The transcription factor HNF3 and linker histones H1 and H5 possess winged-helix DNA-binding domains, yet HNF3 and other fork head-related proteins activate genes during development whereas linker histones compact DNA in chromatin and repress gene expression. We compared how the two classes of factors interact with chromatin templates and found that HNF3 binds DNA at the side of nucleosome cores, similarly to what has been reported for linker histone. A nucleosome structural binding site for HNF3 is occupied at the albumin transcriptional enhancer in active and potentially active chromatin, but not in inactive chromatin in vivo. While wild-type HNF3 protein does not compact DNA extending from the nucleosome, as does linker histone, site-directed mutants of HNF3 can compact nucleosomal DNA if they contain basic amino acids at positions previously shown to be essential for nucleosomal DNA compaction by linker histones. The results illustrate how transcription factors can possess special nucleosome-binding activities that are not predicted from studies of factor interactions with free DNA.

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This article presents the theory behind modern evaluative bibliometric techniques at three levels. Policy applications, which characterizes the scientific and technological output of nations or regions; strategic analyses, which deals with articles and patents at the level of a university or company; and tactical analyses, which addresses questions concerning a single subject. The article explains the newer techniques that have been developed at each level, as well as the more important limitations.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that downregulates low-density lipoprotein (LDL) receptor (LDL-R) levels on the surface of hepatocytes, resulting in decreased clearance of LDL-cholesterol (LDL-C). Phenotypic screening of a small-molecule compound collection was used to identify an inhibitor of PCSK9 secretion, (R)-N-(isoquinolin-1-yl)-3-(4-methoxyphenyl)-N-(piperidin-3-yl)propanamide (R-IMPP), which was shown to stimulate uptake of LDL-C in hepatoma cells by increasing LDL-R levels, without altering levels of secreted transferrin. Systematic investigation of the mode of action revealed that R-IMPP did not decrease PCSK9 transcription or increase PCSK9 degradation, but instead caused transcript-dependent inhibition of PCSK9 translation. In support of this surprising mechanism of action, we found that R-IMPP was able to selectively bind to human, but not E. coli, ribosomes. This study opens a new avenue for the development of drugs that modulate the activity of target proteins by mechanisms involving inhibition of eukaryotic translation.

Accurate models for condensation heat transfer are necessary to improve condenser design. Drop-size distribution is an important aspect of heat transfer modeling that is difficult to measure for small drop sizes. The present work uses a numerical simulation of condensation which incorporates the possibility of coalescence and coalescenceinduced jumping over a range of drop sizes. Results of the simulation are compared with previous theoretical models and the impact of the assumptions used in those models is explored. In particular, previous drop-size distribution models may predict heat transfer rates less accurately for high contact angles and for coalescence-induced jumping since coalescence occurs over a range of drop sizes and does not always result in departure. The influence of various input parameters (nucleation site distribution approach, nucleation site density, contact angle, maximum drop size, heat transfer modeling to individual drops, and minimum jumping size) on the drop-size distribution and overall heat transfer rate is explored. Assignment of the nucleation site spatial distribution and heat transfer model affect both the drop-size distribution and predicted overall heat transfer rate. Results from the simulation suggest that, when the contact angle is large (as on superhydrophobic surfaces) and no coalescence-induced jumping occurs, the heat transfer may not be as sensitive to the maximum drop-size as previously supposed. Furthermore, this work suggests that when coalescenceinduced jumping occurs, reducing the maximum drop size may not always increase heat transfer since drops similar in size to those removed by coalescence-induced jumping can contribute significantly to the overall heat transfer rate.