Cyclodextrin‐Based Bimodal Fluorescence/MRI Contrast Agents: An Efficient Approach to Cellular Imaging

A novel bimodal fluorescence/MRI probe based on a cyclodextrin scaffold has been synthesized and characterized. The final agent employs the fluorescein (F) functionality as a fluorescence marker and the Gd^III complex of a macrocyclic DOTA‐based ligand (GdL) having one aminobenzyl‐phosphinic acid pendant arm as an MRI probe, and has a statistical composition of (GdL)_6.9‐F_0.1‐β‐CD. Slow rotational dynamics (governed by a very rigid cyclodextrin scaffold) combined with fast water exchange (ensured by the chosen macrocyclic ligand) resulted in a high relaxivity of ～22 s^?1 mM ^?1 per Gd^III or ～150 s^?1 mM ^?1 per molecule of the final conjugate (20 MHz, 25 °C). In vitro labelling of pancreatic islets (PIs) and rat mesenchymal stem cells has been successfully performed. The agent is not cytotoxic and is easily internalized into cells. The labelled cells can be visualized by MRI, as proved by the detection of individual labelled PIs. A fluorescence study performed on mesenchymal stem cells showed that the agent stays in the intracellular space for a long time.     

An Adaptive Interacting Wang–Landau Algorithm for Automatic Density Exploration

While statisticians are well-accustomed to performing exploratory analysis in the modeling stage of an analysis, the notion of conducting preliminary general-purpose exploratory analysis in the Monte Carlo stage (or more generally, the model-fitting stage) of an analysis is an area that we feel deserves much further attention. Toward this aim, this article proposes a general-purpose algorithm for automatic density exploration. The proposed exploration algorithm combines and expands upon components from various adaptive Markov chain Monte Carlo methods, with the Wang–Landau algorithm at its heart. Additionally, the algorithm is run on interacting parallel chains—a feature that both decreases computational cost as well as stabilizes the algorithm, improving its ability to explore the density. Performance of this new parallel adaptive Wang–Landau algorithm is studied in several applications. Through a Bayesian variable selection example, we demonstrate the convergence gains obtained with interacting chains. The ability of the algorithm’s adaptive proposal to induce mode-jumping is illustrated through a Bayesian mixture modeling application. Last, through a two-dimensional Ising model, the authors demonstrate the ability of the algorithm to overcome the high correlations encountered in spatial models. Supplemental materials are available online.     

Dynamic single cell culture array

It is important to quantify the distribution of behavior amongst a population of individual cells to reach a more complete quantitative understanding of cellular processes. Improved high-throughput analysis of single cell behavior requires uniform conditions for individual cells with controllable cell-cell interactions, including diffusible and contact elements. Uniform cell arrays for static culture of adherent cells have previously been constructed using protein micropatterning techniques but lack the ability to control diffusible secretions. Here we present a microfluidic-based dynamic single cell culture array that allows both arrayed culture of individual adherent cells and dynamic control of fluid perfusion with uniform environments for individual cells. In our device no surface modification is required and cell loading is done in less than 30 seconds. The device consists of arrays of physical U-shaped hydrodynamic trapping structures with geometries that are biased to trap only single cells. HeLa cells were shown to adhere at a similar rate in the trapping array as on a control glass substrate. Additionally, rates of cell death and division were comparable to the control experiment. Approximately 100 individual isolated cells were observed growing and adhering in a field of view spanning approximately 1 mm(2) with greater than 85% of cells maintained within the primary trapping site after 24 hours. Also, greater than 90% of cells were adherent and only 5% had undergone apoptosis after 24 hours of perfusion culture within the trapping array. We anticipate uses in single cell analysis of drug toxicity with physiologically relevant perfused dosages as well as investigation of cell signaling pathways and systems biology.     

Open-access microfluidic patch-clamp array with raised lateral cell trapping sites

A novel open-access microfluidic patch-clamp array chip with lateral cell trapping sites raised above the bottom plane of the chip was developed by combining both a microscale soft-lithography and a macroscale polymer fabrication method. This paper demonstrates the capability of using such an open-access fluidic system for patch-clamp measurements. The surface of the open-access patch-clamp sites prepared by the macroscale hole patterning method of soft-state elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are characterized and correlated with the aperture dimensions. Whole cell patch-clamp measurements are carried out with CHO cells expressing Kv2.1 ion channels. Kv2.1 ion channel blocker (TEA) dosage response is characterized and the binding activity is examined. The results demonstrate that the system is capable of performing whole cell measurements and drug profiling in a more efficient manner than the traditional patch-clamp set-up.     

Degree-independent Sobolev extension on locally uniform domains

We consider the problem of constructing extensions , where is the Sobolev space of functions with k derivatives in Lp and Ω⊂Rn is a domain. In the case of Lipschitz Ω, Calderón gave a family of extension operators depending on k, while Stein later produced a single (k-independent) operator. For the more general class of locally-uniform domains, which includes examples with highly non-rectifiable boundaries, a k-dependent family of operators was constructed by Jones. In this work we produce a k-independent operator for all spaces on a locally uniform domain Ω.     

Recrystallization and Precipitate Coarsening in Pb-Free Solder Joints During Thermomechanical Fatigue

The recrystallization of β-Sn profoundly affects deformation and failure of Sn-Ag-Cu solder joints in thermomechanical fatigue (TMF) testing. The numerous grain boundaries of recrystallized β-Sn enable grain boundary sliding, which is absent in as-solidified solder joints. Fatigue cracks initiate at, and propagate along, recrystallized grain boundaries, eventually leading to intergranular fracture. The recrystallization behavior of Sn-Ag-Cu solder joints was examined in three different TMF conditions for five different ball grid array component designs. Based on the experimental observations, a TMF damage accumulation model is proposed: (1) strain-enhanced coarsening of secondary precipitates of Ag₃Sn and Cu₆Sn₅ starts at joint corners, eventually allowing recrystallization of the Sn grain there as well; (2) coarsening and recrystallization continue to develop into the interior of the joints, while fatigue crack growth lags behind; (3) fatigue cracks finally progress through the recrystallized region. Independent of the TMF condition, the recrystallization appeared to be essentially complete after somewhat less than 50% of the characteristic life, while it took another 50% to 75% of the lifetime for a fatigue crack to propagate through the recrystallized region.     

Derivations and Dirichlet forms on fractals

We study derivations and Fredholm modules on metric spaces with a local regular conservative Dirichlet form. In particular, on finitely ramified fractals, we show that there is a non-trivial Fredholm module if and only if the fractal is not a tree (i.e. not simply connected). This result relates Fredholm modules and topology, refines and improves known results on p.c.f. fractals. We also discuss weakly summable Fredholm modules and the Dixmier trace in the cases of some finitely and infinitely ramified fractals (including non-self-similar fractals) if the so-called spectral dimension is less than 2. In the finitely ramified self-similar case we relate the p-summability question with estimates of the Lyapunov exponents for harmonic functions and the behavior of the pressure function.     

Distribution theory on P.C.F. fractals

We construct a theory of distributions in the setting of analysis on post-critically finite self-similar fractals, and on fractafolds and products based on such fractals. The results include basic properties of test functions and distributions, a structure theorem showing that distributions are locally-finite sums of powers of the Laplacian applied to continuous functions, and an analysis of the distributions with point support. Possible future applications to the study of hypoelliptic partial differential operators are suggested.     

Synthesis and Structural Characterization of (Z)-3-[(4-Chlorophenylamino) Methylene] Naphthalene-2(3H)-One: An Enol,Keto or Zwitterionic Tautomer?

Abstract  

The structure of the title compound was determined using X-ray crystallography at both 173 and 293 K. The molecular structure and packing did not change significantly with temperature and a disordered structure was identified comprising a keto and enol tautomeric form. Analysis of the bond lengths in the vicinity of the C=O group suggested the keto form was predominantly in its zwitterionic form structure. ¹H NMR spectroscopy showed the presence of a single compound in solution with two diagnostic doublets demonstrating the compound had an NH group next to a CH group resembling the zwitterionic form of the compound.     

Multipion and strange particle photoproduction off neutrons up to 5.3 GeV

In a study of photoproduction at photon energies up to 5.3 GeV in a deuterium bubble chamber the reactions γn→pπ⁺π^?π^? and γn→pπ⁺π^?π^?π⁰ were analyzed. In these reactions production of the resonances Δ⁺⁺, Δ⁰, ?⁰, ω and A₂^? was observed. Photoproduction of strange particles was investigated and cross sections for the reactions γn→ΛK⁺π^?, Σ^?K⁰π⁺, pK^?K⁰, ΛK⁰π⁺π^? and ΛK⁺π^?π⁰ are presented. Production of Σ^?(1385) and K¹⁰(890) was observed.