Balancing with diversity

Stocks, M. J., Wilden, G. R. H, Pairaudeau, G., Perry, M. W. D, Steele, J., Stone-hous, J. P. (2009) A practical method for targeted library design balancing lead-like properties with diversity. ChemMedChem 4, 800-808. 

Polyoxometalates (POMs), also known as heteropolyacids (HPA),3 are a class of compounds formed from negatively charged inorganic metal-oxygen building blocks. When charge-balanced with cationic species, POMs self-assemble into unusual 3D structures with specific topological and electronic properties.214 POMs are commonly formed from polyanions of early transition metals such as W, Mo or V. These anions can be substituted with other transition metals. The diversities in POMs composition and structure make them attractive for many applications, particularly as Bronsted acid and redox catalysts. For example,... 

Once the PKSs are expressed and modified, the enzymes will require a suitable pool of primer and extender units. As noted previously, these substrates can exist over a broad range - one of the important elements that leads to the diversity of poly-ketide molecules. Thus, an effective heterologous host must be able to synthesize a range of substrates at a level that insures availability when needed, but that is also balanced with other metabolite pools. While this necessity sounds daunting, it is the case that not all polyketide products require the use of every variation of primer and extender unit. In fact, many polyke-tides are derived from a subset of acetyl-GoA, propionyl-GoA, malonyl-GoA, and methylmalonyl-GoA alone. Thus, a host that can produce just these four substrates would be suitable for the production of many polyketides. 

Combinatorial chemistry has become one of the main tools for the rapid construction of molecular libraries for use in drug discovery and in biology. Important factors for the design of these libraries are structural diversity and complexity, which have to be balanced with size and purity of the individual compounds. For the construction of these libraries, solid phase chemistry has become a basic technique... 

Personalities. The Roundtable is foremost a process—a process for bringing together the diverse constituencies concerned with the research enterprise. The ability of the Roundtable to stimulate constructive change in the system depends on the "delicacy and the balance with which it is able to address issues that are typically complex, intractable, and controversial. As such it is an intensely personal enterprise, whose effectiveness has depended on the ability of the Roundtable Chairman, the Council, the Working Groups, and the staff to work constructively with the full range of relevant constituency groups and individuals. 

The demand chain has been a near mirror image of the supply chain. It has been driven by a business competitive imperative aiming to constantly improve its supply chain efficiencies. The demand chain must balance aglobally diverse mix of new customers (each with different needs and expectations), and it must also offer a degree of uniqueness to the business (Bariow-Hills Sarin, 2003). 

The development project shall be governed by an organization with good safety culture, where safety is the highest priority. Processes provide adequate and independent checks and balances, intellectual diversity is sought in all processes and that a defined, documented, disciplined process is followed at all levels. 

The Kona Conference and many other events that I could cite show that it is now time to end this compartmentalization of knowledge, get our act together, and understand that there is a common body of concepts and techniques that apply to a large domain of very important processes and situations. Professor Doraiswami Ramkrishna has made a major contribution to the needed unification of theory and computational techniques of population balances with the preparation of his book Population Balances Theory and Applications to Particulate Systems in Engineering. It should be, and I hope it will be, the source that workers from many diverse fields turn to when they seek to learn the concepts and techniques of population balance modeling of particulate systems. 

Prebiotics, polyunsaturated fatty acids (PUFAs) and phytochemicals are the most well characterized dietary bioactive compounds. The beneficial effects of prebiotics mainly relay on their influence on the gut microbiota composition and their ability to generate fermentation products (short-chain fatty acids) with diverse biological roles (Laparra and Sanz 2010). PUFAs include the co3 and co6 fatty acids, whose balance may influence diverse aspects of immunity and metabolism. 

So why focus on VBP Earlier we argued that the classic image of publicly supported fundamental science and private support for more applied work is not useful. Innovation emerges from a more diverse and complicated patterns of interactions between private and public sectors that work across the R D and product development processes to create new medicines and make them accessible to patients. The public sector has to intervene in multiple ways to ensure that incentives offered for drug development are balanced with broad public interest agendas in ensuring access to medicines in response to need. 

As the number of conformations increases exponentially with the number of rotatable bonds, for most molecules it is not feasible to take all possible conformations into account. However, a balanced sampling of the conformational space should be ensured if only subsets arc being considered. In order to restrict the number of geometries output, while retaining a maximum of conformational diversity, ROTATE offers the possibility of classifying the remaining conformations, i.c., similar conformations can be combined into classes. The classification is based on the RMS deviation between the conformations, either in Cartesian (RMS y 7if [A]) or torsion space in [ ], The RMS threshold, which decides whether two... 

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