Magnetic Susceptibility: Further Insights into Macroscopic and Microscopic Fields and the Sphere of Lorentz

To make certain quantitative interpretations of spectra from NMR experiments carried out on heterogeneous samples, such as cells and tissues, we must be able to estimate the magnetic and electric fields experienced by the resonant nuclei of atoms in the sample. Here, we analyze the relationships between these fields and the fields obtained by solving the Maxwell equations that describe the bulk properties of the materials present. This analysis separates the contribution to these fields of the molecule in which the atom in question is bonded, the "host" fields, from the contribution of all the other molecules in the system, the "external" fields. We discuss the circumstances under which the latter can be found by determining the macroscopic fields in the sample and then removing the averaged contribution of the host molecule. We demonstrate that the results produced by the, so-called, "sphere of Lorentz" construction are of general validity in both static and time-varying cases. This analytic construct, however, is not "mystical" and its justification rests not on any sphericity in the system but on the local uniformity and isotropy, i.e., spherical symmetry, of the medium when averaged over random microscopic configurations. This local averaging is precisely that which defines the equations that describe the macroscopic fields. Hence, the external microscopic fields, in a suitably averaged sense, can be estimated from the macroscopic fields. We then discuss the calculation of the external fields and that of the resonant nucleus in NMR experiments.Comment: 21 pages, 8 figures, v2: updated to resemble the published versio

Multimodality imaging in vivo for preclinical assessment of tumor-targeted doxorubicin nanoparticles.

This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic

Adapting to a Design-Based Professional Learning Intervention

Designing a systematic inquiry-based, and knowledge-building experience through continuous professional learning for teachers is a key challenge for school authorities. A total of 26 teachers, five principals, three researchers, one graduate student, and two contract professionals from a university were involved in a research-practice partnership. The partners engaged in a yearlong design-based professional learning series. In this study, design-based research was used as the methodology to understand the participant responses to professional learning during the design, enactment, and refinement phases used to design the professional learning series. Open-ended survey responses, researcher field notes and documents from the professional learning sessions were analyzed throughout the study and during three phases of the learning design. The results indicated there were four key shifts and corresponding adaptations made by the participants as they responded to and engaged in a continuous model of professional learning

Learning curve analysis of thoracic endovascular aortic repair in relation to credentialing guidelines

ObjectiveRecently, practice guideline documents have recommended the completion of different levels of interventional experience and 5 or 10 thoracic endovascular aortic cases prior to surgeon credentialing. This study’s purpose was to determine whether these requirements are valid by reviewing three surgeons’ learning curves with thoracic aortic endovascular repairs.MethodsBetween 1998 and 2006, 67 patients underwent emergent or elective endovascular repair of thoracic aortic pathologies by one of three vascular surgeons with extensive experience with catheter manipulation and abdominal aortic endografts. Following standard retrospective review, each surgeon’s learning curve was analyzed using the cumulative sum failure method with a target success rate of 95% derived from the literature. The main outcome variable was primary technical success.ResultsThese 67 patients presented with several pathologies including elective (n = 31) and ruptured (n = 11) thoracic aortic aneurysms, acute dissections or aortic ulcers (n = 10), and acute blunt thoracic aortic trauma (n = 15). The mean age was 65 (range: 20 to 90) and the early (30 day) mortality rate was 19.4% in urgent cases (n = 36) and 0% in elective cases (n = 31). Paraplegia occurred in two patients (3%). Primary technical success was achieved in 62 cases (92.5%) and did not differ between surgeons (92.6%, 91.3%, 94.1%, respectively; P = .9). Each surgeon’s cases were plotted sequentially and the resulting learning curves were similar. Although acceptable outcomes were obtained throughout the study period, improved results, compared with the target success rate, were not achieved until each surgeon treated 5 to 10 patients.ConclusionThis study supports the case volume requirements of the Society for Vascular Surgery credentialing guidelines, which also requires extensive catheter and guidewire experience. With this background in catheter manipulation and endovascular abdominal aortic repair, surgeons can achieve optimal outcomes with thoracic aortic lesions following 5 to 10 cases

Magnetic Susceptibility: Solutions, Emulsions, and Cells

Differences in magnetic susceptibility between various compartments in heterogeneous samples can introduce unanticipated complications to NMR spectra. On the other hand, an understanding of these effects at the level of the underlying physical principles has led to the development of several experimental techniques that provide data on cellular function that are unique to NMR spectroscopy. To illustrate some key features of susceptibility effects we present, among a more general overview, results obtained with red blood cells and a recently described model system involving diethyl phthalate in water. This substance forms a relatively stable emulsion in water and yet it has a significant solubility of 5 mmol/L at room temperature; thus, the NMR spectrum has twice as many resonances as would be expected for a simple solution. What determines the relative intensities of the two families of peaks and can their frequencies be manipulated experimentally in a predictable way? The theory used to interpret the NMR spectra from the model system and cells was first developed in the context of electrostatics nearly a century ago, and yet some of its underlying assumptions now warrant closer scrutiny. While this insight is used in a practical way in this article, the accompanying article deals with the mathematics and physics behind this new analysis.Comment: 15 pages, 9 figures, v2: updated to resemble the published versio

Accelerating Bayesian hierarchical clustering of time series data with a randomised algorithm

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/

Development of a tomato xylem-mimicking microfluidic system to study Ralstonia pseudosolanacearum biofilm formation

The bacterial wilt pathogen Ralstonia pseudosolanacearum (Rps) colonizes plant xylem vessels and blocks the flow of xylem sap by its biofilm (comprising of bacterial cells and extracellular material), resulting in devastating wilt disease across many economically important host plants including tomatoes. The technical challenges of imaging the xylem environment, along with the use of artificial cell culture plates and media in existing in vitro systems, limit the understanding of Rps biofilm formation and its infection dynamics. In this study, we designed and built a microfluidic system that mimicked the physical and chemical conditions of the tomato xylem vessels, and allowed us to dissect Rps responses to different xylem-like conditions. The system, incorporating functional surface coatings of carboxymethyl cellulose-dopamine, provided a bioactive environment that significantly enhanced Rps attachment and biofilm formation in the presence of tomato xylem sap. Using computational approaches, we confirmed that Rps experienced linear increasing drag forces in xylem-mimicking channels at higher flow rates. Consistently, attachment and biofilm assays conducted in our microfluidic system revealed that both seeding time and flow rates were critical for bacterial adhesion to surface and biofilm formation inside the channels. These findings provided insights into the Rps attachment and biofilm formation processes, contributing to a better understanding of plant-pathogen interactions during wilt disease development

Time evolution of probability density function of gamma ray burst (GRB) - a possible indication of turbulence origin of GRB

Gamma ray burst (GRB) time series is a non-stationary time series with all its statistical properties varying with time. Considering that each GRB is a different manifestation of the same stochastic process we studied the time dependent as well as time averaged probability density function (\emph{pdf}) characterizing the underlying stochastic process. The \emph{pdf}s are fitted with Gaussian distribution function and it has been argued that the Gaussian \emph{pdf}s possibly indicate the turbulence origin of GRB. The spectral and temporal evolution of GRBs are also studied through the evolution of spectral forms, color-color diagrams and hysteresis loops. The results do not contradict the turbulence interpretation of GRB.Comment: Accepted for publication in MNRA

(β-D-ribofuranosyl)formamidine in the design and synthesis of 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives

A wide range of novel 2-(β-D-ribofuranosyl)pyrimidines, including RF-containing derivatives, have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with various dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl)propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Polyfluoroalkyl-containing 2-(β-D-ribofuranosyl)pyrimidine derivatives have been synthesized by the reaction of (β-D-ribofuranosyl)formamidine with dielectrophilic substrates such as 3-alkoxy- and 3-chloro-1-(polyfluoroalkyl) propen-1-ones, 3-nitro- and 3-(phenylethynyl)chromones and heteroaryl acetylenic ketones. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim