Expression of a D2 dopamine receptor antisense RNA in brain inhibits D2-mediated behaviors

We reported that 3'-azidothymidine-3'-deoxythymidine (AZT) plus 5-fluorouracil or methotrexate produces additive cytotoxicity in HCT-8 cells: a reflection of increased AZT metabolism when de novo thymidylate (dTMP) synthesis was inhibited. We now report that AZT plus human recombinant interferon alpha-2a (rIFN-alpha 2a) produces synergistic growth inhibition in these cells. Evaluation of the effect of rIFN-alpha 2a on dTMP metabolism revealed that exposure to rIFN-alpha 2a (+/-AZT) did not affect dTMP synthase activity significantly but increased thymidine (dThd) kinase activity significantly. Consequently, AZT nucleotide production and incorporation into DNA were increased by coexposure to rIFN-alpha 2a. This alone, however, cannot explain the observed synergism. Therefore, the effect of these agents on DNA excision/repair processes was assessed. Isotope clearance studies demonstrated that rIFN-alpha 2a did not alter the rate of [3H]AZT excision from DNA. In contrast, filter-elution studies revealed that rIFN-alpha 2a (+/-AZT) produced more DNA damage and delayed repair compared with the effects produced by AZT alone. Since DNA polymerases alpha and beta are directly involved in gap-filling repair synthesis, experiments next assessed the effect of rIFN-alpha 2a and/or 3'- azido-3'-deoxythymidine-5'-triphosphate (AZTTP) on their activities. Polymerase alpha was inhibited slightly by AZTTP but not by rIFN-alpha 2a. Polymerase beta activity, however, was inhibited dramatically by rIFN-alpha 2a + AZTTP. Finally, western analysis revealed that a 24-hr exposure to 5000 IU/mL rIFN-alpha 2a (+/-20 microM AZT) significantly reduced wild-type p53 expression compared with AZT-exposed cells. We conclude that rIFN-alpha 2a enhances AZT-induced tumor cell growth inhibition by (i) increasing AZT metabolism, and (ii) inhibiting DNA repair and p53-mediated cell cycle control processes.     

Some experiments with a simple tabu search algorithm for the manufacturer's pallet loading problem

The manufacturer's pallet loading problem consists in arranging, orthogonally and without overlapping, the maximum number of boxes with dimensions (l,w) or (w,l) onto a rectangular pallet with dimensions (L,W). This problem has been successfully handled by block heuristics, which generate loading patterns composed by one or more blocks where the boxes have the same orientation. A common feature of such methods is that the solutions provided are limited to the so-called first order non-guillotine patterns. In this paper we propose an approach based on the incorporation of simple tabu search (without longer-term memory structures) in block heuristics. Starting from an initial loading pattern, the algorithm performs moves that increase the size of selected blocks in the current pattern; as a result, other blocks are decreased, eliminated or created. Computational results indicate that the approach is capable of generating superior order optimal patterns for difficult instances reported in the literature.     

Chlorambucil synergizes with purine analogs in inducing in vitro cytotoxicity in B-cell chronic lymphocytic leukemia

Combinations of different drug concentrations of CLB + FAMP and CLB + 2-CDA were synergistic in, respectively, 42.9% and 34.8%. At leukemic cell survival < or = 50%, 16.4% and 23.4% of all combinations were synergistic in the 2-CDA and FAMP groups, respectively. A significantly higher mean value of antagonistic interactions was observed in the 2-CDA group (p = 0.037).     

Modeling intramedia and intermedia relationships in multimedia network analysis through multiple timescale statistics

In this paper, a hierarchical paradigm modeling both the intramedia and intermedia time relationships of multimedia sources is derived. Each multimedia source is considered as being made up of a master monomedia source, which is independent, and slave monomedia sources, which are dependent on the master. The paradigm takes different timescale statistics into account and is used to characterize intermedia relationships in terms of the second-order statistics of the multimedia source. Finally, the impact of intermedia relationships on the performance of each monomedia source making up a multimedia source is analyzed when a number of multimedia sources are multiplexed together. The error introduced in both loss and jitter performance analysis when intermedia relationships are not modeled is evaluated through a case study. Numerical results show that this error may be dramatically significant in many common scenarios.     

TGF-beta knockout and dominant-negative receptor transgenic mice

Use of homologous recombination and transgenic technologies have provided mouse models to study the physiological roles of the three mammalian TGF-beta isoforms, and their regulation in the context of the intact animal. Mice harboring null mutations for TGF-beta isoforms demonstrate that each exerts discrete nonoverlapping functions during development. TGF-beta1 null mice reveal a crucial role for this cytokine in modulation of the immune system, with evidence for altered development, activation and function of various immune cell populations. New approaches to tissue- and cell-restricted disruption of TGF-beta signaling pathways in transgenic mice carrying dominant-negative mutant TGF-beta receptors will be discussed.     

An analytical framework for the design of intelligent algorithms for adaptive-rate MPEG video encoding in next-generation time-varying wireless networks

Adaptive rate video encoding is required to maximize efficiency when wireless links are involved in the communication. In fact, wireless channels are characterized by high, time-varying bit error rates. To cope efficiently with this problem adaptive forward error correction schemes have been proposed. These schemes introduce an amount of redundancy dependent on the channel conditions. Accordingly, the bandwidth available at the application layer changes: it increases when channel conditions improve, and decreases when channel conditions worsen. Obviously, the encoding parameters must be tuned to adapt the video source transmission rate to the available bandwidth. This adaptation is achieved by means of appropriate feedback laws, which are relationships between the encoding parameters to be used and other variables representing the state of the system. An analytical framework is introduced which can be used for the design of the feedback laws. To this purpose both the channel and the video source are modeled by means of Markov models. The resulting model of the whole system is denoted as SBBP/SBBP/1/K. Analysis is derived which allows to evaluate the most significant performance measures and, therefore, to design optimal feedback laws.     

Which cutoff level should be used in screening for glucose intolerance in pregnancy? Definition of Screening Methods for Gestational Diabetes Study Group of the Lombardy Section of the Italian Society of Diabetology

A Candida albicans expression library was constructed from RNA isolated from regenerating protoplasts. A 1.4-kb cDNA clone was used to isolate a genomic fragment. Sequence analysis revealed an open reading frame of 593 amino acids with an overall identity of 63.6% with the phenylalanyl-tRNA synthetase beta subunit (FRS1) of Saccharomyces cerevisiae. We named it CaFRS1. It is located in a single copy in chromosome R, SfiI fragment M. Its expression showed a decrease during the cell wall regeneration process in protoplasts of both yeast and mycelial cells of C. albicans, suggesting its requirement thereof in initial steps of the cell wall synthesis.     

Recent advances in solder bond technology for microelectronic packaging

The recent advances in solder bond technology which have occured in the metallurgical, chemical and mechanical fields for both macroconnections and microconnections have caused a rapid acceleration in the use of solder in microelectronics packaging.Relatively soluble metallurgical coatings can be eroded by solder. This process can be controlled by the appropriate heat treatment, by the judicious choice of solder alloy or by the use of an underlying film (such as nickel) which has a slow dissolution rate in the solder. Intermetallic phase formation between active solder components such as tin and soluble metallizations such as gold and palladium can result in a loss of strength at elevated temperatures. At temperatures below 100°C, extrapolations predict adequate strenght for reasonable lifetimes.Oxidation is the chief chemical problem in soldering; the solution of this problem is approached by acid treatment before soldering and by flux and/or the use of reducing atmospheres during soldering. Corrosion problems after soldering are controlled by encapsulation with materials such as RTV silicone rubber.Mechanical problems dominate the design of joints to surface-mounted components as well as the terminals connecting film integrated circuits to printed-circuit boards. New terminals feature strain relief, insertion limiters, shank stiffeners and optimized solder distributions. Surface mounting is benefiting from novel methods of solder placement and the use of surface tension forces to support the components away from the substrate. The solder post thus created is comparatively insensitive to thermal expansion mismatch and other shear strains and enables the film circuitry to be places under the surface-mounted component. In this technique it is crucial to maintain a high surface tension during soldering to prevent collapse of the posts.