Microfluidic Preparation of Polymer-Nucleic Acid Nanocomplexes Improves Nonviral Gene Transfer

As the designs of polymer systems used to deliver nucleic acids continue to evolve, it is becoming increasingly apparent that the basic bulk manufacturing techniques of the past will be insufficient to produce polymer-nucleic acid nanocomplexes that possess the uniformity, stability, and potency required for their successful clinical translation and widespread commercialization. Traditional bulk-prepared products are often physicochemically heterogeneous and may vary significantly from one batch to the next. Here we show that preparation of bioreducible nanocomplexes with an emulsion-based droplet microfluidic system produces significantly improved nanoparticles that are up to fifty percent smaller, more uniform, and are less prone to aggregation. The intracellular integrity of nanocomplexes prepared with this microfluidic method is significantly prolonged, as detected using a high-throughput flow cytometric quantum dot Förster resonance energy transfer nanosensor system. These physical attributes conspire to consistently enhance the delivery of both plasmid DNA and messenger RNA payloads in stem cells, primary cells, and human cell lines. Innovation in processing is necessary to move the field toward the broader clinical implementation of safe and effective nonviral nucleic acid therapeutics, and preparation with droplet microfluidics represents a step forward in addressing the critical barrier of robust and reproducible nanocomplex productio

Effects of crossed states on photoluminescence excitation spectroscopy of InAs quantum dots

In this report, the influence of the intrinsic transitions between bound-to-delocalized states (crossed states or quasicontinuous density of electron-hole states) on photoluminescence excitation (PLE) spectra of InAs quantum dots (QDs) was investigated. The InAs QDs were different in size, shape, and number of bound states. Results from the PLE spectroscopy at low temperature and under a high magnetic field (up to 14 T) were compared. Our findings show that the profile of the PLE resonances associated with the bound transitions disintegrated and broadened. This was attributed to the coupling of the localized QD excited states to the crossed states and scattering of longitudinal acoustical (LA) phonons. The degree of spectral linewidth broadening was larger for the excited state in smaller QDs because of the higher crossed joint density of states and scattering rate

Effective conductivity of composites of graded spherical particles

We have employed the first-principles approach to compute the effective response of composites of graded spherical particles of arbitrary conductivity profiles. We solve the boundary-value problem for the polarizability of the graded particles and obtain the dipole moment as well as the multipole moments. We provide a rigorous proof of an {\em ad hoc} approximate method based on the differential effective multipole moment approximation (DEMMA) in which the differential effective dipole approximation (DEDA) is a special case. The method will be applied to an exactly solvable graded profile. We show that DEDA and DEMMA are indeed exact for graded spherical particles.Comment: submitted for publication

STATISTICAL METHODS FOR THE ANALYSIS OF CANCER GENOME SEQUENCING DATA

The purpose of cancer genome sequencing studies is to determine the nature and types of alterations present in a typical cancer and to discover genes mutated at high frequencies. In this article we discuss statistical methods for the analysis of data generated in these studies. We place special emphasis on a two-stage study design introduced by Sjoblom et al.[1]. In this context, we describe statistical methods for constructing scores that can be used to prioritize candidate genes for further investigation and to assess the statistical signicance of the candidates thus identfied

A Price Worth Paying: The Case for Controlling Marine Emissions in the Pearl River Delta

The Pearl River Delta (PRD) is a region with a single airshed, but different administrative and legal practices for controlling air quality. Under the Regional Cooperation Plan on Building a Quality Living Area (QLA Plan) released in June 2012 the Governments of Hong Kong, Guangdong and Macau have outlined a strategy to collaborate in reducing emissions from vessels throughout the PRD. This report provides evidence designed to assist policymakers in the region with this objective. It focuses on regulating toxic exhaust emissions from ocean-going vessels (OGVs) -- the most significant contributors of marine emissions. The findings show that marine sources of sulphur dioxide (SO2) emissions currently account for 519 premature deaths per annum in the PRD. These deaths could be reduced by 91% should an Emission Control Area (ECA) mandating the use of fuels with lower sulphur content be introduced. The report also demonstrates that three less comprehensive control measures would also reduce OGV emissions and associated public health impacts by 41-62%. Policymakers are encouraged to introduce these measures as stepping-stones on the way to establishment of an ECA for the PRD

Pseudogap and precursor superconductivity in underdoped cuprate high temperature superconductors: A far-infrared ellipsometry study

Abstract.: With the technique of infrared ellipsometry we performed a detailed study of the temperature- and doping dependence of the c-axis response of a series of YBa2Cu3O7−δ single crystals. In particular, we explored the anomalous electronic properties at temperatures above the macroscopic superconducting transition temperature, T c, whose conflicting explanations range from a precursor superconducting state to electronic correlations that compete with superconductivity. We show that the c-axis spectra provide evidence that both kinds of correlations are present and that their contributions can be disentangled based on an analysis with a so-called multilayer-model. We find that the onset temperature, T *, and the energy scale, ΔPG, of the competing pseudogap increase rapidly towards the underdoped side whereas they vanish on the overdoped side. In addition, we provide evidence that in a strongly underdoped sample the precursor superconducting correlations develop below an onset temperature, T ons, that is considerably lower than T * but still much higher than T

Vortices and dynamics in trapped Bose-Einstein condensates

I review the basic physics of ultracold dilute trapped atomic gases, with emphasis on Bose-Einstein condensation and quantized vortices. The hydrodynamic form of the Gross-Pitaevskii equation (a nonlinear Schr{\"o}dinger equation) illuminates the role of the density and the quantum-mechanical phase. One unique feature of these experimental systems is the opportunity to study the dynamics of vortices in real time, in contrast to typical experiments on superfluid $^4$He. I discuss three specific examples (precession of single vortices, motion of vortex dipoles, and Tkachenko oscillations of a vortex array). Other unusual features include the study of quantum turbulence and the behavior for rapid rotation, when the vortices form dense regular arrays. Ultimately, the system is predicted to make a quantum phase transition to various highly correlated many-body states (analogous to bosonic quantum Hall states) that are not superfluid and do not have condensate wave functions. At present, this transition remains elusive. Conceivably, laser-induced synthetic vector potentials can serve to reach this intriguing phase transition.Comment: Accepted for publication in Journal of Low Temperature Physics, conference proceedings: Symposia on Superfluids under Rotation (Lammi, Finland, April 2010

Some general properties of the renormalized stress-energy tensor for static quantum states on (n+1)-dimensional spherically symmetric black holes

We study the renormalized stress-energy tensor (RSET) for static quantum states on (n+1)-dimensional, static, spherically symmetric black holes. By solving the conservation equations, we are able to write the stress-energy tensor in terms of a single unknown function of the radial co-ordinate, plus two arbitrary constants. Conditions for the stress-energy tensor to be regular at event horizons (including the extremal and ``ultra-extremal'' cases) are then derived using generalized Kruskal-like co-ordinates. These results should be useful for future calculations of the RSET for static quantum states on spherically symmetric black hole geometries in any number of space-time dimensions.Comment: 9 pages, no figures, RevTeX4, references added, accepted for publication in General Relativity and Gravitatio