not migrate in the coastal area and Calanus spp. showed a clear reverse migration. The direction of migration appeared to be related to the vertical position of the chaetognaths in the water column during the day.

Can the subtropical North Atlantic permanent thermocline be observed from space?

The analysis of remotely sensed altimeter data and in situ measurements shows that ERS 2 radar can monitor the ocean permanent thermocline from space. The remotely sensed sea level anomaly data account for similar to 2/3 of the temperature variance or vertical displacement of isotherms at a depth of similar to 550 m in the Subtropical North Atlantic Ocean near 32.5 degree N. This depth corresponds closely to the region of maximum temperature gradient in the permanent thermocline where near semi-annual internal vertical displacements reach 200 to 300 m. The gradient of the altimeter sea level anomaly data correlates well with measured ocean currents to a depth of 750 m. It is shown that observations from space can account for similar to 3/4 of the variance of ocean currents measured in situ in the permanent thermocline over a 2-y period. The magnification of the permanent thermocline displacement with respect to the displacement of the sea surface was determined as - x650 and gives a measure of the ratio of barotropic to baroclinic decay scale of geostrophic current with depth. The overall results are used to interpret an eight year altimeter data tie series in the Subtropical North Atlantic at 32.5 degree N which shows a dominant wave or eddy period near 200 days, rather than semi-annual and increases in energy propagating westward in 1995 (west of 25 degree W). The effects of rapid North Atlantic Oscillation climate change on ocean circulation are discussed. The altimeter data for the Atlantic were Fourier analysed. It is shown how the annual and semi-annual components relate to the seasonal maximum cholorophyll-a SeaWiFS signal in tropical and equatorial regions due to the lifting of the thermocline caused by seasonally varying ocean currents forced by wind stress.

Population-Growth And Vertical-Distribution Of Calanus-Helgolandicus In The Celtic Sea

Calanus helgolandicus over-winters in the shallow waters (100 m) of the Celtic Sea as copepodite stages V and VI; the minimum temperature in winter is approximately 8.0°C. This over-wintering is not a true hibernation or dormacy, accompanied by a reduced metabolic state with a discontinuation of feeding and development, but more of a lowered activity, involving reduced feeding and development, with predation on available microzooplankton and detritus. Analysis of specimens from the winter population showed that copepodite stages V and VI were actively feeding and still producing and possibly liberating eggs. The absence of late nauplii and young copepodites in the water column until late March indicated that there must be a high mortality of these winter cohorts. The copepodites of the first generation appeared in April–May, the younger stages, copepodites I to III, being distributed deeper in the water column below the euphotic zone and thermocline. This distribution would contribute to amuch slower rate of development. By August the ontogenetic vertical distributions observed in the copepodites were reversed, the younger stages occuring in the warmer surface layers within the euphotic zone. Diurnal migrations were observed in the later copepodites only, the younger stages I to III either remaining deep in spring or shallow in summer. The causal mechanisms which alter the behaviour of the young copepodites remain unexplained. The development of the population of Calanus helgolandicus in 1978, reaching its peak of abundance in August, was typical for the shelf seas around U.K. as observed from Continuous Plankton Recorder data, 1958 to 1977.

Development and validation of a shipboard system for measuring high-resolution vertical profiles of aqueous dimethylsulfide concentrations using chemical ionization mass spectrometry

A sampling and analytical system has been developed for shipboard measurements of high-resolution vertical profiles of the marine trace gas dimethylsulfide (DMS). The system consists of a tube attached to a CTD with a peristaltic pump on deck that delivers seawater to a membrane equilibrator and atmospheric pressure chemical ionization mass spectrometer (Eq-APCIMS). This allows profiling DMS concentrations to a depth of 50 m, with a depth resolution of 1.3-2 m and a detection limit of nearly 0.1 nmol L-1. The seawater is also plumbed to allow parallel operation of additional continuous instruments, and simultaneous collection of discrete samples for complementary analyses. A valve alternates delivery of seawater from the vertical profiler and the ship�s underway intake, thereby providing high-resolution measurements in both the vertical and horizontal dimensions. Tests conducted on various cruises in the Mediterranean Sea, Atlantic, Indian, and Pacific Oceans show good agreement between the Eq-APCIMS measurements and purge and trap gas chromatography with flame photometric detection (GC-FPD) and demonstrate that the delivery of seawater from the underway pump did not significantly affect endogenous DMS concentrations. Combination of the continuous flow DMS analysis with high-frequency hydrographic, optical, biological and meteorological measurements will greatly improve the spatial/temporal resolution of seagoing measurements and improve our understanding of DMS cycling.

Lateral diffusivity coefficients from the dynamics of a SF6 patch in a coastal environment

The dispersion of a patch of the tracer sulfur hexafluoride (SF6) is used to assess the lateral diffusivity in the coastal waters of the western part of the Gulf of Lion (GoL), northwestern Mediterranean Sea, during the Latex10 experiment (September 2010). Immediately after the release, the spreading of the patch is associated with a strong decrease of the SF6 concentrations due to the gas exchange from the ocean to the atmosphere. This has been accurately quantified, evidencing the impact of the strong wind conditions during the first days of this campaign. Few days after the release, as the atmospheric loss of SF6 decreased, lateral diffusivity coefficient at spatial scales of 10 km has been computed using two approaches. First, the evolution of the patch with time was combined with a diffusion-strain model to obtain estimates of the strain rate (γ = 2.5 10- 6 s- 1) and of the lateral diffusivity coefficient (Kh = 23.2 m2s− 1). Second, a steady state model was applied, showing Kh values similar to the previous method after a period of adjustment between 2 and 4.5 days. This implies that after such period, our computation of Kh becomes insensitive to the inclusion of further straining of the patch. Analysis of sea surface temperature satellite imagery shows the presence of a strong front in the study area. The front clearly affected the dynamics within the region and thus the temporal evolution of the patch. Our results are consistent with previous studies in open ocean and demonstrate the success and feasibility of those methods also under small-scale, rapidly-evolving dynamics typical of coastal environments.