PET Imaging of Soluble Yttrium-86-Labeled Carbon Nanotubes in Mice

The potential medical applications of nanomaterials are shaping the landscape of the nanobiotechnology field and driving it forward. A key factor in determining the suitability of these nanomaterials must be how they interface with biological systems. Single walled carbon nanotubes (CNT) are being investigated as platforms for the delivery of biological, radiological, and chemical payloads to target tissues. CNT are mechanically robust graphene cylinders comprised of sp(2)-bonded carbon atoms and possessing highly regular structures with defined periodicity. CNT exhibit unique mechanochemical properties that can be exploited for the development of novel drug delivery platforms. In order to evaluate the potential usefulness of this CNT scaffold, we undertook an imaging study to determine the tissue biodistribution and pharmacokinetics of prototypical DOTA-functionalized CNT labeled with yttrium-86 and indium-111 ((86)Y-CNT and (111)In-CNT, respectively) in a mouse model.The (86)Y-CNT construct was synthesized from amine-functionalized, water-soluble CNT by covalently attaching multiple copies of DOTA chelates and then radiolabeling with the positron-emitting metal-ion, yttrium-86. A gamma-emitting (111)In-CNT construct was similarly prepared and purified. The constructs were characterized spectroscopically, microscopically, and chromatographically. The whole-body distribution and clearance of yttrium-86 was characterized at 3 and 24 hours post-injection using positron emission tomography (PET). The yttrium-86 cleared the blood within 3 hours and distributed predominantly to the kidneys, liver, spleen and bone. Although the activity that accumulated in the kidney cleared with time, the whole-body clearance was slow. Differential uptake in these target tissues was observed following intravenous or intraperitoneal injection.The whole-body PET images indicated that the major sites of accumulation of activity resulting from the administration of (86)Y-CNT were the kidney, liver, spleen, and to a much less extent the bone. Blood clearance was rapid and could be beneficial in the use of short-lived radionuclides in diagnostic applications

Towards reconciling structure and function in the nuclear pore complex

The spatial separation between the cytoplasm and the cell nucleus necessitates the continuous exchange of macromolecular cargo across the double-membraned nuclear envelope. Being the only passageway in and out of the nucleus, the nuclear pore complex (NPC) has the principal function of regulating the high throughput of nucleocytoplasmic transport in a highly selective manner so as to maintain cellular order and function. Here, we present a retrospective review of the evidence that has led to the current understanding of both NPC structure and function. Looking towards the future, we contemplate on how various outstanding effects and nanoscopic characteristics ought to be addressed, with the goal of reconciling structure and function into a single unified picture of the NPC

Determinants of Leukocyte Margination in Rectangular Microchannels

Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To determine the applicability of PDMS microchannels for blood flow analysis, we studied white blood cell (WBC) margination in channels of various geometries and blood compositions. We found that WBCs prefer to marginate downstream of sudden expansions, and that red blood cell (RBC) aggregation facilitates the process. In contrast to tubes, WBC margination was restricted to the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and consequently, margination efficiencies of more than 95% were achieved in a variety of channel geometries. In these pseudo-2D channels blood rheology and cell integrity were preserved over a range of flow rates, with the upper range limited by the shear in the vertical direction. We conclude that, with certain limitations, rectangular PDMS microfluidic channels are useful tools for quantitative studies of blood rheology

Earnings versus capital ratios management: role of bank types and SFAS 114

Banks, Earnings management, Capital management, Bank size, Bank risk, C21, G21, G28, M41, M48,

Far-Field Modeling of a Deep-Sea Blowout: Sensitivity Studies of Initial Conditions, Biodegradation, Sedimentation, and Subsurface Dispersant Injection on Surface Slicks and Oil Plume Concentrations

Modeling of large-scale oil transport and fate resulting from deep-sea oil spills is highly complex due to a number of bio-chemo-geophysical interactions, which are often empirically based. Predicting mass-conserved total petroleum hydrocarbon concentrations is thus still a challenge for most oil spill models. In addition, dynamic quantification and visualization of spilled oil concentrations are necessary both for first response and basin-wide impact studies. This chapter presents a new implementation of the Connectivity Modeling System (CMS) oil application that tracks individual multi-fraction oil droplets and estimates oil concentrations and oil mass in a 3D space grid. We used the Deepwater Horizon (DWH) blowout as a case study and performed a sensitivity analysis of several modeling key factors, such as biodegradation, sedimentation, and alternative initial conditions, including droplet size distribution (DSD) corresponding to an untreated and treated live oil from subsurface dispersant injection (SSDI) predicted experimentally under high pressure and by the VDROP-J jet-droplet formation model. This quantitative analysis enabled the reconstruction of a time evolving three-dimensional (3D) oil plume in the ocean interior, the rising and spreading of oil on the ocean surface, and the effect of SSDI in shifting the oil to deeper waters while conserving the mass balance. Our modeling framework and analyses are thus important technical advances for understanding and mitigating deep-sea blowouts