Leona Elizabeth Tyler (1906–1993).

Reports the death of L. E. Tyler, who served as the 81st president of the American Psychological Association. Her view was that the purpose of counseling was to encourage natural, life-long developmental processes as distinguished from psychotherapy, which she felt was more appropriate to clinicians' dealings with disturbances of personality. It is noted that Tyler's concern for clarifying the human puzzle of personal change moved, over time, from individual differences to individuality and from a psychometric perspective to a systems–ecological view of real-world choices. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Design, simulation, and performance of a draft tube spout fluid bed coating system for aerogel particles

A draft tube spout fluid bed coating system was designed to coat porous aerogel particles in a size range from 0.1 to 2 mm in diameter. Its primary objective was to insure that just the outer surface of the particles was coated. The inner, pore surface area of the particles needed to remain open to preserve their insulating properties. This paper discusses the design, simulation, and experimental results we obtained on the actual coating of 1-3 mm particles. A conventional, pharmaceutical coating, Surelease®, was used as the coating material and the system successfully coated the particles without penetration of the coating material into the particles. The apparatus can be used to coat friable, low density particles as well as those of high density and is well suited for other coating applications including those in the pharmaceutical industry.     

Fusion-competent vaccines: broad neutralization of primary isolates of HIV

Current recombinant human immunodeficiency virus (HIV) gp120 protein vaccine candidates are unable to elicit antibodies capable of neutralizing infectivity of primary isolates from patients. Here, "fusion-competent" HIV vaccine immunogens were generated that capture the transient envelope-CD4-coreceptor structures that arise during HIV binding and fusion. In a transgenic mouse immunization model, these formaldehyde-fixed whole-cell vaccines elicited antibodies capable of neutralizing infectivity of 23 of 24 primary HIV isolates from diverse geographic locations and genetic clades A to E. Development of these fusion-dependent immunogens may lead to a broadly effective HIV vaccine.     

Increased transversions in a novel mutator colon cancer cell line

We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which increases the spontaneous mutation rate 10-100-fold over background. This mutator results primarily in transversion base substitutions which are found infrequently in repair competent cells. Of the four possible types of transversions, only three were principally recovered. Spontaneous mutations recovered also included transitions and large deletions, but very few frameshifts were recovered. When compared to known mismatch repair defective colon cancer mutators, the distribution of mutations in Vaco411 is significantly different. Consistent with this difference, Vaco411 extracts are proficient in assays of mismatch repair. The Vaco411 mutator appears to be novel, and is not an obvious human homologue of any of the previously characterized bacterial or yeast transversion phenotypes. Several hypotheses by which this mutator may produce transversions are presented.     

Studies on modeling and control of spouted bed reactors—I: Reactor modeling

This paper presents for the first time a theoretical nonisothermal dynamic model for spouted bed catalytic reactors. A pseudo-homogeneous on-dimensional model is developed for an adiabatic spouted-bed with a first order reaction. The effects of various design parameters on the steady-state reactor performance are established.     

Dimension reduction and its application to model-based exploration in continuous spaces

The sample complexity of a reinforcement-learning algorithm is highly coupled to how proficiently it explores, which in turn depends critically on the effective size of its state space. This paper proposes a new exploration mechanism for model-based algorithms in continuous state spaces that automatically discovers the relevant dimensions of the environment. We show that this information can be used to dramatically decrease the sample complexity of the algorithm over conventional exploration techniques. This improvement is achieved by maintaining a low-dimensional representation of the transition function. Empirical evaluations in several environments, including simulation benchmarks and a real robotics domain, suggest that the new method outperforms state-of-the-art algorithms and that the behavior is robust and stable.     

Two-dimensional nonsteady viscous flow simulation on the Navier-Stokes Computer miniNode

The needs of large-scale scientific computation are outpacing the growth in performance of mainframe supercomputers. In particular, problems in fluid mechanics involving complex flow simulations require far more speed and capacity than that provided by current and proposed Class VI supercomputers. To address this concern, the Navier-Stokes Computer (NSC) was developed. The NSC is a parallel-processing machine, comprised of individual Nodes, each comparable in performance to current supercomputers. The global architecture is that of a hypercube, and a 128-Node NSC has been designed. New architectural features, such as a reconfigurable many-function ALU pipeline and a multifunction memory-ALU switch, have provided the capability to efficiently implement a wide range of algorithms. Efficient algorithms typically involve numerically intensive tasks, which often include conditional operations. These operations may be efficiently implemented on the NSC without, in general, sacrificing vector-processing speed. To illustrate the architecture, programming, and several of the capabilities of the NSC, the simulation of two-dimensional, nonsteady viscous flows on a prototype Node, called the miniNode, is presented.     

Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha

A human MSH2-human MSH3 (hMSH2.hMSH3) complex of approximately 1:1 stoichiometry (human MutSbeta (hMutSbeta)) has been demonstrated in several human tumor cell lines and purified to near homogeneity. In vitro, hMutSbeta supports the efficient repair of insertion/deletion (I/D) heterologies of 2-8 nucleotides, is weakly active on a single-nucleotide I/D mispair, and is not detectably active on the eight base-base mismatches. Human MutSalpha (hMutSalpha), a heterodimer of hMSH2 and hMSH6, efficiently supports the repair of single-nucleotide I/D mismatches, base-base mispairs, and all substrates tested that were repaired by hMutSbeta. Thus, the repair specificities of hMutSalpha and hMutSbeta are redundant with respect to the repair of I/D heterologies of 2-8 nucleotides. The hMutSalpha level in repair-proficient HeLa cells (1.5 microg/mg nuclear extract) is approximately 10 times that of hMutSbeta. In HCT-15 colorectal tumor cells, which do not contain hMSH6 and consequently lack hMutSalpha, the hMutSbeta level is elevated severalfold relative to that in HeLa cells and is responsible for the repair of I/D mismatches that has been observed in this cell line. LoVo tumor cells, which are genetically deficient in hMSH2, lack both hMutSalpha and hMutSbeta, and hMSH3 and hMSH6 levels are less than 4% of those found in repair-proficient cells. Coupled with previous findings (J. T. Drummond, J. Genschel, E. Wolf, and P. Modrich (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 10144-10149), these results suggest that hMSH2 partitions between available pools of hMSH3 and hMSH6 and indicate that hMSH2 positively modulates hMSH6 and hMSH3 levels, perhaps by stabilization of the polypeptides upon heterodimer formation.     

An enhancer that directs lineage-specific expression of CD8 in positively selected thymocytes and mature T cells

Positive selection of CD4+CD8+ T cells to the CD4+CD8- helper and CD4- CD8+ cytotoxic lineages is a multistep process that involves complex regulation of coreceptor gene expression. By analyzing expression of a reporter gene in transgenic mice, we have identified a DNA segment, located between the murine CD8beta and CD8alpha genes, that has enhancer activity restricted to CD8 lineage cells. Remarkably, this enhancer functions in thymocytes undergoing positive selection to the CD4-CD8+ phenotype but not in immature double-positive thymocytes. The enhancer also functions in gut intraepithelial lymphocytes that express CD8alpha but not CD8beta, suggesting that it is specific for CD8alpha expression. The tight correlation between activation of this enhancer and the final step in positive selection has important implications for understanding the mechanism of lineage commitment in thymocytes.