Near Infrared (NIr) Light Increases Expression of a Marker of Mitochondrial Function in the Mouse Vestibular Sensory Epithelium

Strategies for attenuating decline in balance function with increasing age are predominantly focused on physical therapies including balance tasks and ...

University of Sydney

In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]).

Cost-utility analysis of survival with epoetin-alfa versus placebo in stage IV breast cancer.

The effectiveness of five temperature control algorithms for dual control volume grand canonical molecular dynamics is investigated in the study of hydrogen atom diffusion in a palladium bulk. The five algorithms, namely, Gaussian, generalized Gaussian moment thermostat (GGMT), velocity scaling, Nosé-Hoover (NH), and its enhanced version Nosé-Hoover chain (NHC) are examined in both equilibrium and nonequilibrium simulation studies. Our numerical results show that Gaussian yields the most inaccurate solutions for the hydrogen-palladium system due to the high friction coefficient generated from the large velocity fluctuation of hydrogen, while NHC, NH, and GGMT produce the most accurate temperature and density profiles in both equilibrium and nonequilibrium cases with their feedback control mechanisms. However, this feedback control also overestimates the self-diffusion coefficients in equilibrium systems and the diffusion coefficient in nonequilibrium systems. Velocity scaling thermostat produces slight inhomogeneities in the temperature and density profiles, but due to the dissipated heat accumulated in the control volumes it still yields accurate self-diffusion coefficients that are in good agreement with the experimental data at a wide range of temperatures while others tend to deviate.

Temperature control algorithms in dual control volume grand canonical molecular dynamics simulations of hydrogen diffusion in palladium.

Clinical studies show that the left atrial appendage, a blind-ended structure that is attached to the left atrium, may be the cause of 90% of atrial thrombi in atrial fibrillation (abnormal heart rhythm), and it is much reduced in sinus (normal) rhythm. In this paper, the effects of blood flows in left atrium and left atrial appendage are studied to help characterize the atrial appendage functions in sinus rhythm and atrial fibrillation using mathematical models. Our results show that the left atrial appendage is not functional in sinus rhythm because the atrial transmitral velocities remained almost identical for atria with and without appendage, which agrees with the current clinical observations. However, in atrial fibrillation, a proper atrial contraction is absent, which causes the second emptying velocity (A-wave) to be missing in both transmitral velocity and appendage filling/emptying velocity. Without the proper emptying of the blood, vortices generated in the chamber remain high strengths and with longer durations. They induce ineffective emptying of the blood in the atrium and appendage, which then lead to blood stagnation and subsequent thrombus formation.

Characterizing left atrial appendage functions in sinus rhythm and atrial fibrillation using computational models.

In this paper, nanoscale wetting on groove-patterned surfaces is thoroughly studied using molecular dynamics simulations. The results are compared with Wenzel's and Cassie's predictions to determine whether these continuum theories are still valid at the nanoscale for both hydrophobic and hydrophilic types of surfaces when the droplet size is comparable to the groove size. A system with a liquid mercury droplet and grooved copper substrate is simulated. The wetting properties are determined by measuring contact angles of the liquid droplet at equilibrium states. Correlations are established between the contact angle, roughness factor r, and surface fraction f. The results show that, for hydrophobic surfaces, the contact angle as a function of roughness factor and surface fraction on nanogrooved surfaces obeys the predictions from Wenzel's theory for wetted contacts and Cassie's theory for composite contacts. However, slight deviations occur in composite contacts when a small amount of liquid penetration is observed. The contact angle of this partial wetting cannot be accurately predicted using either Cassie's or Wenzel's theories. For hydrophilic surfaces, only wetted contacts are observed. In most cases, the resulting contact angles are found to be higher than Wenzel's predictions. At the nanoscale, high surface edge density plays an important role, which results in contact line pinning near plateau edges. For both hydrophobic and hydrophilic surfaces, substantial amount of anistropic spreading is found in the direction that is parallel to the grooves, especially at wetted or partially wetted contacts.

Nanoscale wetting on groove-patterned surfaces.

This paper summarizes the newly developed immersed finite element method (IFEM) and its applications to the modeling of biological systems. This work was inspired by the pioneering work of Professor T.J.R. Hughes in solving fluid-structure interaction problems. In IFEM, a Lagrangian solid mesh moves on top of a background Eulerian fluid mesh which spans the entire computational domain. Hence, mesh generation is greatly simplified. Moreover, both fluid and solid domains are modeled with the finite element method and the continuity between the fluid and solid subdomains is enforced via the interpolation of the velocities and the distribution of the forces with the reproducing Kernel particle method (RKPM) delta function. The proposed method is used to study the fluid-structure interaction problems encountered in human cardiovascular systems. Currently, the heart modeling is being constructed and the deployment process of an angioplasty stent has been simulated. Some preliminary results on monocyte and platelet deposition are presented. Blood rheology, in particular, the shear-rate dependent de-aggregation of red blood cell (RBC) clusters and the transport of deformable cells, are modeled. Furthermore, IFEM is combined with electrokinetics to study the mechanisms of nano/bio filament assembly for the understanding of cell motility.

Immersed finite element method and its applications to biological systems.

To biochemically characterize peripheral nerve amyloid in subjects with transthyretin (TTR) amyloidosis and assess effect of orthotopic liver transplantation (OLT) on progression of neuropathy.

Progression of transthyretin amyloid neuropathy after liver transplantation.

This study investigates shear-induced liquid structure changes in nanoscale Couette flows and their corresponding flow boundary conditions. Molecular dynamics simulations are used to model a liquid argon slab confined between two smooth rigid copper walls with an applied velocity at the upper wall to generate a planar Couette flow. Depending on the applied wall velocity, different liquid structures or the orderings of the liquid at liquid-solid interfaces are identified when reaching steady states. We define three regimes based on the ordering of the liquid structure: Newtonian, layer, and oversheared. Each regime is characterized by the spatial probability distribution and structure factor. These liquid structures are strongly correlated with the liquid velocity and density profiles in the flow. Ultimately, the liquid structures also determine the boundary conditions from pure slip to multilayer locking at liquid-solid interfaces. Our results show that temperature and liquid-solid interaction parameter are also important factors in influencing the liquid structures formed near interfaces.

Investigating liquid-solid interfacial phenomena in a Couette flow at nanoscale.

NK-cell leukemia is a clonal expansion of NK cells. The illness can occur in an aggressive or chronic form. We studied cell lines from human and rat NK-cell leukemias (aggressive NK-cell leukemia) as well as samples from patients with chronic NK-cell leukemia to investigate pathogenic mechanisms. Here we report that Mcl-1 was overexpressed in leukemic NK cells and that knockdown of Mcl-1 induced apoptosis in these leukemic cells. In vitro treatment of human and rat NK leukemia cells with FTY720 led to caspase-dependent apoptosis and decreased Mcl-1 expression in a time- and-dose-dependent manner. These biologic effects could be inhibited by blockade of reactive oxygen species generation and the lysosomal degradation pathway. Lipidomic analyses after FTY720 treatment demonstrated elevated levels of sphingosine, which mediated apoptosis of leukemic NK cells in vitro. Importantly, systemic administration of FTY720 induced complete remission in the syngeneic Fischer rat model of NK-cell leukemia. Therapeutic efficacy was associated with decreased expression of Mcl-1 in vivo. These data demonstrate that therapeutic benefit of FTY720 may result from both altered sphingolipid metabolism as well as enhanced degradation of a key component of survival signaling.

Therapeutic efficacy of FTY720 in a rat model of NK-cell leukemia.

Cancer invasion and metastasis are characterized by epithelial-mesenchymal transition (EMT). Hepatocellular carcinoma (HCC) causes metastasis and significant mortality. Elucidating factors promoting EMT in HCC are necessary to develop effective therapeutic strategies.

Cyclooxygenase-2 and Akt mediate multiple growth-factor-induced epithelial-mesenchymal transition in human hepatocellular carcinoma.

Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.

Targeted delivery of chemotherapy agents using a liver cancer-specific aptamer.

In this study, we use two nonequilibrium molecular dynamics algorithms, boundary-driven shear and homogeneous shear, to explore the rheology and flow properties of a simple fluid undergoing steady simple shear. The two distinct algorithms are designed to elucidate the influences of nanoscale confinement. The results of rheological material functions, i.e., viscosity and normal pressure differences, show consistent Newtonian behaviors at low shear rates from both systems. The comparison validates that confinements of the order of 10 nm are not strong enough to deviate the simple fluid behaviors from the continuum hydrodynamics. The non-Newtonian phenomena of the simple fluid are further investigated by the homogeneous shear simulations with much higher shear rates. We observe the "string phase" at high shear rates by applying both profile-biased and profile-unbiased thermostats. Contrary to other findings where the string phase is found to be an artifact of the thermostats, we perform a thorough analysis of the fluid microstructures formed due to shear, which shows that it is possible to have a string phase and second shear thinning for dense simple fluids.

Nanoscale simple-fluid behavior under steady shear.

The thermostats in molecular dynamics (MD) simulations of highly confined channel flow may have significant influences on the fidelity of transport phenomena. In this study, we exploit non-equilibrium MD simulations to generate Couette flows with different combinations of thermostat algorithms and strategies. We provide a comprehensive analysis on the effectiveness of three thermostat algorithms Nosé-Hoover chain (NHC), Langevin (LGV) and dissipative particle dynamics (DPD) when applied in three thermostat strategies, thermostating either walls (TW) or fluid (TF), and thermostating both the wall and fluid (TWTF). Our results of thermal and mechanical properties show that the TW strategy more closely resembles experimental conditions. The TF and TWTF systems also produce considerably similar behaviors in weakly sheared systems, but deviate the dynamics in strongly sheared systems due to the isothermal condition. The LGV and DPD thermostats used in the TF and TWTF systems provide vital ways to yield correct dynamics in coarse-grained systems by tuning the fluid transport coefficients. Using conventional NHC thermostat to thermostat fluid only produces correct thermal behaviors in weakly sheared systems, and breaks down due to significant thermal inhomogeneity in strongly sheared systems.

Thermostats and thermostat strategies for molecular dynamics simulations of nanofluidics.

Using molecular dynamics (MD), we investigate the importance of liquid-vapor interface topography in designing low-friction nanoengineered superhydrophobic surfaces. Shear flow is simulated on patterned surfaces. The relationship between the effective slip length and bubble meniscus curvature is attained by generating entrapped bubbles with large protrusion angles on patterned surfaces with nanoholes. We show that protruding bubbles can induce significant friction, which hinders the slip characteristics produced on liquid-vapor interfaces. By comparing surfaces with nanoholes and nanopillars, we also demonstrate that the continuity of the liquid-vapor interface can greatly influence slip. Our MD results yield an asymptotic behavior of slip length with varying gas fractions, which are found to be consistent with observations from simulations and analytical models produced in continuum studies.

Toward generating low-friction nanoengineered surfaces with liquid-vapor interfaces.

In this paper, we develop a "modified" immersed finite element method (mIFEM), a non-boundary-fitted numerical technique, to study fluid-structure interactions. Using this method, we can more precisely capture the solid dynamics by solving the solid governing equation instead of imposing it based on the fluid velocity field as in the original immersed finite element (IFEM). Using the IFEM may lead to severe solid mesh distortion because the solid deformation is been over-estimated, especially for high Reynolds number flows. In the mIFEM, the solid dynamics is solved using appropriate boundary conditions generated from the surrounding fluid, therefore produces more accurate and realistic coupled solutions. We show several 2-D and 3-D testing cases where the mIFEM has a noticeable advantage in handling complicated fluid-structure interactions when the solid behavior dominates the fluid flow.

Modified Immersed Finite Element Method For Fully-Coupled Fluid-Structure Interations.

Since the early 1920s there has been an interest in using bacteriophages (phages) for the control of bacterial pathogens. While there are many factors that have limited the success of phage bio-control, one particular problem is the variability of outcomes between phages and bacteria. Specifically, there is a significant need for a better understanding of how initial phage concentrations affect long-term bacterial inhibition. In work reported herein three phages were isolated for Escherichia coli K12, Pseudomonas aeruginosa PAO1, as well as Bacillus cereus and bio-control experiments were performed with phage concentrations ranging from 10(5) to 10(8) plaque forming units per mL over the course of 72 h. For four of the nine phages isolated there was a linear relationship between inhibition and phage concentration, suggesting the effect of phage concentration is important at longer time scales. For three of the isolated phages, phage concentrations had no effect on bacterial inhibition suggesting that even at the lowest concentration the method of action was saturated and lower concentrations might still be effective. Additionally, a cocktail was created and was compared to the previously isolated phages. There was no statistical difference between the cocktail and the best performing phage highlighting the importance of selecting the appropriate phages for treatment. These results suggest that, for certain phages, there is a strong relationship between phage concentration and long-term bacterial growth inhibition and the initial phage concentration is an important indicator of the long-term outcome.

Lucy Zhang

Discipline of Physiology

University of Sydney

Near Infrared (NIr) Light Increases Expression of a Marker of Mitochondrial Function in the Mouse Vestibular Sensory Epithelium

Lucy Zhang

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Discipline of Physiology

University of Sydney

Near Infrared (NIr) Light Increases Expression of a Marker of Mitochondrial Function in the Mouse Vestibular Sensory Epithelium

Discipline of Physiology