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The combination of brequinar and
2019-10-03
The combination of brequinar and 5-fluorouracil (5-FU) has been evaluated to assess whether brequinar-induced uridine depletion would improve 5-FU activity. In cells, 5-FU is metabolized into FdUMP and inhibits thymidylate synthetase, which catalyzes the formation of thymidine monophosphate from deo
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To study the effect of DDR inhibition by imatinib
2019-10-02
To study the effect of DDR inhibition by imatinib, nilotinib and dasatinib in a cellular environment we generated DDR1 and DDR2 expressing HEK293 cell lines by stable transfection. Of the five DDR1 splice variants we focused on the 1b variant whose over-expression has been associated with pulmonary
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The host virus coexistence is completely dependent on the ba
2019-10-02
The host-virus coexistence is completely dependent on the balance between a strong immune response inhibiting virus replication and immune evasion and survival of the virus with periodic shedding to enable transmission to new hosts. In the process of ensuring this balance, the virus manipulates 7TM
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The structure of the HOIP
2019-10-02
The structure of the HOIP RBR–LDD module bound to UbcH5~Ub reveals insights into an activated HOIP component [47]. Contacts between the E2~Ub and the non-cognate RBR module in the crystal suggest how a structure in which the active sites of the E2 and the E3 are in close proximity might look. In thi
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br Results To understand how Rad functions to
2019-10-02
Results To understand how Rad53 functions to maintain replisome integrity, we first analyzed newly synthesized leading- and lagging-strand DNA in wild-type (WT) and rad53-1 mutant cells using BrdU-IP-ssSeq, a method that detects synthesis of both leading and lagging strands (Yu et al., 2014). Bri
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Next the BE obtained for the different complexes
2019-10-02
Next, the BE obtained for the different complexes were evaluated. From the BE obtained from our MD simulations, a very good binder can be differentiated from a very weak binder (−11.85 kcal/mol for MTX vs. −6.74 and −3.61 kcal/mol for compounds 14b and 15c, respectively) but ligands with similar bin
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Real time PCR as described previously with
2019-10-02
Real-time PCR, as described previously with minor modifications, was used to detect DNA . The PCR mixture (Qiagen) was as follows: 5mM MgCl2, 2.5μl of 10x PCR Buffer, 0.125μl of HotStarTaq DNA Polymerase, 0.25mM of each dNTP, 0.4μM of each primer and 0.1μM of FAMlabelled probe (‘5-aacaattggagggcaag
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Six substrate recognition sites SRS SRS have been identified
2019-10-02
Six substrate recognition sites (SRS1-SRS6) have been identified at positions 102-123, 204-209, 238-244, 301-319, 374-382 and 483-492 (Table 2, underlined residues) based on Gotoh\'s proposal [30]. CYP3A163 displays the similar characteristic long sequences between helices F and G presenting two add
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br Acknowledgments This research was
2019-10-02
Acknowledgments This research was supported by grants from the Ministerio de Ciencia e Innovación (Grants SAF/FEDER 2010-17907; 2013-49076-P), Spain, Red de trastornos adictivos (RETICS RD12/0028//0003, Instituto de Salud Carlos III, Spain) and Fundación Séneca (15405/PI/10, Región de Murcia, Spa
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In this study a GMI of was associated
2019-10-02
In this study, a GMI of 1.0 was associated with high sensitivity above 90%, specificity below 30% and higher negative predictive value. However, this cut-off couldn\'t have been optimal because of the lower level of Youden J Index which was detected in sputum than in other respiratory fluids (Kimur
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Models and theories The CPA equation of
2019-10-02
Models and theories The CPA equation of state is composed predominantly of two parts: physical item and the association item based on the thermodynamic perturbation theory [21], [22], [26], [27]. The physical item is used to represent intermolecular physical interaction, usually representing the SR
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Antioxidants such as SFN have been proposed to be chemopreve
2019-10-02
Antioxidants such as SFN have been proposed to be chemopreventive agents to inhibit, delay or reverse the development of cancer (Bayat Mokhtari et al., 2018). SFN was shown in breast epithelial cell culture to suppress oxidative metabolism of E2/E1 and thus protect against estrogen-mediated DNA dama
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Gastrointestinal tone can be effectively modulated by cholin
2019-10-02
Gastrointestinal tone can be effectively modulated by cholinesterase inhibitors. As parasympathetic fibers release kynurenine pathway to contract the circular and longitudinal intestinal muscles, AChE inhibition can facilitate those actions. Postoperative ileus (delayed gastric emptying after surge
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br ET Antagonist for the Future Macitentan
2019-10-02
ET Antagonist for the Future: Macitentan and Atresentan Macitentan is an insurmountable antagonist, resulting from structure-activity studies to improve the efficacy and tolerability of bosentan, and gained approval in the United States in 2013 for the treatment of PAH. Actelion describes the com
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Why then is leading strand DNA synthesis
2019-10-01
Why then is leading-strand DNA synthesis reduced relative to lagging-strand synthesis in rad53-1 mutant rna polymerase under replication stress? To gain insight into this question, we first determined whether the firing of late origins in rad53-1 mutant cells contributes to compromised leading-stra
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