Structural Properties of Thermoresponsive Poly(N-isopropylacrylamide)-poly(ethyleneglycol) Microgels

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising approach to siRNA carriers is dynamic versatile nanoparticles that can perform several in vivo functions. Over the last several years, our research group has investigated hydrogel nanoparticles (nanogels) as candidate delivery vehicles for therapeutics, including siRNA. Throughout the course of our research, we have developed higher order architectures composed entirely of hydrogel components, where several different hydrogel chemistries may be isolated in unique compartments of a single construct. In this Account, we summarize a subset of our experiences in the design and application of nanogels in the context of drug delivery, summarizing the relevant characteristics for these materials as delivery vehicles for siRNA. Through the layering of multiple, orthogonal chemistries in a nanogel structure, we can impart multiple functions to the materials. We consider nanogels as a platform technology, where each functional element of the particle may be independently tuned to optimize the particle for the desired application. For instance, we can modify the shell compartment of a vehicle for cell-specific targeting or evasion of the innate immune system, whereas other compartments may incorporate fluorescent probes or regulate the encapsulation and release of macromolecular therapeutics. Proof-of-principle experiments have demonstrated the utility of multifunctional nanogels. For example, using a simple core/shell nanogel architecture, we have recently reported the delivery of siRNA to chemosensitize drug resistant ovarian cancer cells. Ongoing efforts have resulted in several advanced hydrogel structures, including biodegradable nanogels and multicompartment spheres. In parallel, our research group has studied other properties of the nanogels, including their behavior in confined environments and their ability to translocate through small pores

Diffusive and Arrestedlike Dynamics in Currency Exchange Markets

This work studies the symmetry between colloidal dynamics and the dynamics of the Euro–U.S. dollar currency exchange market (EURUSD). We consider the EURUSD price in the time range between 2001 and 2015, where we find significant qualitative symmetry between fluctuation distributions from this market and the ones belonging to colloidal particles in supercooled or arrested states. In particular, we find that models used for arrested physical systems are suitable for describing the EURUSD fluctuation distributions. Whereas the corresponding mean-squared price displacement (MSPD) to the EURUSD is diffusive for all years, when focusing in selected time frames within a day, we find a two-step MSPD when the New York Stock Exchange market closes, comparable to the dynamics in supercooled systems. This is corroborated by looking at the price correlation functions and non-Gaussian parameters and can be described by the theoretical model. We discuss the origin and implications of this analogy

A model for foreign exchange markets based on glassy Brownian systems.

In this work we extend a well-known model from arrested physical systems, and employ it in order to efficiently depict different currency pairs of foreign exchange market price fluctuation distributions. We consider the exchange rate price in the time range between 2010 and 2016 at yearly time intervals and resolved at one minute frequency. We then fit the experimental datasets with this model, and find significant qualitative symmetry between price fluctuation distributions from the currency market, and the ones belonging to colloidal particles position in arrested states. The main contribution of this paper is a well-known physical model that does not necessarily assume the independent and identically distributed (i.i.d.) restrictive condition

Comparison of the experimental pdf vs iid one.

<p>Comparison of the experimental pdf (circle) vs iid one (triangles) for EURUSD in the year 2010 for a lag time of 10 minutes (left panel) and 30 minutes (right panel). The solid line is a Gaussian fit to the iid process.</p

Pdf of USDHKD.

<p>Pdf of USDHKD with lags 10, 30, 100 and 250 minutes for the year 2016.</p

Pdf of EURUSD.

<p>Pdf of EURUSD with lag times 10, 30, 100 and 250 minutes, for the year 2015.</p

Pdf of NZDSGD.

<p>Pdf of NZDSGD with lag times 10, 30, 100 and 250 minutes, for the year 2014.</p

Absolute moments.

<p>Absolute moments of order 0.1, 1, 2, 3, 4 (from top to bottom) of AUDCAD for the year 2010.</p