Phosphorylation of Chk1 by ATM- and Rad3-related (ATR) in Xenopus Egg Extracts Requires Binding of ATRIP to ATR but Not the Stable DNA-binding or Coiled-coil Domains of ATRIP

ATR, a critical regulator of DNA replication and damage checkpoint responses, possesses a binding partner called ATRIP. We have studied the functional properties of Xenopus ATR and ATRIP in incubations with purified components and in frog egg extracts. In purified systems, ATRIP associates with DNA in both RPA-dependent and RPA-independent manners, depending on the composition of the template. However, in egg extracts, only the RPA-dependent mode of binding to DNA can be detected. ATRIP adopts an oligomeric state in egg extracts that depends upon binding to ATR. In addition, ATR and ATRIP are mutually dependent on one another for stable binding to DNA in egg extracts. The ATR-dependent oligomerization of ATRIP does not require an intact coiled-coil domain in ATRIP and does not change in the presence of checkpoint-inducing DNA templates. Egg extracts containing a mutant of ATRIP that cannot bind to ATR are defective in the phosphorylation of Chk1. However, extracts containing mutants of ATRIP lacking stable DNA-binding and coiled-coil domains show no reduction in the phosphorylation of Chk1 in response to defined DNA templates. Furthermore, activation of Chk1 does not depend upon RPA under these conditions. These results suggest that ATRIP must associate with ATR in order for ATR to carry out the phosphorylation of Chk1 effectively. However, this function of ATRIP does not involve its ability to mediate the stable binding of ATR to defined checkpoint-inducing DNA templates in egg extracts, does not require an intact coiled-coil domain, and does not depend on RPA

Numerical Analysis of Saturated Sand Under Dynamic Loads

In this study, the behavior of reclaimed soils including the effects of excess pore water pressure and the loss of strength under dynamic loads or earthquakes are investigated and simulated. The constitutive model based on the disturbed state concept (DSC) is introduced and DSC-DYN2D program is utilized in a numerical analysis. In the laboratory test, quasi-static and cyclic triaxial tests were carried out to determine parameters for the numerical analysis. Field tests were executed in Inchon International Airport with a 10 tons hydraulic hammer. In the field test, the data of dynamic loads and excess pore water pressure were measured using a 3-D geophone and a pressure transducer respectively, The data of field tests showed the accumulation of excess pore water pressure when rapid dynamic loads were applied. Especially, a back-prediction program based on DSC model is developed and verified its accuracy using various parameters from the cyclic triaxial test. As the results of numerical simulation, the predicted trends for excess pore water pressure compare well with the observed data. Based on the result of this research, it is found that the numerical analysis based on the DSC model is compatible to predict the softening behavior of saturated reclaimed soils under dynamic loads

Topically administered bevacizumab had longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in rat corneal neovacularization

<b>AIM:</b> To compare the effect of topically administered and subconjunctivally injected bevacizumab on experimental corneal neovascularization in rats for two weeks after treatment.<b>METHODS:</b> Twenty-eight Sprague-Dawley rats were divided into four groups of 7 animals. Each corneal center of right eye was cauterized with silver/potassium nitrate for 8s. After corneal burning, bevacizumab (12.5mg/mL) was topically administered three times per day (TB group) for two weeks or subconjunctivally injected on days 2 and 4 after cauterization (0.02mL; SB group). As negative controls, rats received 0.9% saline topically three times per day (TS group) or subconjunctivally on days 2 and 4 (0.02mL; SS group). Digital photographs of the cornea were taken 1 and 2 weeks after treatment and analyzed to determine the area of cornea covered by neovascularization as the percentage of corneal neovascularization.<b>RESULTS:</b> One week after treatment, the percentage of corneal neovascularization was significantly lower in the TB and SB groups than in the TS and SS groups (all <i>P</i><0.05). Two weeks after treatment, the percentage of corneal neovascularization was significantly lower in the TB group than in the TS group (<i>P</i><0.05). In all groups, the percentage of neovascularization was decreasing as time passed (all <i>P</i><0.05)<b>CONCLUSION:</b> Topically administered bevacizumab has longer standing anti-angiogenic effect than subconjunctivally injected bevacizumab in corneal neovascularization following chemical injury in rats

Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling

The signal transducer and activator of transcription 3 (STAT3) protein is a major transcription factor involved in many cellular processes, such as cell growth and proliferation, differentiation, migration, and cell death or cell apoptosis. It is activated in response to a variety of extracellular stimuli including cytokines and growth factors. The aberrant activation of STAT3 contributes to several human diseases, particularly cancer. Consequently, STAT3-mediated signaling continues to be extensively studied in order to identify potential targets for the development of new and more effective clinical therapeutics. STAT3 activation can be regulated, either positively or negatively, by different posttranslational mechanisms including serine or tyrosine phosphorylation/dephosphorylation, acetylation, or demethylation. One of the major mechanisms that negatively regulates STAT3 activation is dephosphorylation of the tyrosine residue essential for its activation by protein tyrosine phosphatases (PTPs). There are seven PTPs that have been shown to dephosphorylate STAT3 and, thereby, regulate STAT3 signaling: PTP receptor-type D (PTPRD), PTP receptor-type T (PTPRT), PTP receptor-type K (PTPRK), Src homology region 2 (SH-2) domain-containing phosphatase 1(SHP1), SH-2 domain-containing phosphatase 2 (SHP2), MEG2/PTP non-receptor type 9 (PTPN9), and T-cell PTP (TC-PTP)/PTP non-receptor type 2 (PTPN2). These regulators have great potential as targets for the development of more effective therapies against human disease, including cancer

Fabrication of n-type nanotube transistors with large-work-function electrodes

The authors found experimentally that carbon nanotube field-effect transistors (CNFETs) could exhibit n -type characteristics even though their electrodes consist of a large-work-function metal such as Co. To explain their result, which is contrary to the general belief that CNFETs with large-work-function electrodes always lead to p -type characteristics, ab initio electronic structure calculation for the metal-carbon nanotube junction was performed, which showed that the Fermi level alignment at the junction could sensitively depend on microscopic structures of the metal-carbon nanotube junction. This suggests that deposition method of electrodes as well as the metal type could be utilized to obtain n -type CNFETs.open121

anti-9,10-Di(1-naphth­yl)anthracene pyridine disolvate

In the title compound, C34H22·2C5H5N, there is a crystallographic inversion center in the middle of the anthracene ring system. The dihedral angle between the mean planes of the anthracene and naphthalene ring systems is 83.96 (4)°. The crystal structure is stabilized by weak inter­molecular C—H⋯N and C—H⋯π inter­actions