Remarks and Future Directions

Kitazume, T. Terada, C. Sato, A. Kanamori, 1. Tazawa, M. Iwasaki, and Y. Song. Special appreciation is also extended to Dr. J. Ye for her many helpful contributions. The patience and expert secretarial assistance of Ms. Ann Douglass are also acknowledged. Work in the author s laboratory was supported by the National Institutes of Health Grant AI-09352. 

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Albright, C. F., Orlean, P., and Robbins, P. W., 1989, A 13-amino acid peptide in three yeast glycosyltransferases may be involved in dolichol recognition, Proc. Natl. Acad. Sci. USA 86 7366-7369. 

Despite the advances mentioned above there are still clearly a number of major problems that need to be addressed and that will require significant research. Four major problems that we can cite are the following  

Perhaps the biggest gap in terms of effective models is the capability of simultaneously handling changeovers, inventories and resource constraints. Sequential methods can handle well the first, while discrete time models (e.g., STN, RTN), can handle well the last two. While continuous-time models with global time intervals can theoretically handle all of the three issues, they are at this point still much less efficient than discrete time models, and therefore require further research. 

Despite advances in MILP solution methods, problem size is still a major issue since scheduling problems are known to be NP-hard (i.e., exponential increase of computation time with size in worst case). While effective modeling can help to overcome to some extent the issue of computational efficiency, special solution strategies such as decomposition and aggregation are needed in order to address the ever increasing sizes of real-world problems. 

While short-term scheduling problems are important by themselves, they rarely arise in isolation, but they have to be considered as part of a production planning problem. Thus, the integration and simultaneous optimization of planning and scheduling so as to achieve consistency and optimality remains a major outstanding problem. 

It is hoped that the above points will stimulate further research in the area as it is clear that significant work is still required in this area. 

Solar-hydrogen production via the water-splitting reaction on photocatalyst surfaces is one of the most promising technologies for the generation of energy in a clean and sustainable manner. 

The success of this technology will be determined by the development of efficient photocatalysts that must satisfy very specific semiconducting and electrochemical properties. 

Since the pioneering work by Fujishima and Honda, research has made significant progress in the development of efficient photocatalysts under visible light. From these studies, it is readily apparent that the energy conversion efficiency of water splitting is determined principally by the properties of the semiconductors used as photocatalysts. 

In spite of these progresses, current results still record low efficiencies for visible-light-to-hydrogen conversion (2.5% QY) for practical purposes (10% QY). 

To improve the efficiency of photocatalysts, developments in the future must be based on an understanding of the sophisticated factors that determine the photoactivity of the water-splitting reaction (i) molecular reaction mechanisms involved in the oxidation and reduction of water on photocatalyst surfaces, (ii) structure and defect chemistry of photocatalyst surfaces, and (iii) charge transfer mechanisms between 

Proteomics has significantly contributed to elucidate the molecular mechanisms underlying probiotic actions, revealing that some proteins actually mediate both adaptation and adhesion to the GIT as well as immunomodulation. Of note, many of these proteins are also involved in response mechanisms to industrial stresses. As it is well known that strains adapted to a particular stress usually 

Abou Hachem, M., Andersen, J.M., Barrangou, R., M0ller, M.S., Fredslund, F., Majuinder, A., Ejby, M., Lahtinen, S.J., et al. (2013) Recent insight into oligosaccharide uptake and metabolism in probiotic bacteria. Biocatal Biotransfor 31, 226-235. 

Aebersold, R. and Mann, M. (2003) Mass spectrometry-based proteomics. Nature 422, 198-207. 

Alcantara, C. and Zuniga, M. (2012) Proteomic and transcriptomic analysis of the response to bile stress of Lactobacillus casei BL23. Microbiology 158,1206-1218. 

The author thanks the Canadian Bacterial Diseases Network (Centers of Excellence) for funding. 

STRUCTURE AND BIOLOGICAL INTERACTIONS OF HEPARIN AND HEPARAN SULFATE 

Heparin has been in clinical use for decades, to prevent and cure thromboembolic disease. It is only relatively recently that the molecular mechanisms behind the anticoagulant/antithrombotic effects were elucidated. A previous article on the subject in this series highlighted some major advances in our understanding of these mechanisms, in particular regarding the role of antithrombin (AT) and its interaction with the polysaccharide. These relations can now be explained in molecular detail. A most important development of recent years has been the growing awareness of the ubiquitous distribution, stmctural diversity, and biological importance of heparan sulfate (HS). Formerly by and large an unwanted by-product 

Copyright 2001 by Academic Press. All rights of reproduction in any form reserved. 

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