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The study of signal transduction processes using antisense oligonucleotides is often complicated by low intracellular stability of the antisense reagents or by nonspecific effects that cause toxicity. Here, we introduce a new class of antisense molecules, so-called GeneBlocs, which are characterized by improved stability, high target RNA specificity, and low toxicity. GeneBlocs allow for efficient downregulation of mRNA expression at nanomolar concentrations, and they do not interfere with cell proliferation. We demonstrate these beneficial properties using a positive readout system. GeneBloc-mediated inhibition of tumor suppressor PTEN (phosphatase and tension homologue detected on chromosome 10) expression leads to hyperactivation of the phosphatidylinositol (PI) 3-kinase pathway, thereby mimicking the loss of PTEN function and its early consequences observed in mammalian cancer cells. Specifically, cells treated with PTEN GeneBlocs show functional activation of Akt, a downstream effector of PI 3-kinase signaling, and exhibit enhanced proliferation when seeded on a basement membrane matrix. In addition, GeneBlocs targeting the catalytic subunit of PI 3-kinase, p110, specifically inhibit signal transduction of endogenous or recombinant PI 3-kinase. This demonstrates that GeneBlocs are powerful tools to analyze and to modulate signal transduction processes and, therefore, represent alternative reagents for the validation of gene function.

The International Space Station (ISS) is an engineering project unlike any other. The vehicle is inhabited and operational as it is constructed. The habitability resources available to the crew are the sleep quarters, the galley, the waste and hygiene compartment, and exercise equipment. These items are mainly in the Russian Service Module and their placement is awkward for the crew to use and work around. ISS assembly will continue with the truss build and the addition of the International Partner Laboratories. Prior to the addition of the International Partner Laboratories. Node 2 will be added. The Node 2 module will provide additional stowage volume and room for more crew sleep quarters. The purpose of the ISS is to perform research and a major area of emphasis is on the effects of long duration space flight on humans, as result of this research the habitability requirements for the International Space Station crews will be determined.

Deletion mutant analysis of the mercury-resistant determinant (mer operon) from the Staphylococcus aureus plasmid pI258 was used to verify the location of the merA and merB genes and to show the existence of mercuric ion transport gene(s). ORF5 was confirmed to be a transport gene and has an amino acid product sequence homologous to the merT gene products from several gram-negative bacteria and a Bacillus species. Deletion analysis established that inactivation of merA on a broad-spectrum mer resistance determinant resulted in a mercury-hypersensitive phenotype. Gene dosage had no apparent effect on the level of resistance conferred by the intact mer operon or on the expression of an inducible phenotype, except that when the intact pI258 mer operon was on a high copy number plasmid, uninduced cells possessed a volatilization rate that was at most only 3.5-fold less than that observed for induced cells. There was no need for mercury ion transport proteins for full resistance when the mer operon was expressed in a high copy number plasmid. Key words: mercury resistance, Staphylococcus aureus plasmid.

During failure analysis on high voltage I3T50 products, it was found that irregular Nsinker regions were present in the top region of the wafer. This Nsinker distortion, also called POCl3 deformation, was shown during failure analysis to be linked to certain binnings within the yield loss. A decoration technique has been developed to detect POCl3 deformations inline with KLA, and it is shown that drying marks in trenches in the Deep Trench Isolation (DTI) module are the root cause of POCl3 deformation. An improved drying technique has been put in place, thus preventing the defects observed.