Downstream collaboration

In the development of new products, optimization of the fermentation medium for titer only often ignores the consequences of the medium properties on subsequent downstream processing steps such as filtration and chromatography. It is imperative, therefore, that there be effective communication and understanding between workers on the upstream and downstream phases of the produc t development if rational trade-offs are to be made to ensure overall optimahty of the process. One example is to make the conscious decision, in collaboration with those responsible for the downstream operations, whether to produce a protein in an unfolded form or in its native folded form the purification of the aggregated unfolded proteins is simpler than that of the native protein, but the refolding process itself to obtain the product in its final form may lack scalabihty. 

Thus DMBA is an initiator, a potent mutagen. TPA is a promoter, and it appears to act by mimicking the signaling molecule diacylglycerol, which activates PKC- a. PKC stimulates transcription of several signaling pathways involving NF-k, MAPK, and AP-1. The downstream effectors of PKC collaborate with the H-ras oncogene in some way to stimulate proliferation of the initiated cells. It is not clear why only the initiated cells are stimulated to yield a clone of initiated cells. 

A collaborative study on the Human and Environmental Risk Assessment (HERA) of cleaning products between Cefic and the International Soap, Detergent and Maintenance Products Association (AISE) resulted in the risk assessment of several substances through the relevant supply chains. The project enabled downstream users to develop a better understanding of the final use and environmental endpoints of these products. A major result of the initiative has been the creation of a website where customers and consumers can be informed on the risks associated with specific substances. 

Another important mechanism for promoting programmed cell death is the binding of ligands to the death receptors, which occurs in the extrinsic pathway (8) (Fig. 1). The death receptors recruit and activate caspase-8, which in turn regulates effector caspase-3 and caspase-7. Caspase-8 processes the Bcl-2 family member Bid, which collaborates with other members of the Bcl-2 family to induce cytochrome c release from the mitochondria and thereby activates the downstream intrinsic pathway (9). 

The Institute develops partnerships with organizations representing the interests of the nickel-producing industry s downstream customers and other parts of the nickel life-cycle. The Institute also collaborates with regional and local metals industry organizations. 

Leverage-companies (i.e., purchasers or retailers) demanding upstream and downstream supply chain collaboration on greening initiatives. 

Work in partnership with upstream suppliers and downstream chemical users to collaborate on improved processes for the safe and effective uses of chemicals. 

Toshiba, in collaboration with Tokyo Electric Power Company, has developed a hybrid catalytic combustion. Here only a part of the fuel is converted heterogeneously on the catalyst. The system consists of a pre-combustion mixing zone, a low-temperature catalyst zone, and a gas-phase combustion zone. The fuel-air mixture is controlled to maintain the temperature of the catalyst below 800 C, because the catalyst is not stable above the temperature. More fuel is added downstream to attain the final combustion temperature. The function of the catalyst is to be a source of additional "pre-heat" to support the lean, homogeneous down-stream combustion. 

It is, of course, unacceptable to bind together all manner of development reports and send them over with a cover memorandum (part of what is aptly known as over the fence technology transfer). Attachments are very important, but a well-edited document that is rich in content and aimed at guiding the downstream practitioners is the indispensable first vehicle for the transfer of the know-how. Not even the most thorough collaboration between development and manufacturing can completely remedy the lack of the above comprehensive process document intended for imparting knowledge. 

Sharing product rollover plans with suppliers is a key way to manage the risks of product transitions. Another way to reduce supply uncertainty downstream is to collaborate in the early phases of product design. 

Few supply chain efforts will not require collaboration with upstream suppliers and downstream customers. After all, this is the essence of SCM. Strategy components include information sharing up and down the chain, new roles for suppliers or distribution channel partners, the role of product and process technology, and trading partner contributions to our own effort. The charter should anticipate the need for this participation, and authorize the team to prepare requirements accordingly. 

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