Multi-timescale analysis of a metabolic network in synthetic biology: a kinetic model for 3-hydroxypropionic acid production via beta-alanine

A biosustainable production route for 3-hydroxypropionic acid (3HP), an important platform chemical, would allow 3HP to be produced without using fossil fuels. We are interested in investigating a potential biochemical route to 3HP from pyruvate through b -alanine and, in this paper, we develop and solve a mathematical model for the reaction kinetics of the metabolites involved in this pathway. We consider two limiting cases, one where the levels of pyruvate are never replenished, the other where the levels of pyruvate are continuously replenished and thus kept constant. We exploit the natural separation of both the time scales and the metabolite concentrations to make significant asymptotic progress in understanding the system without resorting to computationally expensive parameter sweeps. Using our asymptotic results, we are able to predict the most important reactions to maximize the production of 3HP in this system while reducing the maximum amount of the toxic intermediate compound malonic semialdehyde present at any one time, and thus we are able to recommend which enzymes experimentalists should focus on manipulating

Molecular dynamics simulations of non-equilibrium systems

Peer reviewe

Molecular dynamics simulations of energetic C60 impacts on (2x1)-(100) silicon

Single impacts of energetic C60 clusters on (2×1)-(100) silicon substrates are studied by molecular-dynamics simulations. The role of impact energies and internal cluster energy are investigated in detail. Six different energy regimes can be identified at the end of the ballistic phase: At thermal energies below 20 eV the fullerene cages undergo elastic deformation, while impinging on the surface, and are mostly chemisorpted on top of the (2×1)-dimer rows. Between 20 and 100 eV the cage structure is preserved after the collision, but the cluster comes to rest within a few monolayers of the silicon surface. At energies of 100–500 eV the cluster partially decomposes and small coherent carbon caps are embedded in the surface. At higher energies up to 1.5 keV complete decomposition of the fullerene cluster occurs and an amorphous zone is formed in the subsurface area. At energies greater than approximately 1.5 keV craters form and above 6 keV sputtering becomes significant. In all cases the substrate temperature is of minor influence on the final result, but the projectile temperature is important for impacts at lower energies (<1.5 keV). For high energy impacts the ballistics resemble that of single atom impacts. Nearly 1:1 stoichiometry is obtained for impact energies around 1 keV. These results reveal an interesting possibility for controlled implantation of C in Si at high local concentrations, which might allow the formation of silicon carbide

Molecular-dynamics simulations of energetic {C}-60 impacts on (2x1)-(100) silicon

Single impacts of energetic C60 clusters on (2×1)-(100) silicon substrates are studied by molecular-dynamics simulations. The role of impact energies and internal cluster energy are investigated in detail. Six different energy regimes can be identified at the end of the ballistic phase: At thermal energies below 20 eV the fullerene cages undergo elastic deformation, while impinging on the surface, and are mostly chemisorpted on top of the (2×1)-dimer rows. Between 20 and 100 eV the cage structure is preserved after the collision, but the cluster comes to rest within a few monolayers of the silicon surface. At energies of 100–500 eV the cluster partially decomposes and small coherent carbon caps are embedded in the surface. At higher energies up to 1.5 keV complete decomposition of the fullerene cluster occurs and an amorphous zone is formed in the subsurface area. At energies greater than approximately 1.5 keV craters form and above 6 keV sputtering becomes significant. In all cases the substrate temperature is of minor influence on the final result, but the projectile temperature is important for impacts at lower energies (<1.5 keV). For high energy impacts the ballistics resemble that of single atom impacts. Nearly 1:1 stoichiometry is obtained for impact energies around 1 keV. These results reveal an interesting possibility for controlled implantation of C in Si at high local concentrations, which might allow the formation of silicon carbide

Valeur pronostique de la teneur en ADN des cellules tumorales colo-rectales. [Prognostic value of DNA ploidy of colorectal tumor cells]

The analysis of ploidy provides valuable information allowing a more precise diagnosis, a more dependable prognostic and the choice of appropriate therapy. With ploidy analysis one can assess the aggressiveness of a given tumor. Aneuploidy of tumors clearly indicates a significantly lower patient survival index. Ploidy analysis of tissue sections yields a clear overall indication of the proportion of cells exhibiting hyperploidy within the tumor mass. The application of this approach is amenable to diverse types of tumors including colo-rectal neoplasias. Additionally, it provides a correlation with the histological presentation of each tumor. The study includes DNA ploidy analysis of 212 patients with primary adenocarcinoma. Sixty-four of the cases examined had follow-ups of a least 2 years. Eighteen of this group had diploid non-proliferating tumors, of which 2 (11%) subsequently died. Nineteen of the 64 had proliferating diploid tumors, 11 (58%) of whom died within the follow-up periods. Twenty-seven patients had tumors which were clearly aneuploid, 12 (45%) of whom later died. Our study demonstrates the prognostic value of ploidy analysis. The preliminary results indicate that mortality of patients with proliferating tumors is approximately 50% after 2 years. This prognostic is independent of other more classical criteria of tumor staging, namely Dukes' classification, histological differentiation and size of tumor. In the near future, ploidy analysis should be introduced as a standard part of tumor assessment. It clearly provides a valuable prognostic allowing the selection of patients requiring a careful follow-up

Les controles de qualité externes pour le laboratoire d'allergologie auprès du Centre suisse de contrôle de qualité de 2006 a 2008

External assessment of analytical performance is part of the quality assurance in medical laboratory. These external controls are mandatory in Switzerland since 2006 for IgE analysis. The Swiss Society for Immunology and Allergy and the Swiss external quality centers had launched a program for total IgE, IgE specific for cat epithelium, birch pollen and peanut, and multi-specific IgE. They have set up criteria for proficiency assessment. Analysis of data obtained from 2006 to 2008 in the Quality Control Center Switzerland shows that results are very good for all the methods used and that a large number of participants fulfill the requirements to obtain the certificate of QUALAB conformity

Prognosis in Duke's B colorectal carcinoma: the Jass classification revisited.

OBJECTIVE: To assess whether Jass staging enhances prognostic prediction in Dukes' B colorectal carcinoma. DESIGN: A historical cohort observational study. SETTING: A university tertiary care centre, Switzerland. SUBJECTS: 108 consecutive patients. INTERVENTIONS: Curative resection of Dukes' B colorectal carcinoma between January 1985 and December 1988, Patients with familial adenomatous polyposis; hereditary non-polyposis colorectal cancer; Crohns' disease; ulcerative colitis and synchronous and recurrent tumours were excluded. A comparable group of 155 consecutive patients with Dukes' C carcinoma were included for reference purposes. MAIN OUTCOME MEASURES: Disease free and overall survival for Dukes' B and overall survival for Dukes' C tumours. RESULTS: Dukes' B tumours in Jass group III or with an infiltrated margin had a significantly worse disease-free survival (p = 0.001 and 0.0001, respectively) and those with infiltrated margins had a significantly worse overall survival (p = 0.002). Overall survival among those with Dukes' B Jass III and Dukes' B with infiltrated margins was no better than overall survival among all patients with Dukes' C tumours. CONCLUSION: Jass staging and the nature of the margin of invasion allow patients undergoing curative surgery for Dukes' B colorectal carcinoma to be separated into prognostic groups. A group of patients with Dukes' B tumours whose prognosis is inseparable from those with Dukes' C tumours can be identified, the nature of the margin of invasion being used to classify a larger number of patients

Metastases hepatiques synchrones de l'adenocarcinome colo-rectal: jusqu'ou aller? A propos de 36 cas. [Synchronous hepatic metastases of colorectal adenocarcinoma: what is the course? Apropos of 36 cases]

The discovery of synchronous hepatic metastases from colorectal cancer poses a tactical problem ticklish to resolve. What are favourable circumstances for curative excision of hepatic metastases? When and how to operate them? To try to respond, we analysed a collective of 36 patients between 10. 1. 1985 and 30. 12. 1986. Of the patients staged Dukes B presenting synchronous hepatic metastases (less than 4, less than 50% of hepatic involvement by the tumour) without systemic involvement, excision at the first attempt is realizable and will be a benefit for the patient. For the others, excision is to be considered in the near future after having analysed (tumour grading and staging, CEA, ploidy of primary tumour). Patients presenting extrahepatic metastases will not benefit from hepatic resection. Surgery, associated or not to regional infusion chemotherapy is discussed