Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype

The biological phenotype of primary human immunodeficiency virus type 1 (HIV-1) isolates varies according to the severity of the HIV infection. Here we show that the two previously described groups of rapid/high, syncytium-inducing (SI) and slow/low, non-syncytium-inducing (NSI) isolates are distinguished by their ability to utilize different chemokine receptors for entry into target cells. Recent studies have identified the C-X-C chemokine receptor CXCR4 (also named fusin or Lestr) and the C-C chemokine receptor CCR5 as the principal entry cofactors for T-cell-line-tropic and non-T-cell-line-tropic HIV-1, respectively. Using U87.CD4 glioma cell lines, stably expressing the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4, we have tested chemokine receptor specificity for a panel of genetically diverse envelope glycoprotein genes cloned from primary HIV-1 isolates and have found that receptor usage was closely associated with the biological phenotype of the virus isolate but not the genetic subtype. We have also analyzed a panel of 36 well-characterized primary HIV-1 isolates for syncytium induction and replication in the same series of cell lines. Infection by slow/low viruses was restricted to cells expressing CCR5, whereas rapid/high viruses could use a variety of chemokine receptors. In addition to the regular use of CXCR4, many rapid/high viruses used CCR5 and some also used CCR3 and CCR2b. Progressive HIV-1 infection is characterized by the emergence of viruses resistant to inhibition by beta-chemokines, which corresponded to changes in coreceptor usage. The broadening of the host range may even enable the use of uncharacterized coreceptors, in that two isolates from immunodeficient patients infected the parental U87.CD4 cell line lacking any engineered coreceptor. Two primary isolates with multiple coreceptor usage were shown to consist of mixed populations, one with a narrow host range using CCR5 only and the other with a broad host range using CCR3, CCR5, or CXCR4, similar to the original population. The results show that all 36 primary HIV-1 isolates induce syncytia, provided that target cells carry the particular coreceptor required by the virus.     

Knows what it knows: a framework for self-aware learning

We introduce a learning framework that combines elements of the well-known PAC and mistake-bound models. The KWIK (knows what it knows) framework was designed particularly for its utility in learning settings where active exploration can impact the training examples the learner is exposed to, as is true in reinforcement-learning and active-learning problems. We catalog several KWIK-learnable classes as well as open problems, and demonstrate their applications in experience-efficient reinforcement learning.     

Stochastic Boolean Satisfiability

Satisfiability problems and probabilistic models are core topics of artificial intelligence and computer science. This paper looks at the rich intersection between these two areas, opening the door for the use of satisfiability approaches in probabilistic domains. The paper examines a generic stochastic satisfiability problem, SSAT, which can function for probabilistic domains as SAT does for deterministic domains. It shows the connection between SSAT and well-studied problems in belief network inference and planning under uncertainty, and defines algorithms, both systematic and stochastic, for solving SSAT instances. These algorithms are validated on random SSAT formulae generated under the fixed-clause model. In spite of the large complexity gap between SSAT (PSPACE) and SAT (NP), the paper suggests that much of what we have learned about SAT transfers to the probabilistic domain.     

A new spouting regime in beds of coarse particles deeper than the maximum spoutable height

A new spouting regime for coarse particles in beds deeper than the maximum spoutable height has been identified and its location on a phase diagram is presented for an air spouted bed of 5 mm glass spheres. The periodic formation and breakup of single bubbles originating at the top of the spout at lower gas velocities than required to observe the new regime has been studied using high speed photographs. An analogy is drawn between these observations and the breakup of bubbles in a turbulently fluidized bed.     

Reducing reinforcement learning to KWIK online regression

One of the key problems in reinforcement learning (RL) is balancing exploration and exploitation. Another is learning and acting in large Markov decision processes (MDPs) where compact function approximation has to be used. This paper introduces REKWIRE, a provably efficient, model-free algorithm for finite-horizon RL problems with value function approximation (VFA) that addresses the exploration-exploitation tradeoff in a principled way. The crucial element of this algorithm is a reduction of RL to online regression in the recently proposed KWIK learning model. We show that, if the KWIK online regression problem can be solved efficiently, then the sample complexity of exploration of REKWIRE is polynomial. Therefore, the reduction suggests a new and sound direction to tackle general RL problems. The efficiency of our algorithm is verified on a set of proof-of-concept experiments where popular, ad hoc exploration approaches fail.     

Jet penetration and pressure drops in water spouted beds of fine particles

New expressions for the maximum spoutable height and spout pressure drop ratio are developed for fine particles spouted in water. The maximum spoutable height in both water and air systems is found to be dependent upon two dimensionless parameters, β and A_Lim. For fine particles spouted with water, the dimensionless pressure drop ratio depends only upon the voidage, ? at the bottom of the spout.     

Dominance behavior of paired primates in two settings.

3 species of monkeys (1 male pigtail, 3 male and 2 female militaries, and 1 male and 2 female monas) were tested by paired comparisons for dominance. The 2 settings were a Wisconsin General Test Apparatus and a room-size Skinner-type lever apparatus. The major indices of dominance were aggression, retaliation, and the amount of food consumed. Intrasession dominance relations were very stable and the correlations between settings ranged from moderate (rho = .60) to high (rho = .90). Aggression was a function of proximity in the dominance hierarchy, the absolute level in the hierarchy, species, and weight. The findings were discussed in relation to the nature of the task and ecological considerations; finally, monkey behavior was contrasted with rat behavior in similar situations in terms of ability to comprehend problems and natural modes of competitive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychology: The socially indifferent science.

Psychology "is a science without social content… . I believe that psychology has been and ought to be mainly interested in the properties and processes of individual organisms… . Psychology… has been so far the science which deals with the abstract, universal, culturally contentless features of behavior which in almost all cases—and surely all the most interesting cases—are socially tagged, but which are analyzed as properties of individual organisms… . I am arguing that the formulations which psychologists have made and ought to continue making do not and need not contain explicit social or cultural terms to satisfy the relevance of psychology for understanding social behavior." From Psyc Abstracts 36:02:2AD32L. (PsycINFO Database Record (c) 2010 APA, all rights reserved)