Common Chemical Inductors of Replication Stress: Focus on Cell-Based Studies.

DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS). Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research. These compounds act on replication by direct interaction with DNA causing DNA crosslinks and bulky lesions (cisplatin), chemical interference with the metabolism of deoxyribonucleotide triphosphates (hydroxyurea), direct inhibition of the activity of replicative DNA polymerases (aphidicolin) and interference with enzymes dealing with topological DNA stress (camptothecin, etoposide). As a variety of mechanisms can induce RS, the responses of mammalian cells also vary. Here, we review the activity and mechanism of action of these compounds based on recent knowledge, accompanied by examples of induced phenotypes, cellular readouts and commonly used doses

EIN NEUES OPTISCHES MESSGERÄT ZUR MESSUNG DER GERADHEIT LANGER BOHRUNGEN

The measurement of workpieces with long but smalldiametric cavitys (drills) is always a difficult problem. The apparatus shown in this paper has been developped for measurement of the straightness of cavitys with 5-10 mm diameter and 600-1000 mm length. The optical principle of this measuring allows to achieve the uncertainty less then ± 5 11 qm

Challenges And Factors Associated With Poor Glycemic Control Among Type 2 Diabetes Mellitus Patients At Nekemte Referral Hospital, Western Ethiopia.

Background: Diabetes is increasing at an alarming rate throughout the world, and ~80% of diabetics live in developing countries. Similar to the rest of sub-Saharan African countries, Ethiopia is experiencing a significant burden of diabetes, with increased prevalence, complications, and mortality, as well as life threatening disabilities. Reasons for poor glycemic control among type 2 diabetes patients are complex and multivariable. Hence, this study aimed to identify challenges and factors associated with poor glycemic control among type 2 diabetes patients. Method: A hospital-based cross-sectional study was conducted among type 2 diabetic patients attending the diabetic clinic of Nekemte Referral Hospital (NRH) from February 1 to April 30, 2018. Fasting blood glucose levels of the last three clinic visits were obtained and the mean fasting blood glucose measurement was used to determine the level of glycemic control. Analysis included both descriptive and inferential statistics with SPSS version 20.0. Predictor variable P10 years) (AOR=3.94, 95% CI=1.51-27.83, P=0.012), inadequate physical exercise (AOR=3.19, 95% CI=1.05-19.84, P=0.019), and smoking (AOR=4.51, 95% CI=0.00-0.50, P=0.022) were independent predictors of poor glycemic control on multivariable logistic regression analysis. Conclusion: Nearly two-thirds of patients had poorly controlled diabetes. Age, exercise, level of education, duration of the treatment, and smoking were significantly associated with poor glycemic control. Health facilities should provide continuous education, and barriers of glycemic control should be explored with further research

Review of Hardware for PTCA

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72432/1/j.1540-8183.1988.tb00408.x.pd

Comparing 2-nt 3\u27 Overhangs Against Blunt-Ended siRNAs: A Systems Biology Based Study

In this study, we formulate a computational reaction model following a chemical kinetic theory approach to predict the binding rate constant for the siRNA-RISC complex formation reaction. The model allowed us to study the potency difference between 2-nt 3\u27 overhangs against blunt-ended siRNA molecules in an RNA interference (RNAi) system. The rate constant predicted by this model was fed into a stochastic simulation of the RNAi system (using the Gillespie stochastic simulator) to study the overall potency effect. We observed that the stochasticity in the transcription/translation machinery has no observable effects in the RNAi pathway. Sustained gene silencing using siRNAs can be achieved only if there is a way to replenish the dsRNA molecules in the cell. Initial findings show about 1.5 times more blunt-ended molecules will be required to keep the mRNA at the same reduced level compared to the 2-nt overhang siRNAs. However, the mRNA levels jump back to saturation after a longer time when blunt-ended siRNAs are used. We found that the siRNA-RISC complex formation reaction rate was 2 times slower when blunt-ended molecules were used pointing to the fact that the presence of the 2-nt overhangs has a greater effect on the reaction in which the bound RISC complex cleaves the mRNA

Comparing 2-nt 3' overhangs against blunt-ended siRNAs: a systems biology based study

In this study, we formulate a computational reaction model following a chemical kinetic theory approach to predict the binding rate constant for the siRNA-RISC complex formation reaction. The model allowed us to study the potency difference between 2-nt 3' overhangs against blunt-ended siRNA molecules in an RNA interference (RNAi) system. The rate constant predicted by this model was fed into a stochastic simulation of the RNAi system (using the Gillespie stochastic simulator) to study the overall potency effect. We observed that the stochasticity in the transcription/translation machinery has no observable effects in the RNAi pathway. Sustained gene silencing using siRNAs can be achieved only if there is a way to replenish the dsRNA molecules in the cell. Initial findings show about 1.5 times more blunt-ended molecules will be required to keep the mRNA at the same reduced level compared to the 2-nt overhang siRNAs. However, the mRNA levels jump back to saturation after a longer time when blunt-ended siRNAs are used. We found that the siRNA-RISC complex formation reaction rate was 2 times slower when blunt-ended molecules were used pointing to the fact that the presence of the 2-nt overhangs has a greater effect on the reaction in which the bound RISC complex cleaves the mRNA

Thermo-mechanical analysis of dental silicone polymers

Soft lining materials are used to replace the inner surface of a conventional complete denture, especially for weak elderly patients, with delicate health who cannot tolerate the hard acrylic denture base. Most of these patients have fragile supporting mucosa, excessive residual ridge resorption, particularly on the mandibular arch. The application of a soft liner to the mandibular denture allows absorbing impact forces during mastication and relieving oral mucosa. Actually, the silicone rubbers constitute the main family of commercialised soft lining materials. This study was conducted to understand the relationships between the mechanical properties and the physical structure of polysiloxanes. For this purpose, a series of polysiloxanes of various chemical compositions have been investigated. The evolution of their physical structure as a function of temperature has been followed by differential scanning calorimetry (DSC). In order to facilitate comparisons, the mechanical modulus has been analysed upon the same heating rate using dynamic mechanical analysis (DMA). Polysiloxanes actually commercialised as soft denture liners are three-dimensional networks: the flexibility of chains allows a crystalline organisation in an amorphous phase leading to the low value of the shear modulus. The dynamic mechanical analysis shows that they are used in the rubbery state. So, polysiloxanes have steady mechanical properties during physiological utilisation