Sparse-grid-based adaptive model predictive control of HL60 cellular differentiation

Quantitative methods such as model-based predictive control are known to facilitate the design of strategies to manipulate biological systems. This study develops a sparse-grid-based adaptive model predictive control (MPC) strategy to direct HL60 cellular differentiation. Sparse-grid sampling and interpolation support a computationally efficient adaptive MPC scheme in which multiple data-consistent regions of the model parameter space are identified and used to calculate a control compromise. The algorithm is evaluated in silico with structural model mismatch. Simulations demonstrate how the multiscenario control strategy more effectively manages the mismatch compared to a single scenario approach. Furthermore, the controller is evaluated in vitro to differentiate HL60 cells in both normal and perturbed environments. The controller-derived input sequence successfully achieves and sustains the specified target level of granulocytes when implemented in the laboratory. The results and analysis given here imply that adoption of this experiment planning technique to direct cell differentiation within more complex tissue engineered constructs will require the use of a reasonably accurate mathematical model and an extension of this algorithm to multiobjective controller design.     

Generation of protein lattices by fusing proteins with matching rotational symmetry

The self-assembly of supramolecular structures that are ordered on the nanometre scale is a key objective in nanotechnology. DNA and peptide nanotechnologies have produced various two- and three-dimensional structures, but protein molecules have been underexploited in this area of research. Here we show that the genetic fusion of subunits from protein assemblies that have matching rotational symmetry generates species that can self-assemble into well-ordered, pre-determined one- and two-dimensional arrays that are stabilized by extensive intermolecular interactions. This new class of supramolecular structure provides a way to manufacture biomaterials with diverse structural and functional properties.     

Response Surface Methodology for Reduction of Pinking in Cooked Turkey Breast Mince by Various Dairy Protein Combinations

Nonfat dry milk (NFDM), sodium caseinate (SC), whey protein concentrate (WPC), and combinations of each were evaluated for abilities to reduce pink color development in cooked, ground, uncured turkey breast. Protein treatments were also evaluated in the presence of pink-color-generating ligands (nicotinamide, 1%, sodium nitrite, 10 ppm, and sodium nitrate, 50 ppm) with and without ethylenedinitrilo-tetraacetic acid disodium salt (200 ppm). NFDM and WPC at levels as low as 1.5% were effective in reducing CIE a* values (P < 0.05) regardless of ligand treatment; SC was not. EDTA reduced pink color within all protein and ligand treatments. Poultry producers can reduce pink color development in further-processed products by selective addition of dairy proteins.     

High selectivity of the i(f) channel to Na+ and K+ in rabbit isolated sinoatrial node cells

The ionic selectivity of the hyperpolarization-activated inward current (i(f)) channel to monovalent cations was investigated in single isolated sinoatrial node cells of the rabbit using the whole-cell patch-clamp technique. With a 140 mM K+ pipette, replacement of 90% external Na+ by Li+ caused a -24.5 mV shift of the fully activated current/voltage I/V curve without a significant decrease of the slope conductance. With a 140 mM Cs+ pipette, the i(f) current decreased almost proportionally to the decrease in external [Na+]o as Li+ was substituted. These responses are practically the same as those observed with N-methyl glucamine (NMG+) substitution, suggesting that the relative permeability of Li+ compared with Na+ for the i(f) channel is as low as that of NMG+. When Cs+ or Rb+ was substituted for internal K+, the fully activated I/V relationship for i(f) showed strong inward rectification with a positive reversal potential, indicating low permeability of the i(f) channel for Cs+ and Rb+. These results show that the i(f) channel is highly selective for Na+ and K+ and will not pass the similar ions Li+ and Rb+. Such a high degree of selectivity is unique and may imply that the structure of the i(f) channel differs greatly from that of other Na+ and K+ conducting channels.     

Sensory evaluation of bitterness and astringency of 3R(−)-epicatechin and 3S(+)-catechin

Bitterness and astringency of the monomeric flavan-3-o!s ( + )-catechin and (?)-epicatechin were rated using time-intensity (T-I) methodology. Three concentration levels (0.5. 0.9 and 1.2 g liter^?1) oi each compound were assessed, and the parameters time to maximum intensity (TMAX), intensity at the maximum (IMAX) and total duration (TTOT) were extracted from the T-I curves. No differences in TMAX for either bitterness or astringency were found between these chiral isomers or as a function of concentration within a compound. Epicatechin had a significantly higher bitter IMAX than catechin at all three concentration levels, and had a significantly longer TTOT at the two higher concentrations. Epicatechin was more astringent than catechin. but this was only significant at one concentration. Astringency TTOT was longer for epicatechin, although this was nonsignificant at the lowest concentration. The three concentrations of catechin were significantly different for both bitterness and astringency IMAX and TTOT. Epicatechin showed evidence for the astringency response plateauing above the 0.9 g litre^?1 level. n-Propylthiouracil status had no effect on perception of either bitterness or astringency.     

Pressurization and centralization enhance the quality and reproducibility of cement mantles

Cementing technique has a profound influence on the incidence of aseptic loosening of total hip replacements. Two specific measures that seem to have the greatest impact on the longevity of cemented femoral stems are pressurization of cement and control of mantle thickness, typically through the use of modular centralizing devices attached to the tip of the prosthesis. Two laboratory studies are presented that examine the success of these measures in clinical practice. In the first study, the performance of five designs of intramedullary plugs in resisting migration during pressurization of cement was evaluated in human anatomic specimen femurs. Profound differences were observed between the performance of the different plug designs. In canals larger than 12 to 14 mm, most commercial devices failed to resist pressures greater than 30 to 40 pounds per square inch. Overall, it was estimated that between 6% to 76% of these devices would fail to resist cement pressures of 50 pounds per square inch in clinical practice. The second study examined the role of distal centralizers in the accumulation of air bubbles around the distal tip of the prosthesis during insertion of the stem into the femur. Acrylic replicas of a femoral stem were implanted in cavities simulating the femoral canal. Colored dyes, present within the cement, revealed the complex patterns of cement flow. It was shown that cement, dragged from the top of the femur, forms a thin layer that covers the entire surface of the prosthesis and the distal centralizer. Significant voids were present behind the trailing edges of the distal centralizer in 42% of the cases examined. These studies show that improvements in intramedullary plugs and stem centralizers are needed to increase the reproducibility of cement technique in total hip replacement.     

LWR development in the USA

The U.S. Nuclear Power Industry is developing improved reactor systems to be prepared for the expected need of new base load electric generating capacity in the 1990s. The approach being taken is to build upon the large base of existing light water reactor technology, making evolutionary improvements, and finding innovative ways to simplify, shorten construction time, and reduce cost. The U.S. reactor manufacturers, working in collaboration with Japanese utilities, are developing 1300 MWe improved designs. This paper reviews the EPRI ALWR Program which is coordinated with these efforts by the reactor manufacturers. Emphasis is given to that portion of the EPRI Program dealing with conceptual design of smaller rated Advanced Simplified LWRs using passive system design to accomplish major simplification.