Electrophoresis of a polyelectrolyte through a nanopore

A hydrodynamic model for determining the electrophoretic speed of a polyelectrolyte through a nanopore is presented. It is assumed that the speed is determined by a balance of electrical and viscous forces arising from within the pore and that classical continuum electrostatics and hydrodynamics may be considered applicable. An explicit formula for the translocation speed as a function of the pore geometry and other physical parameters is obtained and is shown to be consistent with experimental measurements on DNA translocation through nanopores in silicon membranes. Experiments also show a weak dependence of the translocation speed on polymer length that is not accounted for by the present model. It is hypothesized that this is due to secondary effects that are neglected here.Comment: 5 pages, 2 column, 2 figure

Scalar Decay in Chaotic Mixing

I review the local theory of mixing, which focuses on infinitesimal blobs of scalar being advected and stretched by a random velocity field. An advantage of this theory is that it provides elegant analytical results. A disadvantage is that it is highly idealised. Nevertheless, it provides insight into the mechanism of chaotic mixing and the effect of random fluctuations on the rate of decay of the concentration field of a passive scalar.Comment: 35 pages, 15 figures. Springer-Verlag conference style svmult.cls (included). Published in "Transport in Geophysical Flows: Ten Years After," Proceedings of the Grand Combin Summer School, 14-24 June 2004, Valle d'Aosta, Italy. Fixed some typo

Effects of local hypothermia-rewarming on physiology, metabolism and inflammation of acutely injured human spinal cord.

In five patients with acute, severe thoracic traumatic spinal cord injuries (TSCIs), American spinal injuries association Impairment Scale (AIS) grades A-C, we induced cord hypothermia (33 °C) then rewarming (37 °C). A pressure probe and a microdialysis catheter were placed intradurally at the injury site to monitor intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue metabolism and inflammation. Cord hypothermia-rewarming, applied to awake patients, did not cause discomfort or neurological deterioration. Cooling did not affect cord physiology (ISP, SCPP), but markedly altered cord metabolism (increased glucose, lactate, lactate/pyruvate ratio (LPR), glutamate; decreased glycerol) and markedly reduced cord inflammation (reduced IL1β, IL8, MCP, MIP1α, MIP1β). Compared with pre-cooling baseline, rewarming was associated with significantly worse cord physiology (increased ICP, decreased SCPP), cord metabolism (increased lactate, LPR; decreased glucose, glycerol) and cord inflammation (increased IL1β, IL8, IL4, IL10, MCP, MIP1α). The study was terminated because three patients developed delayed wound infections. At 18-months, two patients improved and three stayed the same. We conclude that, after TSCI, hypothermia is potentially beneficial by reducing cord inflammation, though after rewarming these benefits are lost due to increases in cord swelling, ischemia and inflammation. We thus urge caution when using hypothermia-rewarming therapeutically in TSCI

Relative dispersion in fully developed turbulence: The Richardson's Law and Intermittency Corrections

Relative dispersion in fully developed turbulence is investigated by means of direct numerical simulations. Lagrangian statistics is found to be compatible with Richardson description although small systematic deviations are found. The value of the Richardson constant is estimated as $C_2 \simeq 0.55$, in a close agreement with recent experimental findings [S. Ott and J. Mann J. Fluid Mech. {\bf 422}, 207 (2000)]. By means of exit-time statistics it is shown that the deviations from Richardson's law are a consequence of Eulerian intermittency. The measured Lagrangian scaling exponents require a set of Eulerian structure function exponents $\zeta_{p}$ which are remarkably close to standard ones known for fully developed turbulence

Nested-Nanobubbles for Ultrasound Triggered Drug Release

Due to their size (1-10 μm) microbubble-based drug delivery agents suffer from confinement to the vasculature, limiting tumour penetration and potentially reducing drug efficacy. Nanobubbles (NBs) have emerged as promising candidates for ultrasound triggered drug delivery, due to their small size allowing drug delivery complexes to take advantage of the enhanced permeability and retention effect. In this study we describe a simple method for production of Nested-NBs, by encapsulation of NBs (~ 100 nm) within drug loaded liposomes. This method combines the efficient and well-established drug loading capabilities of liposomes, whilst utilizing NBs as an acoustic trigger for drug release. Encapsulation was characterized using Transmission Electron Microscopy with an encapsulation efficiency of 22 ± 2 %. Nested-NBs demonstrated echogenicity using diagnostic B-mode imaging and acoustic emissions were monitored during high intensity focused ultrasound (HIFU) in addition to monitoring of model drug release. Results showed that although the encapsulated NBs were destroyed by pulsed HIFU (peak negative pressure 1.54 – 4.83 MPa), signified by loss of echogenicity and detection of inertial cavitation, no model drug release was observed. Changing modality to continuous wave (CW) HIFU produced release across a range of peak negative pressures (2.01 – 3.90 MPa), likely due to a synergistic effect of mechanical and increased thermal stimuli. Due to this, we predict that our NBs contain a mixed population of both gaseous and liquid core particles, which upon CW HIFU undergo rapid phase conversion, triggering liposomal drug release. This hypothesis was investigated using previously described models to predict the existence of droplets and their phase change potential and the ability of this phase change to induce liposomal drug release

d=2, N=2 Superconformal Symmetries and Models

We discuss the following aspects of two-dimensional N=2 supersymmetric theories defined on compact super Riemann surfaces: parametrization of (2,0) and (2,2) superconformal structures in terms of Beltrami coefficients and formulation of superconformal models on such surfaces (invariant actions, anomalies and compensating actions, Ward identities).Comment: 43 pages, late

Localized induction equation and pseudospherical surfaces

We describe a close connection between the localized induction equation hierarchy of integrable evolution equations on space curves, and surfaces of constant negative Gauss curvature.Comment: 21 pages, AMSTeX file. To appear in Journal of Physics A: Mathematical and Genera

High-throughput microfluidics for evaluating microbubble enhanced delivery of cancer therapeutics in spheroid cultures

Drug penetration into solid tumours remains a major challenge in the effective treatment of cancer. Microbubble (MB) mediated sonoporation offers a potential solution to this by enhancing the uptake of drugs into cells. Additionally, in using an ultrasound (US) trigger, drug delivery can be localised to the tumour, thus reducing the off-site toxicity associated with systemic delivery. The majority of in vitro studies involving the observation of MB-enhanced drug efficacy have been conducted on 2D monolayer cell cultures, which are known to be poor models for in vivo tumours. 3D spheroid cultures allow for the production of multicellular cultures complete with extracellular matrix (ECM) components. These cultures effectively recreate many of the physiological features of the tumour microenvironment and have been shown to be far superior to previous 2D monolayer models. However, spheroids are typically handled in well-plates in which the fluid environment is static, limiting the physiological relevance of the model. The combination of 3D cultures and microfluidics would allow for the production of a dynamic system in which spheroids are subjected to in vivo like fluid flow and shear stressesThis study presents a microfluidic device containing an array of spheroid traps, into which multiple pre-grown colorectal cancer (CRC) spheroids were loaded. Reservoirs interfaced with the chip use hydrostatic pressure to passively drive flow through the system and subject spheroids to capillary like flow velocities. The use of reservoirs also enabled multiple chips to be run in parallel, allowing for the screening of multiple therapeutic treatments (n = 690 total spheroids analysed). This microfluidic platform was used to investigate MB enhanced drug delivery and showed that co-delivery of 3 μM doxorubicin (DOX) + MB + US reduced spheroid viability to 48 ± 2%, compared to 75 ± 5% observed with 3 μM DOX alone. Delivery of drug loaded MBs (DLMBs), in which DOX-loaded liposomes (DOX-LS) were conjugated to MBs, reduced spheroid viability to 62 ± 3%, a decrease compared to the 75 ± 3% viability observed with DOX-LS in the absence of MBs + US

Breakdown of Scale Invariance in the Phase Ordering of Fractal Clusters

Our numerical simulations with the Cahn-Hilliard equation show that coarsening of fractal clusters (FCs) is not a scale-invariant process. On the other hand, a typical coarsening length scale and interfacial area of the FC exhibit power laws in time, while the mass fractal dimension remains invariant. The initial value of the lower cutoff is a relevant length scale. A sharp-interface model is formulated that can follow the whole dynamics of a diffusion controlled growth, coarsening, fragmentation and approach to equilibrium in a system with conserved order parameter.Comment: 4 pages, 4 figures, RevTex, submitted to PR