NUMERICAL INVESTIGATION OF INTERCEPTOR EFFECT ON SEA KEEPING BEHAVIOUR OF PLANING HULL ADVANCING IN REGULAR HEAD WAVES

In this paper an attempt has been made to assess the capability of numerical algorithm based on Reynolds Averaged Navier Stokes (RANS) for predicting the motion characteristics of the planing hull in calm water and regular waves. The focus of the present study is the impact of interceptors on the sea keeping quality of a planing vessel investigated through the application of numerical methods. The wave properties such as wavelength and wave height are taken into consideration to investigate the effect of wave steepness on vessel response. It is found that numerical data can efficiently simulate the motion attitude and the hydrodynamic characteristics of planing craft in regular head waves. The planing hull with and without interceptor fitted at the transom is simulated in numerical wave tank. The results show reduction in heave and pitch motions which gave favorable sea keeping behavior for the hull fitted with interceptor. The numerical solution is useful for the preliminary prediction of navigation safety during sailing.

Relation between pre-existing plaque size and neointimal healing in an adult porcine model of familial hypercholesterolemia

Background Despite the efficacy of novel drug eluting stents (DES) in preventing restenosis, this complication still occurs, as do neo-atherosclerosis development and poor stent strut coverage that are associated with stent thrombosis. Safety and efficacy of novel coronary stents are preclinically being tested using an established porcine coronary model. However, the use of young healthy animal only allow limited conclusions to be drawn on the long-term effects, as the artieries do not reflect human pathology of advanced atherosclerosis. A key unresolved question is whether and how the presence, size and composition of pre-existing atherosclerotic plaque affect neointimal healing. Purpose The objective of this study is to understand the role of atherosclerotic plaque in neointimal response following DES placement in a large animal model of coronary artery disease by using optical coherence tomography (OCT) analysis. Methods The study was approved by the animal ethics committee. Familial hypercholesterolemia (FH) swine (n=6 Bretoncelles-Meishan) were given a high fat diet for 12 months to develop atherosclerosis. Stents (n=14) were implanted in n=14 coronary arteries under guidance of OCT with a stent-artery ratio of 1.1:1 at sites of atherosclerotic plaque, and animals were sacrificed after 28 days. Two types of Sirolimus eluting stents with different release profiles were implanted. Serial OCT pullbacks were taken before and after stent placement and after 28 days (follow-up), quantitatively analyzed and compared using dedicated software. The lumen area, stent area, plaque size (calculated as external elastic lamina (EEL) area - lumen area) and neointima (calculated as stent area – lumen area) were evaluated for each frame and averaged per stent. The plaque burden before stent implantation was evaluated at the same site of stent placement using coronary side branches as reference. Results The graph shows the association between the pre-existing plaque size before stenting and neointima formation after 28 days. Surprisingly, more pre-existing plaque size resulted in less neointima (P<0.01). There was one outlier, a stent with long dissection and extensive malapposition at baseline which showed an excessive tissue response at follow-up. The response in this animal model shows similarity to human vessel response as both regions with thin neointima formation as well as poor strut coverage were observed for both stent types. Conclusion The novel model of adult FH swine shows long-term vessel response to DES, that is similar to human response. This work shows that pre-existing atherosclerotic plaque affects the neointima after DES implantation. This insight highlights the necessity to use relevant disease models for safety and efficacy testing. Plaque size and neointima relation Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organisation for Health Research and Development (ZonMw)

Grey-box linear modeling to analyze functional near-infrared spectroscopy-based cerebrovascular reactivity to anodal HD-tDCS in healthy humans

The mechanism of action for the cerebral vasculature hemodynamic response to the electric field effects during transcranial direct current stimulation (tDCS) has been less explored. We postulate that such a mechanistic understanding of the cerebrovascular reactivity (CVR) to tDCS can facilitate adequate tDCS dosing to facilitate cognitive rehabilitation in mild cognitive impairment and dementia as well as motor rehabilitation in stroke and traumatic brain injuries. This study presents a system identification approach to evaluate CVR under high-definition (HD) tDCS using a physiologically constrained model based on a multi-compartmental neurovascular system of vascular smooth muscle, perivascular space, synaptic space, and astrocyte glial cell. The physiologically detailed model generated vessel oscillations in the frequency range of 0.05 – 0.2 Hz driven by nonlinear calcium dynamics. Then, model linearization was performed to develop a grey-box linear model for evaluating the acute effects of HD-tDCS based on the CVR data from healthy humans. CVR was measured using functional near-infrared spectroscopy (fNIRS) with optodes in the vicinity of 4x1 HD-tDCS electrodes. The grey-box linear model response of vessel response through the synaptic potassium pathway was found comparable to known hemodynamic responses. Then, the grey-box linear model was fitted to the CVR to anodal HD-tDCS found from the normalized changes in the fNIRS-total haemoglobin (tHb) concentration (blood volume) in eleven healthy participants. We found that the model pathway from perivascular potassium to the vessel circumference presented the best fNIRS-tHb fit with the least mean square error. The fitted grey-box linear model response presented an initial dip in the vessel response that provided a mechanistic understanding of the fNIRS-tHb changes at the onset of HD-tDCS, which needs to be validated in the future with functional magnetic resonance imaging in conjunction with HD-tDCS.

A Novel Bi-Modal Wave Analysis Approach to Pipelay Installation Analysis

The single wave or uni-modal wave analysis approach to define the installation seastates, based on a single wave with varying directions, wave heights and periods, is a standard approach among the installation contractors. However, in many of the offshore projects, e.g. offshore Trinidad, and Senegal and Mauritania, bi-modal seatates or waves are a common occurrence, but they are not considered in the installation analysis due to the complexity of the analysis and the computation time required to capture two waves, i.e. wind-sea and swell concurrently from different directions. A novel bi-modal wave analysis approach is developed to assess the risk to pipelay installation operations due to the impact of bi-modal waves on the installation vessel, characterised by two peak frequencies of varying directions, wave heights and periods. The approach requires the use of clustered data, based on hindcast wave data over a period of time which can be provided by the Metocean Specialist. A combination of statistical evaluation of the clustered data and vessel response screening is used to identify critical clustered pairs for further installation analysis, and to complement the established single wave analysis and the associated installation seastates. An example is provided in this paper to illustrate the benefits of bi-modal waves consideration, and to demonstrate the use of this novel approach in order to ensure any potential risk is captured so that the pipelay installation operations can be carried out in a safe offshore environment.

4071 Dynamic Control of Tumor Vessels Augments Antitumor Responses

OBJECTIVES/GOALS: Our overall objective is to develop a directly observable and reproducible method of enhanced blood flow through tumor vessels (i.e. dynamic control) at the time of systemic treatment delivery. Our central hypothesis is that the dynamic control of tumor vessels will improve (1) systemic drug delivery and (2) effector cell trafficking to target tumor. METHODS/STUDY POPULATION: B16 melanoma cells were inoculated into C57BL/6 (B6) mice (male and female) in both regional (hind leg) and systemic (flank) models. Dynamic control consisted of an IV saline bolus (500 ul) and phenylephrine (10 ug). Tumor vessel response was observed in real-time through window chambers using intravital microscopy (IVM). Dynamic control was combined with melphalan (20 mg/ml) either regionally (isolated limb perfusion) or systemically. Outcomes included tumor growth, survival, IHC, and toxicity. Dynamic control will be combined with adoptive transfer of effector T cells. B6 mice will be inoculated with B16/OVA (flank with window chamber) and treated with fluorescently labeled (calcein), OVA-specific CD8+ T cells from OT-1 transgenic mice. IVM, IHC, and flow cytometry will be used to measure T cell trafficking. RESULTS/ANTICIPATED RESULTS: Dynamic control (1) restored blood flow in non-functional tumor vessels and (2) increased and then transiently reversed blood flow in functional vessels. Vessel diameters did not change, suggesting that shunting of systemic blood to the tumor vasculature accounted for the observed changes. Dynamic control augmented tumor responses in our regional therapy model of melanoma. Increases in DNA adduct formation (melphalan mechanism of action) detected by IHC, decreased tumor growth, and increased survival were observed with dynamic control. There was no increased limb toxicity. Similarly, dynamic control augmented responses in our systemic therapy model (decreased tumor growth and improved survival). We anticipate that dynamic control will improve trafficking of effector T cells in the next set of experiments. DISCUSSION/SIGNIFICANCE OF IMPACT: Heterogeneous responses to systemic therapies represent a major gap in current cancer treatment. An essential requirement for any effective therapy is its ability to reach tumor via the tumor-associated vasculature. We have therefore developed an approach to enhance drug delivery (dynamic control), which we also plan to test in clinical trials.

Seaworthiness Through Intelligent Trajectory Control

Navigation of autonomous surface vessels, less than 20 m in length, in large sea states is difficult and often precludes successful completion of the assigned mission or, in the worst case, survivability. Operation in high seas requires sensing of the local wave environment and determining a vessel trajectory that maximizes survivability based on knowledge of the vessel response functions and prediction of the incident wave field forward in time. To achieve this objective, new technologies are being developed and tested in full scale at the Marine Autonomy Research Site (MARS), located in central Lake Superior and operated by Michigan Technological University. In this initial set of experiments, a skilled human operator was used as a surrogate for an envisioned wave-adaptive autonomous control system. The test vehicle is a fully instrumented personal watercraft, operated by a U.S. Coast Guard-trained surf-boat operator in moderate sea states with Froude number (Fr) = 1.0 through a course consisting of up-wave, cross-wave, and down-wave legs. Results dramatically document that the wave-dodging maneuvers employed are designed to minimize vessel pitch (preserve propulsor and rudder control) while allowing increased vessel roll. Comparisons of the straight line with wave-dodging circuits during constant sea state conditions show that vehicle roll is at times twice greater in wave-dodging runs while vehicle pitch averages half to one third of that in the straight-line course. These data suggest that optimum paths do exist through steep, evolving incident wave fields and these optimum paths can produce significant improvements in vessel survivability.

Assessment of the Reliability of the Moorings of a Floating Structure Against the Extreme Cyclone Hazard

This paper describes the methodology adopted for an analysis performed to assess the reliability of the moorings of a free weathervaning FPSO against the cyclone hazard. A joint distribution characterizing the long-term cyclone metocean conditions was fitted to a database of environmental conditions at the site of interest. A series of archetype cyclone histories were selected from the cyclone database to capture the evolving relationships between key environmental parameters during a cyclone. A response-surface model for extreme tension in the vessel moorings was developed for the short-term extreme vessel response as a function of environmental conditions by fitting the surface to an extensive series of time-domain vessel response analyses. The reliability of the mooring system was evaluated using Monte Carlo simulation by sampling from the fitted joint distribution of long-term cyclone characteristic and generating simulated cyclone time histories by scaling the archetype cyclones. The response model for short-term exceedance probability is used to develop the probability of exceedance within each simulated cyclone, and the probability of exceeding a given response is derived from the simulation.