Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system.
(49/779)
Activation of prodrugs by Escherichia coli purine nucleoside phosphorylase (PNP) provides a method for selectively killing tumor cells expressing a transfected PNP gene. This gene therapy approach requires matching a prodrug and a known enzymatic activity present only in tumor cells. The specificity of the method relies on avoiding prodrug cleavage by enzymes already present in the host cells or the intestinal flora. Using crystallographic and computer modeling methods as guides, we have redesigned E. coli PNP to cleave new prodrug substrates more efficiently than does the wild-type enzyme. In particular, the M64V PNP mutant cleaves 9-(6-deoxy-alpha-L-talofuranosyl)-6-methylpurine with a kcat/Km over 100 times greater than for native E. coli PNP. In a xenograft tumor experiment, this compound caused regression of tumors expressing the M64V PNP gene. (+info)
Advances in modeling of biomolecular interactions.
(50/779)
Modeling of molecular interactions is increasingly used in life science research and biotechnology development. Examples are computer aided drug design, prediction of protein interactions with other molecules, and simulation of networks of biomolecules in a particular process in human body. This article reviews recent progress in the related fields and provides a brief overview on the methods used in molecular modeling of biological systems. (+info)
ROSO: optimizing oligonucleotide probes for microarrays.
(51/779)
ROSO is software to design optimal oligonucleotide probe sets for microarrays. Selected probes show no significant cross-hybridization, no stable secondary structures and their Tm are chosen to minimize the Tm variability of the probe set. AVAILABILITY: The program is available on the internet. Sources are freely available, for non-profit use, on request to the authors. SUPPLEMENTARY INFORMATION: http://pbil.univ-lyon1.fr/roso (+info)
Application of rapid prototyping to operative dentistry curriculum.
(52/779)
Computers are becoming an integral part of dental education and dental practice. Rapid prototyping is a technique for the production of solid objects from computer models. The variety of rapid prototyping devices and materials that can be processed is increasing all the time. In this article, the authors present a discriminative learning device and associated exercises for developing visual recognition skills and examine the potential for the application of rapid prototyping to the operative dentistry curriculum. Other rapid prototyping technologies as applied in dentistry are also discussed. (+info)
Gene specific siRNA selector.
(53/779)
Small interfering RNA (siRNA) is used in functional genomics applications to decrease the expression of a target gene, which may yield a biological effect that suggests a function for the target gene. The siRNA design tool scans a target gene for candidate siRNA sequences that satisfy user-adjustable rules. Selected candidates are then screened to identify those siRNA sequences that are specific to the gene of interest. (+info)
Bivalent tethering of SspB to ClpXP is required for efficient substrate delivery: a protein-design study.
(54/779)
SspB homodimers deliver ssrA-tagged substrates to ClpXP for degradation. SspB consists of a substrate binding domain and an unstructured tail with a ClpX binding module (XB). Using computational design, we engineered an SspB heterodimer whose subunits did not form homodimers. Experiments with the designed molecule and variants lacking one or two tails demonstrate that both XB modules are required for strong binding and efficient substrate delivery to ClpXP. Assembly of stable SspB-substrate-ClpX delivery complexes requires the coupling of weak tethering interactions between ClpX and the SspB XB modules as well as interactions between ClpX and the substrate degradation tag. The ClpX hexamer contains three XB binding sites, one per N domain dimer, and thus binds strongly to just one SspB dimer at a time. Because different adaptor proteins use the same tethering sites in ClpX, those which employ bivalent tethering, like SspB, will compete more effectively for substrate delivery to ClpXP. (+info)
A Web-based design center for vector-based siRNA and siRNA cassette.
(55/779)
SUMMARY: To facilitate the designing process for vector-based siRNA and siRNA cassette, a tool set has been developed consisting of a siRNA target finder, a siRNA construct builder and a siRNA sequence scrambler. The siRNA target finder is used to identify candidate siRNA target sites. The program automates homology filtering, minimizes non-specific cross-reaction, filters target sites based on RNA duplex internal stability and siRNA sense/anti-sense strand secondary structure. The siRNA construct builder is used to create a siRNA hairpin construct as a vector insert or a cassette insert. The siRNA sequence scrambler is used to generate a negative control sequence for siRNA experiments. Together, these programs provide a comprehensive utility set to address the specific bioinformatics need of DNA-based siRNA design. AVAILABILITY: The Web-based design tools are available at GenScript Website (siRNA design center). http://www.genscript.com or http://www.genscript.com/rnai.html#design or http://www.genscript.com/sirna_ca.html#design (+info)
Design and ergonomics. Methods for integrating ergonomics at hand tool design stage.
(56/779)
As a marked increase in the number of musculoskeletal disorders was noted in many industrialized countries and more specifically in companies that require the use of hand tools, the French National Research and Safety Institute (INRS) launched in 1999 a research project on the topic of integrating ergonomics into hand tool design, and more particularly to a design of a boning knife. After a brief recall of the difficulties of integrating ergonomics at the design stage, the present paper shows how 3 design methodological tools--Functional Analysis, Quality Function Deployment and TRIZ--have been applied to the design of a boning knife. Implementation of these tools enabled us to demonstrate the extent to which they are capable of responding to the difficulties of integrating ergonomics into product design. (+info)