Lead differentially modifies cytokine production in vitro and in vivo

An imbalance between helper T cell type 1 (Th1) and helper T cell type 2 (Th2) activation can result in immunodysregulations leading to impaired cell-mediated immunity with an increased incidence of infectious disease or cancer and/or aberrant humoral immunity that may culminate with an autoimmune disease. Mercury, a heavy-metal toxicant, is known to induce renal autoimmunity characterized by a predominant Th2 response. Lead, another metal toxicant, causes enhanced B cell activities and impairs host resistance to several bacterial and viral infections. In addition, Pb was reported to enhance Th2 proliferation and inhibit Th1 proliferation. The differential effects of Pb on Th subset activation have been further investigated. In vitro IL-4 production by a Th2 clone was significantly increased by the addition of PbCl2, whereas IFN gamma production by a Th1 clone was decreased by the addition of PbCl2. When BALB/c mice were subcutaneously exposed to PbCl2, ex vivo Il-4 production by anti-CD3-stimulated splenic T cells was enhanced, but IFN gamma production was inhibited. Additionally, the plasma IL-4 and IgE levels of Pb-exposed mice were increased, and the plasma IFN gamma levels were significantly lowered in the absence of any additional exogenous antigen. In vitro, ex vivo, and in vivo treatment with HgCl2 produced similar findings. This study is the first report of the preferential activation of a Th2 response by Pb in vivo and suggests that PB, like Hg, may induce autoimmune responses by upsetting the balance between Th1- and Th2-like cells, which could enhance production of antibodies to self antigens.     

A base-pairing interaction between U2 and U6 small nuclear RNAs occurs in > 150S complexes in HeLa cell extracts: implications for the spliceosome assembly pathway

In mammalian cells, base pairing between the U2 and U6 small nuclear RNAs is required during pre-RNA splicing. We show by psoralen crosslinking of HeLa nuclear extract that U2.U6 base pairing occurs within abundant ribonucleoprotein complexes that sediment at > 150 S in glycerol gradients. All of the spliceosomal RNAs (U1, U2, U4, U5, and U6) cosediment with these large complexes, suggesting that they may be related to small nuclear RNA-containing structures called speckles/coiled bodies or snurposomes, which have been visualized in mammalian or amphibian nuclei, respectively. In contrast to nuclear extract, S100 extract, which is splicing-defective and lacks the > 150S complexes, does not contain base-paired U2.U6. However, U2.U6 base pairs form in S100 extract that has been made splicing-competent by supplementation with Ser/Arg-rich (SR) proteins, ATP, and an adenovirus splicing substrate. During splicing in supplemented S100 extract, U2.U6 base pairing precedes the appearance of splicing intermediates and occurs initially in an approximately 60S spliceosome complex but also in progressively larger (100-300 S) complexes. Possible functional relationships between the 60S spliceosome and the > 150S complexes are discussed.     

New and used temporal models: An issue of time

TheSpecial Issue on Applications of Temporal Models raises many issues of time: What are the important properties of time? How can time be best represented? How can one reason about time-dependent properties? What are the important directions of temporal research? This introductory piece very briefly surveys the current wide variety of temporal models, temporal reasoning methods, and applications to time-varying phenomena. Promising areas of investigation such as the verification of concurrent systems, knowledge-base representation methods, and dealing with theFrame Problem pass in fleeting review. Brief introductions to each of the works in the volume close the section.     

Extending the Kernighan/Lin Heuristic for Hardware and Software Functional Partitioning

The Kernighan/Lin graph partitioning heuristic, also known as min-cut or group migration, has been extended over several decades very successfully for circuit partitioning. Those extensions customized the heuristic and its associated data structure to rapidly compute the minimum-cut metric central to circuit partitioning; as such, those extensions are not directly applicable to other problems. In this paper, we extend the heuristic for functional partitioning, which in turn can solve the much investigated codesign problem of partitioning a system's coarse-grained functions among hardware and software components. The key extension customizes the heuristic and data structure to rapidly compute execution-time and communication metrics, crucial to hardware and software partitioning, and leads to near-linear time-complexity and excellent resulting quality. Another extension uses a new criteria for terminating the heuristic, eliminating time-consuming and unnecessary fine-tuning of a partition. Our experiments demonstrate extremely fast execution times (just a few seconds) with results matched only by the slower simulated annealing heuristic, meaning that the extended Kernighan/Lin heuristic will likely prove hard to beat for hardware and software functional partitioning.     

Estimates of the dollar value of employee output in utility analyses: An empirical test of two theories.

Examined distributions of estimates of the dollar value of performance in studies employing the method of F. L. Schmidt et al (1979) for estimating the standard deviation of job performance (SDy) and found evidence that (1) the mean 50th percentile estimate is biased downward, (2) estimates of SDy appear to be a constant percentage of the 50th percentile estimate, and (3) estimates of SDy as a percentage of the 50th percentile value (SDp) are quite similar to empirical SDp values based on actual employee output. These findings suggest that the downward bias in the mean estimate of the 50th percentile causes the mean estimates of SDy to be similarly biased downward, but does not bias the estimates of SDp. Finally, an objective method for estimating the value of average employee output is described. The product of this value and the mean supervisory estimate of SDp yields an unbiased estimate of SDy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A set of electrophoretic molecular markers for strain typing and population genetic studies of Histoplasma capsulatum

A set of eleven biallelic and three multiallelic molecular markers have been developed to analyze populations of Histoplasma capsulatum. All markers are amplified by polymerase chain reaction (PCR) and can be readily scored using minimal amounts of template DNA. The 11 biallelic loci have polymorphic restriction endonuclease sites or small insertions or deletions which may be assessed by agarose gel electrophoresis. These markers are inherited in an unambiguous manner and are ideal for assessing structure and gene flow within US populations of H. capsulatum, but are monomorphic in non-US populations. Both length and sequence variation are present in the multiallelic loci, which can be scored by direct sequencing, polyacrylamide gel electrophoresis, or single-strand conformation polymorphism (SSCP): As they are hypervariable, the multiallelic loci can be used to type isolates and to assess the level of genetic variation within populations. Preliminary results indicate that the three multiallelic markers presented are sufficient to distinguish isolates at the individual level and are polymorphic in both US and non-US populations. This collection of molecular markers will be a useful tool in population and epidemiology studies of H. capsulatum.