Human neural stem cell growth and differentiation in a gradient-generating microfluidic device

This paper describes a gradient-generating microfluidic platform for optimizing proliferation and differentiation of neural stem cells (NSCs) in culture. Microfluidic technology has great potential to improve stem cell (SC) cultures, whose promise in cell-based therapies is limited by the inability to precisely control their behavior in culture. Compared to traditional culture tools, microfluidic platforms should provide much greater control over cell microenvironment and rapid optimization of media composition using relatively small numbers of cells. Our platform exposes cells to a concentration gradient of growth factors under continuous flow, thus minimizing autocrine and paracrine signaling. Human NSCs (hNSCs) from the developing cerebral cortex were cultured for more than 1 week in the microfluidic device while constantly exposed to a continuous gradient of a growth factor (GF) mixture containing epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2) and platelet-derived growth factor (PDGF). Proliferation and differentiation of NSCs into astrocytes were monitored by time-lapse microscopy and immunocytochemistry. The NSCs remained healthy throughout the entire culture period, and importantly, proliferated and differentiated in a graded and proportional fashion that varied directly with GF concentration. These concentration-dependent cellular responses were quantitatively similar to those measured in control chambers built into the device and in parallel cultures using traditional 6-well plates. This gradient-generating microfluidic platform should be useful for a wide range of basic and applied studies on cultured cells, including SCs.     

Nonequilibrium synthesis and assembly of hybrid inorganic-protein nanostructures using an engineered DNA binding protein

We show that a protein with no intrinsic inorganic synthesis activity can be endowed with the ability to control the formation of inorganic nanostructures under thermodynamically unfavorable (nonequilibrium) conditions, reproducing a key feature of biological hard-tissue growth and assembly. The nonequilibrium synthesis of Cu(2)O nanoparticles is accomplished using an engineered derivative of the DNA-binding protein TraI in a room-temperature precursor electrolyte. The functional TraI derivative (TraIi1753::CN225) is engineered to possess a cysteine-constrained 12-residue Cu(2)O binding sequence, designated CN225, that is inserted into a permissive site in TraI. When TraIi1753::CN225 is included in the precursor electrolyte, stable Cu(2)O nanoparticles form, even though the concentrations of [Cu(+)] and [OH(-)] are at 5% of the solubility product (K(sp,Cu2O)). Negative control experiments verify that Cu(2)O formation is controlled by inclusion of the CN225 binding sequence. Transmission electron microscopy and electron diffraction reveal a core-shell structure for the nonequilibrium nanoparticles: a 2 nm Cu(2)O core is surrounded by an adsorbed protein shell. Quantitative protein adsorption studies show that the unexpected stability of Cu(2)O is imparted by the nanomolar surface binding affinity of TraIi1753::CN225 for Cu(2)O (K(d) = 1.2 x 10(-)(8) M), which provides favorable interfacial energetics (-45 kJ/mol) for the core-shell configuration. The protein shell retains the DNA-binding traits of TraI, as evidenced by the spontaneous organization of nanoparticles onto circular double-stranded DNA.     

Linear covering codes and error-correcting codes for limited-magnitude errors

The concepts of a linear covering code and a covering set for the limited-magnitude-error channel are introduced. A number of covering-set constructions, as well as some bounds, are given. In particular, optimal constructions are given for some cases involving small-magnitude errors. A problem of Stein is partially solved for these cases. Optimal packing sets and the corresponding error-correcting codes are also considered for some small-magnitude errors.     

Nondeterministic approach to tree-based jet substructure

Jet substructure is typically studied using clustering algorithms, such as k(T), which arrange the jets' constituents into trees. Instead of considering a single tree per jet, we propose that multiple trees should be considered, weighted by an appropriate metric. Then each jet in each event produces a distribution for an observable, rather than a single value. Advantages of this approach include (1) observables have significantly increased statistical stability, and (2) new observables, such as the variance of the distribution, provide new handles for signal and background discrimination. For example, we find that employing a set of trees substantially reduces the observed fluctuations in the pruned mass distribution, enhancing the likelihood of new particle discovery for a given integrated luminosity. Furthermore, the resulting pruned mass distributions for (background) QCD jets are found to be substantially wider than that for (signal) jets with intrinsic mass scales, e.g., boosted W jets. A cut on this width yields a substantial enhancement in significance relative to a cut on the standard pruned jet mass alone. In particular the luminosity needed for a given significance requirement decreases by a factor of 2 relative to standard pruning.     

Langmuir-Blodgett film structure

Langmuir-Blodgett (LB) films occupy a unique niche at the crossroads of materials science, complex fluids, and biophysics. They have many similarities to inorganic epitaxial films due to the layer by layer deposition process; however, the amphiphilic nature of the constituent molecules provides the connection to lyotropic liquid crystals and membranes. A great deal is known about LB film structure and thermodynamic behavior; both from classical studies as well as from recent experiments using sophisticated characterization techniques such as synchrotron X-ray scattering and scanning probe microscopy. This article summarizes the current understanding of these systems from a physical/structural point of view. Included are discussions of the deposition process, the layered nature of LB films, intralayer molecular packing, defects, stability, and phase transitions.     

Design and optimal tuning of nonlinear PI compensators

In this paper, linear time-invariant single-input single-output (SISO) systems that are stabilizable by linear proportional and integral (PI) compensators are considered. For such systems, a five-parameter nonlinear PI compensator is proposed. The parameters of the proposed compensator are tuned by solving an optimization problem. The optimization problem always has a solution.Additionally, a general nonlinear PI compensator is proposed and is approximated by easy-to-compute compensators, for instance, a six-parameter nonlinear PI compensator. The parameters of the approximate compensators are tuned to satisfy an optimality condition. The superiority of the proposed nonlinear PI compensators over linear PI compensators is discussed and is demonstrated for two feedback systems.