Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors

The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are predicted to interact selectively with the human DNA quadruplex structure, as a means of specifically inhibiting the action of human telomerase in extending the length of single-stranded telomeric DNA. The anilino substituent at the 9-position of the acridine chromophore is predicted to lie in a third groove of the quadruplex. Calculated relative binding energies predict enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a result of this substituent. The ranking order of energies is in accord with equilibrium binding constants for quadruplex measured by surface plasmon resonance techniques, which also show reduced duplex binding compared with the disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro inhibitory activity against human telomerase, with EC50 values of up to 60 nM.

Improving urban park design: A comparative and analytical study addressing resources available and components necessary to improve the environmental and economic sustainability of urban parks

Urban parks have long been valued for the environmental, social, and economic benefits they provide. Increasingly, parks are also being recognized as features important for sustainable city design. This Capstone Project will identify, compare, analyze, and discuss means for designing sustainable urban parks. Recommendations for designing sustainable urban parks, based on project results, include: 1) ensure park features will support high levels of human activity; 2) use gravel to construct park trails; 3) purchase playground structures made of recycled materials; 4) plant a high number of perennials in flowerbeds and other vegetated areas; 5) plant climate-appropriate plants in vegetated areas; 6) ensure parks have high levels of plant diversity; and 7) develop future studies further exploring sustainable park design.

Organizational design, quality management and competitive advantage in hotels

Purpose – The aim of this study is to examine the relationship between practices of quality management (QM) and the characteristics of organizational design, and QM and competitive advantage. Design/methodology/approach – The study uses a partial least squares approach to test these relationships in 350 hotels in Spain. Findings – The findings show that QM influences specialization, formalization and interdepartmental interactions, and that QM practices influence both cost and differentiation competitive advantage. The results also indicate the importance of QM strategic and operational systems as practices that have a key impact on the characteristics of organizational design. Similarly, the QM operational system is key in the relationship between QM and cost competitive advantage. Finally, the QM operational, information and strategic systems positively influence differentiation competitive advantage. Practical implications – When hotels adopt QM practices, there will be significant changes in a number of organizational variables, including specialization, formalization and interdepartmental interactions. This paper provides empirical evidence that QM practices improve both cost and differentiation competitive advantage in the hotel industry. Originality/value – There has been little research on the effects of QM on organizational design in the hotel industry. The contribution of this paper is that analyze the effects of QM on organizational design and competitive advantage, extending knowledge about these issues in a specific sector.

The location and design of safe and convenient park and ride lots. Final report.

California Department of Transportation, Sacramento

National Accident Sampling System sample design - phases 2 and 3 - executive summary. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

National Accident Sampling System sample design - phases 2 and 3. Volume II: exhibits. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

National Accident Sampling System sample design - phases 2 and 3. Volume I: final technical report.

National Highway Traffic Safety Administration, Washington, D.C.

Development and testing of INTRAS, a microscopic freeway simulation model. Volume 1: program design, parameter calibration and freeway dynamics component development. Final report.

Federal Highway Administration, Office of Research and Development, Washington, D.C.

Evaluation of design analysis procedures and acceptance criteria for roadside hardware. Volume III - evaluating pre-report 230 crash tests. Final report.

Federal Highway Administration, Safety Design Division, McLean, Va.

Evaluation of design analysis procedures and acceptance criteria for roadside hardware. Volume IV - the importance of the occupant risk criteria. Final report.

Federal Highway Administration, Safety Design Division, McLean, Va.

Evaluation of design analysis procedures and acceptance criteria for roadside hardware. Volume V - hazards of the redirected car. Final report.

Federal Highway Administration, Safety Design Division, McLean, Va.