Industries like telecommunications, medical, automotive, military, avionics, and aerospace use complex real-time systems. Specification Description Language (SDL) is one of the leading domain specific languages that formally defined by international standards well established in describing such To check system properties abstracted model prepared selected modeling language. We Spin (Simple Prom...

The kinetics of the reaction catalyzed by thymidylate synthase from Lactobacillus casei were investigated at pH 6.8 and 30” with the natural isomer of 5,10-methylene5,6,7&tetrahydrofolate ((+)-CH,-H,folate). An apparatus for adding the enzyme to the reaction mixture and rapidly mixing without opening the sample compartment allowed the acquisition of spectrophotometric rate data within a few sec...

In humans de novo synthesis of 2'-deoxythymidine-5'-monophosphate (dTMP), an essential building block of DNA, utilizes an enzymatic pathway requiring thymidylate synthase (TSase) and dihydrofolate reductase (DHFR). The enzyme flavin-dependent thymidylate synthase (FDTS) represents an alternative enzymatic pathway to synthesize dTMP, which is not present in human cells. A number of pathogenic ba...

Human mutations in MTHFD1 have recently been identified in patients with severe combined immunodeficiency (SCID). SCID results from inborn errors of metabolism that cause impaired T- and B-cell proliferation and function. One of the most common causes of SCID is adenosine deaminase (ADA) deficiency, which ultimately inhibits DNA synthesis and cell division. MTHFD1 has been shown to translocate ...

FAUST is a software tool that generates formal abstractions of (possibly non-deterministic) discrete-time Markov processes (dtMP) defined over uncountable (continuous) state spaces. A dtMP model (Sec. 1) is specified in MATLAB and abstracted as a finite-state Markov chain or Markov decision processes. The abstraction procedure (Sec. 2) runs in MATLAB and employs parallel computations and fast m...

In this study, A2780 human ovarian carcinoma cells were grown in folinic acid in contrast to folic acid, and the molecular and biochemical properties of cisplatin-resistant A2780 cells were analyzed for changes in the dTMP synthase cycle. At concentrations of folinic acid that were optimal for cell growth (10(-8) M), the ED50 for cisplatin was 2.5 and 43 microM in the A2780S and A2780DDP cells,...

The deoxythymidylate phosphohydrolase (dTMPase) induced by Bacillus subtilis bacteriophage PBS2 (whose DNA contains uracil instead of thymine) has been partially purified and shown to possess deoxyuridylate phosphohydrolase (dUMPase) activity. The similarities of induction period, pH dependence, heat and trypsin inactivation, sulfhydryl reagent and fluoride inhibition, metal ion effects, kineti...

3’-Azido-3’-deoxythymidine 5’4riphosphate (AZTTP) was an efficient substrate for the human immunodeficiency virus 1 reverse transcriptase. It was incorporated into both homopolymer and defined sequence DNA-primed RNA templates and DNA-primed DNA templates. The substrate and inhibitor kinetics of both AZTTP and dTTP were dependent on the template-primer and reaction conditions used. dTMP was inc...

The influence of nine newly synthesized uracil acyclonucleosides, and 36 derivatives of 1,2,3,4-tetrahydroisoquinoline on the activity of enzymes catalysing dTMP and dGMP synthesis, on the content of dTTP and dGTP in acid soluble fraction and on the incorporation of [14C]dThd and [14C ]dGuo into DNA in tumour homogenates was studied. The influence of the compounds was studied in the cytosol fro...