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bigbio

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hallmarks_of_cancer

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12101

23089335_11

Although demographic characteristics distinguished all trajectory classes , adverse health characteristics distinguished the overweight and obese classes from the normal-weight class , but not from each other .

12102

23089335_12

Problems associated with education and health are present at study entry and should be addressed earlier in life .

12103

22947917_0

Molecular dynamics ( MD ) simulations of the single-stranded DNA trinucleotide TG*G* , with the G* guanines crosslinked by the antitumor drug cisplatin , were performed with explicit representation of the water as solvent .

12104

22947917_1

The purpose of the simulations was to explain previous NMR observations indicating that in single-stranded cisplatin-DNA adducts , the crosslinked guanines adopt a left-handed helical orientation , whereas in duplexes , the orientation is right-handed .

12105

22947917_2

The analysis of the MD trajectory of TG*G* has ascribed a crucial role to hydrogen-bonding ( direct or through-water ) interactions of the 5'-oriented NH(3) ligand of platinum with acceptor groups at the 5'-side of the crosslink , namely the TpG* phosphate and the terminal 5'-OH group .

12106

22947917_3

These interactions bring about some strain into the trinucleotide which is slightly but significantly ( 1-1.5 kcal.mol(-1) ) higher for the right-handed orientation than for the left-handed one .

12107

22947917_4

During the unconstrained , 3 ns long MD simulation , left-handed conformations were times more abundant than the right-handed ones .

12108

22947917_5

This sampling difference agrees roughly with the calculated energy difference in strain energy .

12109

22947917_6

Overall , these results show that the Pt-GG crosslink within single-stranded DNA is malleable and can access different conformations at a moderate energy cost .

12110

22947917_7

This malleability could be of importance in interactions between the platinated DNA and cellular proteins , in which the DNA is locally unwound .

12111

12549857_0

An in vitro angiogenesis system was designed for screening angiogenic agonists and antagonists .

12112

12549857_1

In order to obtain large quantities of cells and reproducibility , human endothelial cells with extended life spans were developed by retroviral transfection .

12113

12549857_2

The resulting cells grown in a serum-free medium containing endothelial cell growth supplement ( ECGS ) have a telomerase activity , extended life spans of at least 21 passages , and an endothelial cell phenotype ( diI-acetylated-LDL upake , factor VIII-related antigen , VEGFR-1 and R-2 , and tissue-type plasminogen activator ( tPA) ) that resembled that of unaltered primary endothelial cells .

12114

12549857_3

Exceptions were ( i ) a higher expression of tPA , and ( ii ) a non-significant growth response to FGF-2 or VEGF stimulation .

12115

12549857_4

Within three-dimensional fibrin gels , specific cell clones rapidly formed tubular structures in a more reproducible manner than those observed with low-passage primary cells .

12116

12549857_5

Tube formation by primary endothelial cells and those with extended life spans was dependent upon FGF-2 and ECGS , respectively .

12117

12549857_6

Both cell types produced FGF-2 and VEGF cytokines .

12118

12549857_7

Increasing doses of suramin significantly decreased the size of microvessels formed by both cell lines .

12119

12549857_8

These functional results indicate that a vascular matrix system containing human cells with extended life spans can be successfully utilized as an in vitro assay for antiangiogenic compounds .