First Passage Time Densities in Non-Markovian Models with Subthreshold Oscillations

Motivated by the dynamics of resonant neurons we consider a differentiable, non-Markovian random process $x(t)$ and particularly the time after which it will reach a certain level $x_b$. The probability density of this first passage time is expressed as infinite series of integrals over joint probability densities of $x$ and its velocity $\dot{x}$. Approximating higher order terms of this series through the lower order ones leads to closed expressions in the cases of vanishing and moderate correlations between subsequent crossings of $x_b$. For a linear oscillator driven by white or coloured Gaussian noise, which models a resonant neuron, we show that these approximations reproduce the complex structures of the first passage time densities characteristic for the underdamped dynamics, where Markovian approximations (giving monotonous first passage time distribution) fail

High-Density Targeting of a Viral Multifunctional Nanoplatform to a Pathogenic, Biofilm-Forming Bacterium

SummaryNanomedicine directed at diagnosis and treatment of infections can benefit from innovations that have substantially increased the variety of available multifunctional nanoplatforms. Here, we targeted a spherical, icosahedral viral nanoplatform to a pathogenic, biofilm-forming bacterium, Staphylococcus aureus. Density of binding mediated through specific protein-ligand interactions exceeded the density expected for a planar, hexagonally close-packed array. A multifunctionalized viral protein cage was used to load imaging agents (fluorophore and MRI contrast agent) onto cells. The fluorescence-imaging capability allowed for direct observation of penetration of the nanoplatform into an S. aureus biofilm. These results demonstrate that multifunctional nanoplatforms based on protein cage architectures have significant potential as tools for both diagnosis and targeted treatment of recalcitrant bacterial infections

Ultrafast 3d spin-echo acquisition improves gadolinium-enhanced mri signal contrast enhancement

Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T 2 & z.ast; effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (??32) and compressed sensing (CS) sampling (??8) allowed highly-accelerated 3D Multiple-Modulation- Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (??7) over that of corresponding FLASH acquisitions (??2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution.open0

A Library of Protein Cage Architectures as Nanomaterials

Virus capsids and other structurally related cage-like proteins such as ferritins, dps, and heat shock proteins have three distinct surfaces (inside, outside, interface) that can be exploited to generate nanomaterials with multiple functionality by design. Protein cages are biological in origin and each cage exhibits extremely homogeneous size distribution. This homogeneity can be used to attain a high degree of homogeneity of the templated material and its associated property. A series of protein cages exhibiting diversity in size, functionality, and chemical and thermal stabilities can be utilized for materials synthesis under a variety of conditions. Since synthetic approaches to materials science often use harsh temperature and pH, it is an advantage to utilize protein cages from extreme environments. In this chapter, we review recent studies on discovering novel protein cages from harsh natural environments such as the acidic thermal hot springs at Yellowstone National Park (YNP) and on utilizing protein cages as nano-scale platforms for developing nanomaterials with wide range of applications from electronics to biomedicine.close433

Virus-like Particles Templated by DNA Micelles: A General Method for Loading Virus Nanocarriers\ud

DNA amphiphile particles template formation of virus capsids and enable their loading.