Future Direction

Future efforts in the field of environmental analysis will be focused on several fronts, including analyte enrichment and measurement, on-line and on-site techniques, multi-residue methodology, direct injection of aqueous samples into LC/MS/MS 

Specifically for triazines in water, multi-residue methods incorporating SPE and LC/MS/MS will soon be available that are capable of measuring numerous parent compounds and all their relevant degradates (including the hydroxytriazines) in one analysis. Continued increases in liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API-MS/MS) sensitivity will lead to methods requiring no aqueous sample preparation at all, and portions of water samples will be injected directly into the LC column. The use of SPE and GC or LC coupled with MS and MS/MS systems will also be applied routinely to the analysis of more complex sample matrices such as soil and crop and animal tissues. However, the analyte(s) must first be removed from the sample matrix, and additional research is needed to develop more efficient extraction procedures. Increased selectivity during extraction also simplifies the sample purification requirements prior to injection. Certainly, miniaturization of all aspects of the analysis (sample extraction, purification, and instrumentation) will continue, and some of this may involve SEE, subcritical and microwave extraction, sonication, others or even combinations of these techniques for the initial isolation of the analyte(s) from the bulk of the sample matrix. 

Hassall, The Biochemistry and Uses of Pesticides, second edition, VCH, Weinheim (1990). 

Ashton and A.S. Crafts, The Chemistry and Mode of Action of Herbicides, Wiley, New York (1981). 

Windholz, S. Budavaii, R.F. Blumetti, and E.S. Otterbein (eds.), The Merck Index, tenth edition, Merck, Rahway, NJ (1983). 

Targeted delivery is critical to the success of future NO/donor drug discovery efforts. The goal must be to provide quantities of NO, through local administration 

2 Williams, D. L. H., The Chemistry of Amino, Nitroso, Nitro and Related Groups, Supplement F2, John Wiley Sons, New York 1996, p. 665 

5 Goldman, P., Human Intestinal Microflora in Health and Disease, 

14 Magee, P. N., Montesano, R., Preussman, R., Chemical Carcinogens, Ed. C. W. Searle, ACS Monograph Series 173, American Chemical Society, Washington, DC 1976, Chapter 11 

Many theoretical aspects of MDLC have been studied in the past 20 years and there is no question that future discussions and research along these lines will take place and 

One example of a tree-based separator system is shown below in Fig. 2.8 where the Bethe lattice or Cayley tree is shown (Wilson, 1996). This graph can be expanded to any number of levels and can function with dilferent types of columns and electrophoretic elements. This is not the only graph that can function as a complex multidimensional separator system. But it is an example of something with multiple 

FIGURE 2.8 Separator systems cascaded to form a Bethe lattice or Cayley tree where the point of introduction is the graph vertex 0 and solute can be sampled from any of the outward nodes at position 1, 2, 3, 4, and so on. The sample loops and valves are not shown. 

Abamowitz, M., Stegun, I.A., editors. (1965). Handbook of Mathematical Functions With Formulas, Graphs, and Mathematical Tables. Dover Publications, New York. Bang-Jensen, J., Gutin, G. (2002). Digraphs Theory, Algorithms and Applications. Springer, New York. 

Bushey, M.M., Jorgenson, J.W. (1990). Automated instrumentation for comprehensive two-dimensional high-performance liquid chromatography of proteins. Anal. Chem. 62, 161-167. 

We summarize here what seem at this moment to be the ways in which turnover frequency may vary with fraction exposed. We note, however, that in the figures presenting the results there is often disagreement between studies on a given system concerning the shapes of the curves. Perhaps this discussion will encourage the future experimental resolution of some of these problems. 

Reactions favored by principal crystal planes may be antipathetic, and we think that most systems should be antipathetic for FE 0.5. Thus an explicable behavior is that of the monotonic curve 2 of Fig. 25. 

For FE 0.5, structure insensitivity is conceivable, but we think that curve 1 of Fig. 25 is the expected behavior, with a decrease in TOF for FE 0.5. 

Reactions favored by special sites near edges (B5 sites) may show sympathetic behavior for FE 0.5, but at higher FE antipathetic behavior sets in for electronic reasons and sometimes also for geometric reasons. The result is represented by curve 3 of Fig. 25. 

Through comparison of Fig. 25 with Fig. 1 and experimental curves giving TOF versus FE it is not known whether differences are caused by incomplete understanding or by incomplete experimental results. 

Ancient and current biological process that result in either the production of fossil fuels or biomass, are responsible over 90% of the energy that humans have ever used. All of these processes employ photosynthesis, and it is not unrealistic that natural photosynthesis might be adapted to efficiently produce new forms of stored energy for the future use of mankind besides merely the production of biomass. This review has outlined a number of specific biological and systems challenges that must be addressed to advance science and technology down this path. 

The challenges that we can identify now may in fact not be the only ones that must be faced, so we must be prepared to address new issues as we solve the current 

The authors would tike to acknowledge the support of the Hydrogen, Fuel Cell, and Infrastructure Technology Energy Biosciences and GTL Programs within the US Department of Energy. We would also tike to thank everyone in our laboratory for many helpful discussions, and in particular, Dr. Dan Blake, who provided us with critical information on photobioreactor materials. 

Abdel-Basset, R., and Bader, K. P. 1998. Physiological analysis of the hydrogen gas exchange in cyanobacteria. J. Photochem. Photobiol. B Biol. 43, 146-151. 

a) Adams, M. W. W., Mortenson, L. E., and Chen, J. S. 1981. Hydrogenase. Biochim. Biophys. Acta 594, 105-176. b) Adams, M.W.W. 1990. The structure and mechanism of iron-hydrogenases. Biochim. Biophys. Acta 1020, 115-145. 

Our understanding of the biogeochemistry of nitrification has advanced greatly in the past two decades. The basic patterns of distributions and rates have been discovered and are largely understood in terms of the characteristics of the organisms believed to be responsible for the process and their interactions with other components of the ocean s physical and biological systems. Unpredictable surprise discoveries that change our view of the N cycle are hkely to appear, as they have done in recent years. Nevertheless, there are some avenues of future discovery that are more easily predictable on the basis of current research. 

How do the physiological characteristics of the AOA compare with those of the AOB in terms of substrate affinity, light sensitivity, growth rates, oxygen requirements, N2O production, etc. I.e., are AOA and AOB regulated in the environment by similar factors  

The discovery of AOA does not change the magnitude or distribution of nitrification rates. It may that AOA, rather than AOB, are predominantly responsible for the measured rates, but that does not alter the rates. Thus the in situ abundance and activities of AOA, when determined, must be compatible with the biogeochemical constraints discussed above. 

Are NO A waiting to be discovered Even less is known about the abundance and growth characteristics of important marine NOB than the AOB it is entirely possible that NOA are also present. On the other hand, N02 does not accumulate in most of the world s ocean, specifically in the deep ocean where the Crenarchaeota, suspected to be AOA, constitute up to 40% of the microbial cells. If AOA are abundant and active, the resident N02 oxidizing assemblage is clearly capable of keeping up with them. On balance, this argues that most of that 40% of cells is not very active in NH3 oxidation, or another 40% of the assemblage would be required to consume the N02.  

Our understanding of the biochemistry of nitrification is based largely on insights from cultivated strains. Molecular data obtained from clone libraries indicate that the most important AOB in the ocean are not represented in the culture collection. The same is probably true for NOB, but much less molecular information is available for these organisms. At this stage, the most 

Advances in biomedical applications of nanomaterials require a multidisciplinary research orientation with a focus on both the engineering aspects of nanofiber mats as well as their biological interactions at the implant site. W.-J. Li et al. (2005a) suggest two promising directions for future research bioactivation and incorporation of controlled release functionality into polymers. 

A review of the literature suggests materials selection criteria for scaffold design needs to be guided by both the chemical nature of the polymer and the physical characteristics of the nanofiber mat (Dong, W., et al. 2006). The various polymers electrospun into nanofibrous and 

Anderson, K. I., Wang, Y.-L., and Small, J. V. (1996). Coordination of protrusion and translocation of the keratocyte involves rolling of the cell body. T. Cell Biol. 134, 1209-1218. 

Borisy, G. G., and Svitkina, T. M. (2000). Actin machinery Pushing the envelope. Curr. Opin. Cell Biol. 12, 104-112. 

Bullock, T. L., McCoy, A. J., Kent, H. M., Roberts, T. M., and Stewart, M. (1998). Structural basis for amoeboid motility in nematode sperm. Nature Struct. Biol. 5, 184-189. 

Buttery, S. M., Ekman, G. C., Seavy, M., Italiano, J. E., Stewart, M., and Roberts, T. M. (2003). Dissection of the Ascaris sperm motility machinery identifies novel proteins involved in MSP-based amoeboid locomotion. Mol. Biol. Cell 14, 5082-5088. 

Research on Fe-S proteins in the Johnson laboratory is supported by grants from the National Institutes of Health (GM45597 and GM51962) and by a National Science Foundation Research Training Grant Award to the Center for Metalloenzyme Studies (BIR-9413236). 

Johnson, M. K. In Encyclopedia of Inorganic Chemistry King, R. B., Ed. John Wiley Sons Chichester, 1994 pp. 1896-1915. 

In Iron-Sulfur Proteins Spiro, T. G., Ed. Wiley-Interscience New York, 1982 pp. 1-66. 

Battistuzzi, G. Borsari, M. Ferretti, S. Luchinat, C. Sola, M. Arch. Biochem. Biophys. 1995, 320, 149. 

Nakazawa, K. Hon-NEuni, K. Oshima, T. Biochim. Biophys. Acta 1981, 668, 277. 

DNA-binding mechanism that does not involve DNA damage or disruption of chromosomal integrity [86]. 

We are grateful to the National Institutes of Health for research support E.J. F. is supported by an NIH Research Service Award and a Ralph M. Parsons Fellowship. B. S. E. is supported by a pre-doctoral fellowship from the Howard Hughes Medical Institute. 

Arcamone, F., S. Penco, P. Orezzi, V. Nicolella, and A. Pirelli. Structure and synthesis of distamycin A. Nature 1964, 203, 1064-1065. 

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SCHUHMANN, E., I. HaUPT, H. ThRUM, U. Taubeneck, and U. May. Effect of distamycin A and netropsin on normal cells and wall-less cells of Escherichia coli W 1655 F+. Zeitschrififot Allg. Mikrobiologie 1974, 14, 321-327. 

As each BVMO is limited in substrate specificity, it is crucial to have a large collection of these oxidative biocatalysts available. Except for expanding the scope of possible reactions, a large toolbox of BVMOs would also increase the chance of being able to perform any wanted specific chemo-, regio- and/or enantioselective reaction. This contrasts with the present situation as only a relatively small number of BVMOs can be exploited for biocatalytic purposes. Therefore, it is still crucial to discover or engineer BVMOs with novel biocatalytic properties. 

The recently developed methodology for enzyme discovery that is based on random DNA isolation and subsequent screening (metagenome mining) is 

Except for extending the toolbox of type 1 BVMOs, it can also be worthwhile to explore other types of Baeyer-Villiger catalysts. As mentioned above, type 11 BVMOs have hardly been explored and new types of BVMOs have been discovered in recent years. Eurthermore, Baeyer-Villiger oxidation activity has also been introduced into enzymes that normally catalyze other (hydrolytic) reactions. This 

Bennett, A. J. Undergr. Res. 2004, 6 (http //www.clas.ufl.edu/jur/200409/papers/paper bennett. html). 

MRI has been used as a non-invasive quantitative visualization technique to investigate a class of complex Taylor-Couette-Poiseuille (TCP) flows, which constitute a prototype of many mixing or fractionation processes. Here we focused on the vicinity of the Stationary Helical Vortex (SHV) regime characterized by a 

This chapter is dedicated to P. C. Lauterbur who continues to inspire us. 

3 Perry s Chemical Engineering Handbook, McGraw-Hill, New York, 1999. 

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Holland, R. D. Wilkes, J. G. Rafii, F. Sutherland, J. B. Persons, C. C. Voorhees, K. J. Lay, J. O., Jr. Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Comm. Mass Spectrom. 1996,10,1227-1232. 

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The use of X rays is providing a rare glimpse of the in situ structure of electrochemical interfaces, and as these experiments become more widespread, a wide range of phenomena will be explored. I am certain that these studies will provide the basis for a better understanding and control of electrochemical reactivity. 

Our work was generously supported by the Materials Science Center at Cornell University, the National Science Foundation, the Office of Naval Research, the Army Research Office, and the Dow Chemical Company. Special thanks to Dr. Michael J. Bedzyk (CHESS) and to Dr. James H. White as well as to Michael Albarelli, Mark Bommarito, Dr. Martin McMillan, and David Acevedo. The work on the copper and silver underpotentially deposited on gold 

Sparnaay, The Electrical Double Layer, in The International Encyclopedia of Physical Chemistry and Chemical Physics, Vol. 14, Pergamon Press, Glasgow, 1972. 

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New developments in pharmacogenomics will impact on drug design at three main levels 

If we are ever to achieve personalized drug therapies, the above issues will have to be addressed. 

Absorption, in general, is treated as a physicochemical transport process based on computations of logP (the octanol/water partition coefficient) and solubility governed by factors such as polar surface area on the molecule. It is conceivable that SNPs in drug transporter genes will affect the pharmacokinetic properties of compounds and, therefore, these may have to be taken into consideration in the design process. 

Genomic pre-screening of patients for SNP mutations in drug metabolism will improve the utility of clinical trials by focusing attention on the response of specific subpopulations to drug treatment. The consequence of this approach is that it should be possible to industrialize the creation of individual therapies, although at a significant increase in cost. 

1 Drews JJ. Drug discovery A historical perspective. Science 2000 287 1960-1964. 

The scope for further developments in the chemistry of seven-membered heterocyclic systems is considerable, particularly with respect to multi-heteroatom component systems. New synthetic methods are needed for these systems and ring-fused derivatives. The demand for such systems is likely to be largely driven by the search for structurally novel drug leads. 

Nomura, M. Shibata, R. Katsuragi-Ogino, M. Koyama, M. Nakajima, T. Inoue, T. Ohno, T. Tatsuoka, Bioorg. Med. Chem. 2006,14, 1978. 

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Chumakov, Y.A. Simonov, G. Bocelli, M. Gdaniec, S.V. Vlassiuk, V.I. Pavlovsky, Chem. Heterocycl. Compd. (Engl. Transl.) 2006,42,907. 

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Edited by Peter H. Seeberger Copyright 2001 John Wiley Sons, Inc. ISBNs 0-471-37828-3 (Hardback) 0-471-22044-2 (Electronic) 

Further, there is an increased reliance on use of in vitro dissolution as a surrogate marker for in vivo blood level data. When dissolution is used as a QC test for IR products, it is generally a single-point dissolution test and is represented 

Guidance for Industry Dissolution Testing of Immediate Release Solid Oral Dosage Form. Aug. 1997. 

Guidance for Industry Extended Release Solid Oral Dosage Forms Development, Evaluation and Application of In Vitro/ In Vivo Correlations. Sep. 1997. 

Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. Aug. 2000. 

Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations. Oct. 2000. 

Special thanks to all the PhD and Diploma Students Involved in this project (Anne Regelin, Heike Wursthorn, Caria Kusters. Stefan Fankhaenel, Thomas Fichert). 

Wadhwa PD, Zielske SP, Roth JC, Balias CB, Bowman JE, Gerson SL. Cancer gene therapy scientific basis. Annu Rev Med 2002 53 437-452. 

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Porteous DJ, Dorin JR, McLachlan G, et al. Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther 1997 4(3) 210-218. 

Friedmann T, Roblin R. Gene therapy for human genetic disease. Science 1972 175(25) 949-955. 

While the methods described in this chapter have been optimized for affinity selection-MS using continuous SEC, they are readily adaptable to spin-column, gel permeation, or other well validated and highly accessible two-stage AS-MS designs. The use of AS-MS for studying protein-ligand interactions, especially for the discovery of ligands from pools of compounds, has been reported by a number of experts in the pharmaceutical industry and academia over the past decade. 

Due to the advantages offered by AS-MS, it can be anticipated that these techniques will be increasingly applied by medicinal and synthetic organic chemists, biochemists, analytical chemistry experts and other researchers throughout the pharmaceutical discovery community. 

Euture improvements of the methods presented here will include modifications that enable determination of the thermodynamic parameters of protein-ligand binding interactions. Eor example, ALIS-based Kd or off-rate measurements at varying temperatures could yield useful relationships between chemical structures and binding thermodynamics. Ready access to such information, especially for targets that otherwise require complex bioassays for their study, could posi- 

The authors gratefully acknowledge Satish Jindal, Jerry Shipps, Arshad Siddiqui, and Charles Whitehurst for valuable discussions and critical reading of the manuscript, Ciamac Moallemi, Kieth Mason, and Vladimir Bozin for lending their mathematical expertise, and Yongmin Hou for experimental assistance. 

1 Falb, D., Jindal, S. Chemical genomics bridging the gap between the proteome and therapeutics. Curr. Opin. Drug Discovery Dev. 2002, 5, 532-539. 

A key issue will be the integration and federation of various data sources that are already available. One can imagine a data environment where all data from toxicoge-nomics to every biochemical assay around a compound is streamlined and easily accessible for every researcher. Having this kind of global molecule profile will also make it possible to describe the differences between compounds in detail and finally lead to novel ideas on how to improve lead compounds to ultimately make better drugs. 

1 Adams, C.P. and Brantner, V.V. (2006) Estimating the cost of new drug development is it really 802 million Health Affairs, 25 (2), 420-428. 

2 DiMasi, J.A., Hansen, R.W. and Grabowski, H.G. (2003) The price of innovation new estimates of drug development costs. Journal of Health Economics, 22 (2), 151-185. 

4 Hamon, J., Azzaoui, K., Whitebread, S., Urban, L. and Faller, B. (2006) In vitro safety pharmacology profiling. European Pharmaceutical Review, 1, 60-63. 

Before a vaccine is given to the general population, all potential adverse events cannot be anticipated. Thus, many vaccines undergo phase IV studies—formal studies on a vaccine once it is on the market. Also the government relies on the Vaccine Adverse Event Reporting System to identify problems after marketing begins. Adapted from an FDA document) 

In addition to the classical approaches described above, scientihc and technological advances in recent years have engendered a number of experimental approaches. Some of these are likely to have major impacts on the future direction of vaccine development. 

With better understanding of the precise nature of the antigen-binding epitopes for 

ITABLE 11.3. Novel adjuvant systems and vaccine delivery technologies 

Emulsions SAE (Syntex) ME59 (Chiron) Provax (IDEC) TiterMax (Vaxcel) [65-68] 

The work described in this Chapter illustrates the variety of chemistry exhibited by superoxometal complexes. These compounds couple with free radicals (RC(O)OO, NO, and NO2) almost as fast as the parent superoxide radical, but the lifetimes of the LMOO complexes are by orders of magnitude longer than that of the transient HO2/O2. These features make the LMOO reactions not only easier for the curious to observe, but perhaps also more important in real biological and catalytic systems, where the longer lifetimes should translate into a greater chance for reactions with substrates. 

The radical reactivity of Craq002+ has been especially well documented. This complex is ideal for mechanistic studies, not only because of the convenient combination of lifetime and reactivity, but also because it is nearly inert to visible-light photolysis. Photochemical generation of reactive partners in the presence of Craq002+ is thus possible, and rapid radical reactions can be observed and studied directly, as shown on the examples of acylperoxyl radicals, NO, and NO2. 

Hydrogen abstraction by Craq002+ from C-H, OH, and Rh-H bonds is kinetically facile provided the thermodynamics are favorable (143). Much work remains to be done with other LMOO compounds to sort out various influences on the strength of the LMOO H bonds, and thus, by implication, the tendency of LMOO to abstract hydrogen. 

The cross-coupling with acylperoxyl radicals was shown to lead to high-valent metal species and reactive organic intermediates (144). The Craq002+/CMe3C(0)00 reaction appears to be the sole example of such chemistry reported so far. Extension to other metals and types of radicals is essential before one can even begin to understand whether such reactions take place in catalytic oxidation systems and/or in aerobic organisms, and whether or how to exploit or suppress them. 

Craq002+ also acts as a catalyst for oxidations with O2 in the presence of HNO2. Radical coupling, this time with NO, is again an essential mechanistic step. The catalysis takes advantage of the demonstrated preference for an intermediate, Craq02 +, to react in two-electron, hydride-transfer steps with organic materials. Reactivity studies of potential intermediates in other systems may uncover new catalytic powers of LMOO species. 

In the preceding 5-10 years there has been increasing recognition of the insights into both catalyst and reactor performance offered by MRI methods. The application of 

MRI to characterize hydrodynamics within reactors is already established. The extent to which the potential of MR to study both hydrodynamics and chemical conversion is fully realized will depend on our ability to integrate the well-established MR spectroscopy techniques in liquid- and solid-state NMR into imaging pulse sequences, and still provide quantitative data in the magnetically heterogeneous environments typical of catalysts and reactors. 

The reports from initial clinical trials suggest that the level of immunosuppression achieved by belatacept is equivalent to cyclosporine in renal transplant patients with less chronic allograft nephropathy, stable kidney function and improved cardiovascular and metabolic profiles. 

Ballow M. 1997. Mechanism of action of intravenous serum immunoglobulin in autoimmune and inflammatory diseases. J All Clin Immunol. 100 151-157. 

Boratynska M, Banasik M, Patrzalek D, Klinger M. 2006. Conversion from cyclosporine-based immunosuppression to tacrolimus/mycophenolate mofetil in patients with refractory and ongoing acute renal allograft rejection. Ann Transplant. 11 51-56. 

Borel JF. 2002. History of the discovery of cyclosporin and its early pharmacologic development. Wien Klin Wochenschr. 114/12 433-437. 

Btinkmann V, Pinschewer PD, Feng L, Chen S. 2001. FTY720 Altered lymphocyte traffic results in allograft protection. Transplantation. 72 764-769. 

and Snyder, L.C. (1989). Radiation Effects Defects in Solids 111-112, 77. 

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Johnson, N.M., Herring, C., and Chadi, D.J. (1987c). Proc. 18th International Conference on the Physics of Semiconductors, ed., O. Engstrom. World Scientific, p. 991. 

Finally, it is important to clarify the complex relationship between maternal sleep (sleep deprivation, sleep fragmentation, and sleepiness), maternal mood, 

Mindell J, Jacobson BJ. Sleep disturbances during pregnancy. J Obstet Gynecol Neonatal Nurs 2000 29 590-597. 

Zaffke ME, McEnany G. Parity and sleep patterns during and after pregnancy. Obstet Gynecol 2000 95 14—18. 

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It appears that small groups of kallikreins may represent enzymatic cascade pathways in certain tissues. For example, it is very likely that at least three kallikreins, hK2, hK3, and hKl 1, which are present in seminal plasma at relatively very large concentrations, may coordinately act as a cascade enzymatic pathway, involved in semen liquefaction or other activities. In contrast, another group of kallikreins, including hK5 and hK7 and possibly many others, seem to be involved in skin desquamation. Similar cascade pathways may be operating in the breast, testis and other tissues. 

Fourth, the demonstration that many of these enzymes have prognostic value in cancer may qualify them as novel therapeutic targets. For example, similar to many other proteases, these enzymes may participate in the digestion of extracellular matrix, thus facilitating tumor invasion and metastasis. The identification of highly specific inhibitors may reveal new therapeutic opportunities. 

certain kallikreins, such as human kallikrein 6, are highly expressed in the central nervous system. It has previously been shown that hK6, and possibly some other kallikreins, are implicated in inflammatory reactions within the central nervous system that lead to demyelination. The association of hK6 and some other kallikreins with AD and multiple sclerosis points to the possibility that some of these enzymes may play important roles within the central nervous system. In addition, many of these enzymes have been found in endocrine tissues such as the islets of Langerhans, thyroid, pituitary, and others, pointing to the possibility that they may participate in prohormone or hormone processing. 

Research on kallikreins in Dr. Diamandis s laboratory has been funded in part by grants from the U.S. National Cancer Institute, the Early Detection Research Network, the Canadian Institutes of Health Research, the National Cancer Institute of Canada, the Natural Sciences and Engineering Research Council of Canada, and IBEX Technologies Inc., Montreal, Canada. 

CHOLESTEROL AND LIPIDS IN DEPRESSION STRESS, HYPOTHALAMO-PITUITARY-ADRENOCORTICAL AXIS, AND INFLAMMATION/IMMUNITY 

Developing processes VOC/air Air pollution control applications Several applications being developed. Significant growth expected as the process becomes accepted 

Light hydrocarbons from nitrogen or hydrogen Reactor purge gas, petrochemical process streams, refinery waste gas Application is expanding rapidly 

Carbon dioxide/methane Carbon dioxide from natural gas Many plants installed but better membranes are required to change market economics significantly 

To-be-developed processes C3+ hydrocarbons/methane NGL recovery from natural gas Field trials and demonstration system tests under way. Potential market is large 

Hydrogen sulfide, water/methane Natural gas treatment Niche applications, difficult for membranes to compete with existing technology 

ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY 

Afione, S. A., Conrad, C. K., Kearns, W. G., Chunduru, S., Adams, R., Reynolds, T. C., Guggino, W. B., Cutting, G. R., Carter, B. J. and Flotte, T. R. (1996). In vivo model of adeno-associated virus vector persistence and rescue. J. Virol. 70, 3235-3241. 

Aitken, M. L., Moss, R. B., Waltz, D. A., Dovey, M. E., Tonelli, M. R., McNamara, S. C., Gibson, R. L., Ramsey, B. W., Carter, B. J. and Reynolds, T. C. (2001). A phase I study of aerosolized administration of tgAAVCF to cystic fibrosis subjects with mild lung disease. Hum. Gene Ther. 12, 1907-1916. 

Albelda, S. M., Wiewrodt, R. and Sterman, D. H. (2002). Gene therapy for lung neoplasms. Clin. Chest Med. 23, 265-277. 

Bartlett, J. S., Kleinschmidt, J., Boucher, R. C. and Samulski, R. J. (1999). Targeted adeno-associated virus vector transduction of nonpermissive cells mediated by a bispecific F(ab gamma)2 antibody. Nat. Biotechnol. 77, 181-186. 

Clinical application of bioinformatics information is expected to increase dramatically with microarrays expected to play a large role. Better efforts 

In the five statin megatrials, the greatest percent reduction in coronary mortality was recorded in 4S. In this study, even though the risk of CHD death was reduced by 42% in the simvastatin group, 111 patients in this group (5%) still died of their disease in the 5.4 years of the study. Therefore, while the results of 4S and the other megatrials are certainly impressive, much more needs to be done. 

In 4S there was no evidence of any threshold below which further reduction of LDL cholesterol was futile (Pedersen et al., 1998a). 

Although atherosclerosis exerts its most important effects on the coronary vessels, other vascular beds are frequently affected, such as the carotid arteries, the aorta, and the vessels of the legs. However, the possibility that effective lipid lowering could have beneficial effects on atherosclerotic diseases other than CHD has received relatively little attention. Although there is some evidence that hypercholesterolemia is a risk factor for stroke, especially in younger patients (Prospective Studies Collaboration, 1995), the epidemiologic data are not nearly as extensive or unequivocal as for CHD. The first evidence that HMG-CoA reductase inhibitors could reduce the risk of cerebrovascular effects was provided by 4S, in which there was a significant 28% reduction in the 

These elfects on cerebrovascular events and on intermittent claudication suggest that simvastatin and other elfective lipid-lowering treatments may have a general antiatherosclerotic elfect not limited to the coronary bed. Definitive evidence on the elfects of statin therapy in stroke prevention and peripheral vessel disease is likely to be provided by the Heart Protection Study (MRC/BHF Heart Protection Study Collaborative Group, 1999). As noted above, this UK study has randomized over 20,000 patients aged up to 80 to simvastatin 40 mg or placebo, and the 5-year treatment period is scheduled for completion in 2001. Among these patients are 3288 patients with a history of cerebrovascular disease. Because of its size and the broad array of patient types randomized, this study should also provide reliable evidence of the elfect of simvastatin on coronary morbidity and mortality in women, elderly patients, patients with low levels of LDL and HDL cholesterol, patients with peripheral vascular disease, and diabetic patients with or without coronary disease (MRC/BHF Heart Protection Study Collaborative Group, 1999). 

Broijersen, A., Eriksson, M., Leijd, B., Angelin, B., and Hjemdahl, P. (1997). Arterioscler. Thromb. Vase. Biol. 17, 273-278. 

There is significant interest in the formation of chiral conducting polymers, such as chiral poly (aniline), as a result of their potential applications in chiral sensors, 

One family of ionic liquids that has to date only been sparsely investigated for use with conducting polymers is the protic ionic liquids, where the cation has one or more mobile hydrogen atoms. A recent manuscript by Bi ak detailed the synthesis of 2-hydroxy ethylammonium formate [109], which melts at — 82 °C and has a room-temperature ionic conductivity of 3.3 mS cm-1, and reported the ability of this protic ionic liquid to dissolve poly(aniline) (17gmL ) and poly(pyrrole) (no concentration specified). The dissolution of conducting polymers into any solvent is of significant interest for a variety of reasons, such as improving their processability and ease of incorporation into different devices. 

Li et al. [93] have used l-ethylimidazolium trifluoroacetate, which is a Bronsted acidic ionic liquid, as a medium for the electropolymerization of aniline. They report that in this ionic liquid the oxidation potential of aniline is lower (0.58 V compared to 0.83 V in 0.5 M H2SO4) and that the growth rate of the polymer is increased. Further, the resultant films are smooth, strongly adhered to the Pt working electrode and are very electrochemically stable. Similar results have been reported by Liu et al. [92], who found that this was the best ionic liquid for the polymerization of aniline, compared to the unsatisfactory results observed in other protic ionic liquids 1-butylimidazolium tetrafluoroborate, 1-butylimidazolium nitrate and 1-butylimidazolium p-toluenesulfonate, as well as the l-butyl-3-methylimidazolium hydrogen sulfate and l-butyl-3-methyimidazolium dihydrogen phosphate. 

The potential improvements that ionic liquids may impart to conducting polymers have been widely discussed - increased doping levels, smoother films, increased conductivity, decreased over-oxidation and improved electrochemical stability and so on. However, the research to date in this area has only just begun to investigate these hypotheses and demonstrate any material advantages in the use of ionic liquids future directions in this area must focus on some of these issues in addition to simply demonstrating the use of new ionic liquids for conducting polymer synthesis. 

It would also be interesting to measure the degree of solvent swelling of the polymer films in ionic liquids compared to molecular solvents, as this will impact significantly on the ion mobility and thus the electrochemical activity of the polymer. It is expected that this will be lower in ionic liquids compared to molecular solvents - although the extent of this difference may also depend on the thickness of the film - but this is yet to be quantified. 

ASP atomic solvation parameters, BD Brownian dynamics, DEE dead end elimination, DOF 

4285 (1999). Assigning Protein Functions by Comparative Genome Analysis Protein Phylogenetic Profiles. 

751 (1999). Detecting Protein Function and Protein-Protein Interactions from Genome Sequences. 

Huynen, W. L. B. Snel,andP. Bork, Curr. Opin. Struct. Biol., 10,366 (2000). Exploitation 

Narayan, M. Srinivasan, P. Pochart, A. Qureshi-Emili, Y. Li, B. Godwin, D. Conover, T. Kalbfleisch, G. Vijayadamodar, M. Yang, M. Johnston, S. Fields, and J. M. Rothberg, Nature (London), 403, 623 (2000). Comprehensive Analysis of Protein-Protein Interactions 

Monolayer Properties Probed by Surface Forces Measurements 

The interferometric surface forces apparatus (SFA) has played a major role in the discovery and experimental investigation of a variety of surface forces since the early seventies. It has now served its scientific purpose in surface chemistry for more than 30 years. The SFA was envisaged by Tabor and Winterton [1] and later developed by Tabor and Israelachvili [2] and Israelachvili and Adams, and Klein [3-5]. Considerable development of the basic technique has occurred since then, and this has opened new perspectives in studying matter in confinement. 

This chapter aims at reviewing the main development milestones of the SFA and look back at some of the most important experimental achievements in studying monolayers at interfaces with the SFA. It is structured as follows. In Section 2 the function of the basic SFA is described. This has been excellently done by several authors before [6-9] however, we feel that it is a necessary part of the review since it helps to appreciate the development of the SFA that is reviewed in Section 3. Further sections are devoted to an overview of experimental achievements obtained using the SFA. A particular emphasis is put on monolayer studies of surfactants and lipids (Chapter 4) where intriguing behaviour of hydrophobic monolayers and forces between hydrophilic monolayes, including specific interactions, are discussed. In Chapter 5 forces generated by 

Corresponding author. E-mail andra.dedinaite surfchem.kth.se 

As mentioned in Section 9, the highest conversion efficiency observed to date for an amorphous silicon solar cell is 10.1 % (Catalano et al, 1982). The theoretical limit for the conversion efficiency of a single-junction a-Si H cell can be estimated to be —20%. This follows from an upper limit of — 22 mA cm-2 for JK as determined from optical absorption data (optical path length — 2 fim), and from upper limits of —1.0-1.05 V for and -0.86 for the fill factor (Tiedje, 1982). 

As shown in Fig. 19, the conversion efficiency of a-Si H solar cells has improved dramatically in recent years, and we project that efficiencies of — 12-14% will be obtained in the next few years for single-junction cells. Most of the future improvement will probably come from the development of better alloys for doped layers. 

Conversion efficiencies as high as 20% might be achieved by the end of the decade if good-quality intrinsic alloys can be developed for stacked junction cells (see Section 8). Wu and Williams (1983) have estimated a theoretical limit of 38% for a structure employing two stacked junctions, but their calculations did not include the effect of tail states. Kuwano et al. (1983) have estimated that the maximum practical efficiency is -24% for a structure with three stacked junctions. 

If the projections for production costs (see Fig. 18) and conversion efficiencies (see Fig. 19) are realized, then a-Si H solar cells may dominate a 

Carlson, D. E. (1977b). IEEE Trans. Electron Devices ED-24,449. 

The orbital picture is at the core of quantum-chemical thinking /122/ and a rigorous probe of this picture is clearly desirable. Though an orbital picture of resonance formation has persisted for long /18,19/, in the absence of a simple and unequivocal mechanism to identify the resonant orbital, its portrayal 

All in all, the bi-orthogonal dilated electron propagator offers a simple extension of the real electron propagator technique and with the incorporation of higher order decouplings like the E3, E ADC(3) etc. and suitably large and flexible basis sets should offer same power and effectiveness in the treatment of metastable anions and cations as done by its real counterpart for stable bound systems. 

MKM s work in this area has been sponsored by the Department of Science and Technology, India, through their grant no. SP/S1/F60/88. Their support is gratefully acknowledged. MNM is grateful to the CSIR, India for a predoctoral fellowship (no. 9/87(160)/93 EMR-I). 

Linderberg, J., and Ohrn, Y. (1973). In Propagators in Quantum Chemistry (D. P. Craig and R. McWeeny eds.), Academic Press, New York. 

Jorgensen, P., and Simons, J. (1981). In Second Quantization Based Methods in Quantum Chemistry Academic Press, New York. 

There will be an expansion of the domestic market as the supermarkets start to seriously trade in organic product and a critical mass of organic processors gain a foothold. Longer term contracts will assist in providing opportunities for larger conversions to take place. Investors looking for export opportunities will be keen to see an expansion of the domestic market to enable them to maintain a fallback position should the export market fail for their product. 

Since the earliest structures were published based on NMR data, the nature of the computational problem has actually changed. In the mid-1980s, it would be an experimental achievement to have around 10z distance restraints. More recently, structures have been published based on literally an order of magnitude more information.115 To some extent, this trend will continue as instrumentation improves, multidimensional NMR pulse techniques develop,4 116 isotopic labeling becomes more common, and the processing of raw NMR data manages to extract more information.117 

Ideally, this would mean that the process of modeling based on NMR data could become completely automatic and issues such as sampling of conformational space would become less important as structural definition improves. In practice, what will also happen is that data will accumulate so that prior models become less adequate. Thus, for example, one can expect to see more examples where direct NOE refinement makes the isolated spin 

From the point of view of modeling data, there are still some areas that are not well treated, especially systems where dynamics are important. Rather than concentrating on ever larger molecules, it is interesting to note that small noncyclic peptides are generally considered too flexible to be modeled well. 

Several molecular complexes have been studied by NMR,118-121 and aside from their biological importance, these may well turn up new challenges for the interpretation of experimental data. 

Finally, NMR-based structures will, in the foreseeable future, suffer from a poor ratio of data to degrees of freedom, when compared with X-ray crystallographic structures. This suggests that modeling based on NMR data will continue to rely on the quality of the force field used in refinements. Consequently, improvements in force fields will contribute to the quality of NMR structures as will the standard inclusion of solvents in refinement calculations. 

Takahashi, Y. Konno, N. Watanabe, H. Miyashita, M. Sasaki, H. Natsugari, T. Kan, T. Fukuyama, T. Tomita, T. Iwatsubo, ACS Chem. Biol. 2007, 2,408. 

Sivapriya, S. Harihararaputran, V.L.Suhas, N. Chandra, S. Chandrasekaran, Bioorg. Med. Chem. 2007, 15, 5659. 

Manoj Swarna, B.J. Undemb, V.L. Korlipara, Bioorg. Med. Chem. Lett. 2007,17, 890. 

Katayama, M. Fujio, H. Sakashita, K. Inaba, K. Asanob, T. Akira, Bioorg. Med. 

Mishra, P. Garg, P. Dohare, A. Kumar, M.I. Siddiqi, M. Rayb, G. Panda, Bioorg. Med. 

I would like to thank Dr. Scott Walsh for providing data prior to publication. 

Argetsinger, L., Campbell, G., Yang, X., Witthuhn, B., Silvennoinen, O., Ihle, J., and Carter-Su, C. (1993). Identification of JAK2 as a growth hormone receptor-associated tyrosine kinase. Cell 74, 237-244. 

Atwell, S., Ultsch, M. H., De Vos, A. M., and Wells, J. A. (1997). Structural plasticity in a remodeled protein-protein interface. Science 278, 1125-1128. 

Banner, D. W., D Arcy, A. D., Chene, C., Winkler, F. K., Guha, A., Konigsberg, W. H., Nermerson, Y, and Kirchhofer, D. (1996). The crystal structure of the complex of blood coagulation factor Vila with soluble tissue factor. Nature 380, 41-46. 

(1990). Structural design and molecular evolution of a cytokine receptor superfamily. Proc. Natl. Acad. Sci. USA 87, 6934-6938. 

The hazards posed by urban environmental contaminants are not, of course, the only ones posed to ecological and human health. Climate change, access to health care, the provision and maintenance of sanitary and other infrastructure, and numerous other economic and political factors variously impact on ecological and human health in cities. By some measures, and in some locations, urbanites enjoy better health and well-being than their rural counterparts, a difference thought to be due to socioeconomic factors, and access to health care and other social institutions (Perdue et al., 2003). Pohcies to address urban environmental health may be debated within a benefit-risk framework that considers the multiplicity of economic, social and environmental factors that interact and underhe health and well-being. 

It is safe to predict that there will be major effort in understanding the biological roles of copper-containing amine oxidases and the relationship to flavin-containing amine oxidases. The diversity of amine oxidases in all forms of life and their involvement in key cellular processes in plants and mammals underline the importance of this objective. 

With galactose oxidase, our understanding of the catalytic mechanism is less advanced than for amine oxidases but all the essential foundations for continued advances are in place high resolution X-ray structures of native and mutational variant forms, eomplete with advanced spectroscopic 

Amaral, D., Bernstein, L., Morse, D., and Horecker, B. L., 1963, Galactose oxidase from Poly-porus circinatus. a copper enzyme, J. Biol. Chem. 238 2281n2284. 

Ameyama, M., Hayashi, M., Matsushita, K., Shinagawa, E., and Adachi, O., 1984, Microbial production of pyrroloquinoline quinone, Agric. Biol. Chem. 48 561n565. 

Angelini, R., Manes, F., and Federico, R., 1990, Spatial and functional correlation between diamine-oxidase and peroxidase activities and their dependence upon de-etiolation and wounding in chick pea stems, Planta 182 89n96. 

Increasing numbers of pterin-containing molybdenum and tungsten enzymes are being discovered in bacteria. Many are not yet fully characterized, and it is often not known whether additional prosthetic groups 

Goughian, M. P., ed., Molybdenum and Molybdenum-Containing Enzymes. Perga-mon, Oxford, 1980. 

Newton, W. E., and Otsuka, S., eds., Molybdenum Chemistry of Biological Significance. Plenum, New York, 1980. 

and Gewirth, A. A., Inorg. Chem. (submitted for publication). 

There are many potential pitfalls that lie in the way of researchers on the route from the discovery of a mutation in human DNA that codes for a pharmacologically important protein to the development of a clinically useful pharmacogenetic test. Very few such tests have been developed as yet, but a considerable number seem likely to be found useful over the next decade in guiding the treatment of patients with cancer, asthma, depression, hypertension, and pain. 

When the technical barrier of developing tests with adequate sensitivity, specificity, and reproducibility is overcome, it seems very likely that the practice of medicine will evolve so that individual patients can be treated for their diseases with appropriately individualized doses of medicines, or indeed different medicines directed at specific therapeutic targets, based on their genotype or phenotype. 

Kohn LT, Corrigan JM, Donaldson MS, editors Committee on Quality of Health Care in America. To err is human Building a safer health system. Washington, DC National Academy Press 1999. 

Balian JD, Sukhova N, Harris JW, Hewett J, Pickle L, Goldstein JA, Woosley RL, Flockhart DA. The hydrox-ylation of omeprazole correlates with S-mephenytoin metabolism A population study. Clin Pharmacol Ther 1995 57 662-9. 

Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 polymorphism. Clin Pharmacokinet 2002 41 913-58. 

The determination of the three-dimensional crystal structure of the 22-kDa fragment of apoE in 1991 represented a major milestone in the studies of the structure and function of apoE. With this structure, it is now possible to understand and interpret much of what was known previously about the protein. In addition, identification of the structures of the apoE2 and apoE4 variants provides new insight into how apoE interacts with the LDL receptor and how the preference for different lipoprotein classes might be influenced by structure. These structures represent the beginning of the next level of understanding of how 

Beisiegel, U., Weber, W., and Bengtsson-Olivecrona, G. (1991). Proc. Natl Acad. Scl U.S.A. 88,8342-8346. 

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Lund-Katz, S., Weisgraber, K. H., Mahley, R. W., and Phillips, M. C. (1993).y. Biol. Chem. in press. 

(1990). Cholesterol Metabolism, LDL, and the LDL Receptor. Academic Press, San Diego. 

A large amount of work is still needed to understand fully the fundamental physical properties of these unique systems. The number of reports in this area is growing steadily and, as these materials become more readily available, many exciting findings will no doubt appear. These findings, coupled with a growing body of theoretical data, will 

We acknowledge the Department of Energy and the National Science Foundation for sustained support of this work in photoelectrochemistry that made the preparation of this review possible. 

Material B/l Electrode type s Crystal face Solve supp nt- orting electrolyte Redox couple i//% Reference 

91As 1.51 D AloooGaAso.oi epitaxial CH3CN-O.7M LiC104 

IsTF 8-14 Kline etfl/. (1982) Tenne and Wold (1985) Agarwal and Rao (1989) 

In the past century, there has been a tremendous growth in pharmaceutical analyses and the role the analytical group plays in the development of new products. The baton was passed from techniques such as gravimetry, titrimetry, spectroscopy after extraction, and thin-layer paper chromatography to HPLC, gas chromatography, and various autoanalyzers. Emphasis was on tests such as assay, content and blend uniformity, and determination of impurities and residual solvents. 

Pharmaceutical analysis needs more functionality tests for solid oral dosage forms. After all, we know and have a record of the amount of drug added to the batch. The industry needs to take advantage of the modernization of the techniques described within and routinely apply them to in situ analyses 

The pharmaceutical analysis of finished solid oral dosage forms is presented here from the aspect of what makes the delivery form unique and successful, 

Techniques that apply to in situ analysis of the dosage form, its precursor granulations, or powders are discussed. Applications of solid-state NMR, FTIR microspectroscopy, visual and scanning electron microscopy, Raman spectroscopy, NIR analysis, thermal techniques, mass spectrometry, and imaging techniques are presented. 

A summary of new high-throughput applications of methodologies is also presented. Examples are fiber-optic dissolution technology, flow injection analysis, NIR analysis, and robotics. These techniques provide data with less analyst involvement and allow a more thorough batch quality assessment. 

Buzaid, S.-J. Soong, M.B. Atkins, N. Cascinelli, D.G. Coit, et al.. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma, J. Clin. Oncol., 19, 3635-3648 (2001). 

Recent advances in the chemistry of melanogenesis in mammals, J. Invest. Dermatol., 75, 122-127 (1980). 

Wakamatsu, T. Kageshita, M. Fume, N. Hatta, Y. Kiyohara, J. Nakayama, et al.. Evaluation of 5-S-cysteinyldopa as a marker of melanoma progression 10 years experience. Melanoma Res., 12, 245-253 (2002). 

Detection of occult metastatic melanoma by urine chromatography. Cancer Res., 36, 3317-3323 (1976). 

Lawson, D.W. Nixon, D.R. Murray, V.M. Camp, F.M. Ali, et al.. Melanoma detection by enzyme-radioimmunoassay of L-dopa, dopamine, and 3-O-methyldopamine in urine, Clin. Chem., 27, 108-112 (1981). 

While much is known about the interactions of 8O2 with ceria, especially in regards to the thermodynamic species that are formed, a number of important issues are still unresolved. The incentive of finding sulfur-tolerant materials for 08C in three-way catalysis is very large, since it would lessen the need for increasingly lower sulfur contents in fuels. Finding 08C materials that do not adsorb 8O2, or that release sulfur more readily, would be of great commercial interest. 

To develop strategies for this, fundamental information about the nature of the initial adsorption states for 8O2 and H28 would be very helpful. As discussed above, most characterization work to date has involved the final states, such as the sulfates 

The effect of promoters, such as zirconia, on the surface species are also uncertain. There are indications that the composition of the OSC materials can lead to improved sulfur tolerance [50], It is possible that some combinations of oxides might block sulfate formation or destabilize the sulfate, in the same way that practical OSC materials require the presence of zirconia to maintain reducibility in ceria. Finally, just as the reducibility of ceria is structure sensitive [37], there may be structure sensitivity to adsorption of sulfur compounds as well. 

Clearly, understanding sulfur chemistry on ceria is an interesting subject with important implications. Hopefully, major advances will be forthcoming. 

Ceria Cerium Sulfate Cerium Sulfide Supported-Metal Catalysts Oxygen-Storage Capacity Water-Gas Shift Steam Reforming SO2 H2S. 

In summary, having established an animal MOA and human relevance for this MOA, it is appropriate to address dose-response assessment, human exposure analysis, and risk characterization. Thus, the purpose of the human relevance framework is to establish which chemicals (or chemical mixtures) should be considered for a quantitative risk assessment and which do not require further consideration because they present a minimal risk or no risk to humans. Several thoroughly worked examples are presented in Meek et al. (2003). 

Another level of enhanced effort will be in the area of epidemiology, both traditional and molecular, and human in vitro research in support of the identification of key events in humans and of the human relevance of an animal MoA. The recently published National Research Council (NRC) Report, Toxicity Testing in the 21st Century A Vision and a Strategy (NRC 2007), provides a set of research options for enhancing the use of in vitro test systems with an emphasis on human cells. This 

Marrero, J., Gish, R. G., Sherman, M., London, W. T., Srivastava, S., and Wagner, R D. (2008). The degree of readiness of selected biomarkers for the early detection of hepatocellular carcinoma Notes from a recent workshop. Cancer Biomark 4, 19-33. 

Boobis, A. R., Cohen, S. M., Dellarco, V., McGregor, D., Meek, M. E., Vickers, C., Willcocks, D., and Farland, W. (2006). IPGS framework for analyzing the relevance of a cancer mode of action fa-humans. Crit Rev Toxicol 36, 781-792. 

Cahill, D. R, Kinzler, K. W., Vogelstein, B., and Lengauer, C. (1999). Genetic instability and darwinian selection in tumours. Trends Cell Biol 9, M57-M60. 

Cummons, D. Barone, S. Ayral-Kaloustian, J. Skotnieki, Biorg. Med. Chem. Lett. 2005,15, 1641. 

05CPB589 S. Yoshiaki, A. Hiroaki, T. Nocuaki, M. Akira, K. Nori5mki, T. Akihiro, Chem. Pharm. Bull. 

05EJO2449 R. Pedrosa, C. Andres, A. Gutierrez-Loriente, J. Nieto, Bar. J. Org. Chem. 2005, 2449. 

05H481 T. Ohtani, Y. Kawano, K. Kitano, J. Matsubara, M. Komatsu, M. Uchida, F. Tabusa, Y. 

SECM-based methods provide unique experimental capabilities for imaging and quantifying molecular transport in porous membranes. No other experimental method or technique currently exists that provides a means to visu- 

30 SECM images of electroosmotic transport of hydroquinone (HQ) through a single hair follicle in hairless mouse skin. The middle image corresponds to the diffusional flux of HQ in the absence of an applied current (i p = 0). The top image (iapp = 50 /j,A) corresponds to electroosmotic flow from the receptor solution to 

We gratefully acknowledge the contributions and insights of Dr. J. Bradley Phipps (ALZA Corp) to the development of the SECM methodology for imaging transport across porous membranes. Research on SECM imaging of porous membranes in the authors laboratory has been supported by ALZA Corp and the Office of Naval Research. 

EL Cussler. Diffusion Mass Transfer in Fluid Systems. New York Cambridge University Press (1997). 

RC Engstrom, M Weber, DJ Wunder, R Burgess, S Wenquist. Anal Chem 58 844, 1986. 

The successful treatment of experimental CNV with verteporfin PDT led to a series of randomized clinical trials which demonstrated a visual benefit of verteporfin PDT for patients with subfoveal CNY. However, this benefit is achieved with multiple retreatments and the rate of vision loss is still substantial. A recent report from the Verteporfin in Photodynamic Therapy group showed that 29% of patients who received PDT for occult subfoveal CNY lost six or more lines of vision after two years and 55% of these patients lost three or more lines of vision (38). Similarly, the TAP Extension Study found that 37.5% of patients with predominantly classic CNY who were treated with verteporfin PDT lost three or more lines of vision after two years (39). 

Improved treatment outcomes may also be achieved by enhancing the selectivity of PDT. Increasing the specificity of drug delivery is a key component to advancing 

PDT as a therapeutic modality. Antibody-based targeting is one method currently under investigation. In vitro studies using various tumor cell lines have shown that photosensitizers conjugated to monoclonal antibodies can achieve a higher phototoxic effect at lower doses than with drug or antibody alone (44,45). In vivo work in a mouse rhabomyosarcoma model yielded similar results (46). 

Uber die Wirkung fluoreszierender StoffeaufInfusorien. Z Biol 1900 39 524—546. 

von Tappeiner H, Jesionek A. Therapeutische Versuche mit fluoreszierenden Stoffen. Muench Med Wochenschr 1903 47 2042-2044. 

We have presented an account of our development work on KS DFT computational methodologies. The approach taken does not involve certain undesirable approximations which in earlier implementations were necessary for efficiency reasons, and thus is more directly comparable to conventional ab initio implementations. The KS energy procedure is completely well-defined, and is furthermore treated carefully and consistently when computing energy derivatives no additional approximations are introduced which can lead to complications, for example, in computed structures and vibrational frequencies. 

As discussed earlier, the Coulomb problem, with its asymptotically quadratic cost in system size, is the current KS bottleneck. As no other component of the calculation scales higher than linearly (except the diagonalization phase, which is not currently dominant), clearly in order to be able to treat truly large systems a breakthrough in the scaling of the Coulomb contribution is required. 

If the Coulomb problem were made linear, the frontier of molecular size limitation would be pushed back considerably, at which point the diagonalization step would become the dominant one at the new end of the spectrum of tractable chemical problems. Efficient diagonalization of large matrices is a topic of much active research, as the results are applicable in virtually all areas of computational science. 

It is quite likely that DFT will be able to establish a useful and significant niche in modern computational quantum chemistry, and as expected progress continues to be made in the development of improved functionals and programs there is every chance that the scope of these methods will be increased. The theory is greatly appealing from both the abstract and practical perspectives, and the future of its application to chemistry appears bright. It should be pursued with enthusiasm and given its fair chance. 

Schleyer and J. A. Pople, Ab Initio Molecular Orbital Theory (Wiley, New York, 1986). 

The current research priorities include elucidation of the in vivo function of proteins such as CD and CP that need not involve cross-bridge cycling, and resolving the physiological relevance of the experimental situations in which LC20 phosphorylation does not explain contraction. Another potentially fertile topic is identification of mechanisms that modulate MLCK and MLCP activities and, of equal importance, establishing their in vivo significance. 

We gratefully acknowledge Christine Palazzolo and Amy K. Browne for their aid in the production of this chapter and John S. Walker for his helpful discussions and preparation of several of the figures. Research by the authors was supported by the NIH (POl HL 19242) and the American Heart Association (Virginia Affiliate). 

Takano-Ohmuro, H., Minakawa-Matsuo, N., Suga, O., Karibe, H., Kohama, K., and Uchida, M. K. (1991). Biochem. Biophys. Res. Commun. 176, 122-128. 

Taylor, E. W. (1987). In Regulation and Contraction of Smooth Muscle, Progress in Clinical and Biological Research (M. J. Siegman, A. P. Somlyo, andN. L. Stephens, eds.), pp. 59-66. Alan R. Liss, New York. 

The University of Texas Southwestern Medical Center at Dallas Dallas, Texas 

It is clear that a variety of ligands is capable of being transferred between metal centers. Although much qualitative information exists, few quantitative studies have been carried out. More work needs to be done to determine the relative rates of these bimolecular transfer reactions since current data reveal half-lives ranging from seconds to days, depending on the complex. Basic studies are also needed on type IV nonproductive reactions to determine the scope of such reactions and the rate at which they occur. 

The future of such transfer reactions lies in catalysis. One can envision a metal complex activating a substrate and transferring the activated species to a second metal where it reacts further. Such reactions could, in principle, be catalytic in both metals. Such reactions could increase the number of catalytic reactions in an exponential fashion. 

I wish to acknowledge the helpful comments of A. G. Davies, University College, London the support of The Dow Chemical Company and the specific efforts of A. D. Strickler in preparing the manuscript. 

Lockhart, Redistribution Reactions. Academic Press, New York, 1970. 

Over the last 10 years, great strides have been made in understanding the biology of the PPARa. The synthesis of specific and potent PPARa agonists have made it possible to examine the mechanism of signal transduction of the PPARa. Furthermore, the resolution of the crystal structures 

In conclusion, it is worth recalling the list of properties that one might wish for a theoretical model chemistry to have. It reads as follows  

While the many-body perturbation theory satisfies most of these requirements, the development of a robust formalism for dissociative processes and for arbitrary excited states remains an obstacle to routine applications in these areas. 

PTC in SCF solvents offers a plethora of opportunities. Certainly the technique will be both applicable and us ul for a wide variety of reactions. With opportunities to tune selectivity, enhance transport, and to remove solvents, all in an environmentally benign medium, this emerging area of research has great potential. With the recent surge of interest in developing technologies for a sustainable society, PTC/SCF systems can play an important role in industrial ecology. 

Edited by Philip G. Jessop and Walter Leitner WILEY-VCH Verlag GmbH, 1999 

Limit the small-scale laboratory experiments and encourage large-scale pilot tests in laboratory or in the field 

Limit the single contaminant experiments in model soils spiked in laboratory and promote the tests with actual contaminated soils with aged and multiple contaminants 

Extend the electrochemical technology to other contaminated porous matrices such as industrial wastes in order to achieve their sustainable reuse Promote the analysis of experimental results based on the physicochemical properties of contaminants, geochemistry of soU, reaction kinetics, equilibrium constants, and transport parameters, rather than a phenomenological analysis of contaminant removal 

In summary, the importance of full-scale field demonstration projects cannot be overemphasized. The lessons from these projects are invaluable in identifying the advantages and limitations of this technology and in developing effective and economical adaptive field systems based on site-specific conditions. 

Acar YB, Alshawabkeh AN. (1993). Principles of electrokinetic remediation. Environmental Science and Technology 27(13) 2638-2647. 

Small reservoir opening (usually covered by gold membrane) 

Legler LM, Gloeckler Ries LA, Smith MA, Warren LL, Heineman EF, Kaplan RS, Linet MS. Brain and other central nervous system cancers recent trends in incidence and mortality. J Natl Cancer Inst 1999 91 1382-1390. 

Kornblith PL, Walker M. Chemotherapy for malignant gliomas. J Neurosurg 1988 68 1-17. 

Walker MD, Green SB, Byar DP, Alexander EJ, Batzdorf U, Brooks WH, Hunt WE, MacCarty CS, Mahaley MSJ, Mealey JJ, Owens G, Ransohoff JI, Robertson JT, Shapiro WR, Smith KRJ, Wilson CB, Strike TA. Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. N Engl J Med 1980 303 1323-1329. 

It is envisioned that three key steps lead toward an ultimate in vitro reconstitution of PRR. The first would be the in w tro covalent modification of PGNA by Ub- and SUMO-conjugating complexes and is justified from several perspectives. First, most of the proteins (or derivatives thereof) involved in these modifications have been successfully purified. Notably, many of these proteins retain their functions after expression in prokaryotic systems, in which contaminating elements of ubiquitination and sumoylation reactions do not exist. Second, the components and cofactors required for Ub and SUMO conjugation have been well documented, and 

Another difficulty concerning in vitro reconstitution of PRR is that although some of the regulatory mechanisms have now become clear, our understanding of several other aspects is still in its infancy. In our opinion, the following issues are pertinent to our understanding of how PRR is regulated in eukaryotic cells and need to be addressed. 

Second, as discussed before, Rad5 contains predicted structural motifs indicative of involvement in chromatin remodeling. This unique feature of Rad5 among PRR proteins may explain additional phenotypes of its 

Invasion of sister duplex and DNA synthesis using sister template 

Resolution of structure and continuaition of semi-consarvaitivB DNA synthesis 

Over the years, the pharmaceutical industry has learned to accept that in silico screening methods indeed can be an efficient complement to to the point that they have 

Kubinyi, H. Chance favors the prepared mind. From serendipity to rational drug design. J. Recept. Signal Transduct. Res. 1999,19. 15-39. 

Lahana, R. How many hits from HTS . Drug Discov. Today 1999, 4. 447-448. 

Kubinyi, H. The changing landscape in drug discovery. In Computational Approaches to Structure Based Drug Design (Stroud, R. M., Ed.). Royal Society of Chemistry London, 2007, pp. 24-45. 

Drug discovery a historical perspective. Science 2000, 287, 1960-1964. 

So what does the next decade promise That we will treat smarter, with more specific treatments and vaccines that target cancer cells while leaving healthy cells intact. We will decipher even further how our brains react to diseases and therapies. And we will better understand the mechanisms behind cognitive dysfunction. 

Of course, we won t know in advance who will win the raffle and remain cognitively unscathed, and who will not. But just by addressing the questions, some of the riddle unfolds. We know that many cancer survivors experience cognitive problems that are debilitating. We also know that chemotherapy does not cross the blood-brain barrier in very high concentrations. .. at least when the blood-brain 

A leading hypothesis in the field is that a family of molecules called cytokines maybe responsible. Cytokines are inflammatory molecules that are generally produced by white blood cells or sometimes cancer cells. Our bodies pump out these cytokines in response to injury or infection, and some can freely cross the blood-brain barrier. It may be that chemotherapy agents and/or steroids and other medications bundled with treatment or the cancer cells themselves, are causing this cytokine release that can be toxic to our brain tissue. 

So your viral infection is not necessarily what is causing your symptoms directly. The symptoms reflect how your body is reacting in response to cytokine signals. That is why so many different illnesses have symptoms of fever, nausea, and fatigue in common. They 

Cytokines may very well be the most critical component in that cascade of events that leads to chemo brain. If we find that postchemotherapy impairment is conclusively associated with these molecules, then we can aim to develop drugs that disarm or tie up cytokines before they slip into the brain, or that protect brain tissue from their damaging effects. 

During recent years, there have been considerable technological advances in aerosol therapy and increasingly sophisticated methods of assessing how such aerosols are distributed and deposited throughout the lung. However, in order to 

Marcel Dekker, Inc. 270 Madison Avenue, New York, New York 10016 

For many drugs, the optimum site of action remains unknown, and the dose of many therapeutic agents may be less pertinent than their delivery profile down the tracheobronchial tree. Whereas it is likely that steroid therapy for asthma is best delivered to the larger airways, antibiotics for cystic fibrosis may need to be delivered to the more distal airways and alveoli. However, further improvements in aerosol and nebulizer technologies may be required before antiinflammatory agents can be effectively delivered to the periphery of the lung. 

In conclusion, if the potential of recent technological advances in improved aerosol delivery devices is to be fully realized, it is important that we focus on how to get the aerosol to the right site according to the age, maturity, and disease status of the individual. This can be achieved only if both drug delivery and assessment of effectiveness are based on a firm knowledge of the underlying structure and function of the respiratory system in the individual concerned. 

There have been some recent advances in the fleatment of COPD with improvements in bronchodilator therapy providing a degree of palliative relief however, no available therapies alter the progressive decline in pulmonary function that characterizes this disease. Several inflammatory mediators are likely to be in- 

Springer TA. Traffic signals for lymphocytes recirculation and leukocyte emigration the multistep paradigm. Cell 1994 76 301-314. 

Murphy PM, Baggiolini M, Charo IF, Herbert CA, Horuk R, Matsushima K, Miller H, Oppenheim JJ, Power CA. International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors. Pharmacol Rev 2000 52 145-176. 

Rossi D, Zlotiuk A. The biology of chemokines and their receptors. Annu Rev Immunol 2000 18 217-242. 

Text analysis A sensible starting point for any prediction would be to extrapolate current trends. To this extent, it is reasonable to assume that TTS will become entirely data-driven. I think it is incontestable that the front end, or text-processing component, will become entirely statistical. In recent years the advances in statistical NLP have been enormous, having been fuelled by the use of search engines and the need to translate documents. I think many of these techniques are directly applicable to TTS and will be adopted. 

Relationship with linguistics Going back to the issue of the interaction between the 

This appendix gives a brief guide to the probabihty theory needed at various stages in the book. The following is too brief to be intended as a first exposure to probability, but rather is here to act as a reference. Good introductory books on probability include Bishop [45], [46] and Duda, Hart and Stork [142], 

Les Groupes Des Permutations Et Le Calcul Du Nombre Des Composes Otganiques. 

Cayley and Sylvester to the Mathematical Description of Chemical Structure. 

Russell and P. Norvig, Artificial Intelligence A Modem Approach, Prentice Hall, Upper 

Fowler and P. Hansen, in DIMAC Workshop Report, Rutgers University Press, New 

Brunswick, New Jersey, 2001. The Working Group on Computer-Generated Conjectures from Graph Theoretic and Chemical Databases I. 

Presently, our ability to predict the occurrence of serious ADRs is limited in two senses  

Some ADRs - those that are common and obvious - are relatively easy to measure but most serious ADRs are not. This problem essentially reflects the limitations of the data sources we have 

Once an ADR is recognised and, perhaps even well-understood, our ability to prevent it often remains imperfect for two broad 

In overall terms, difficulties we have in predicting, understanding and measuring ADRs hamper preventive efforts but, even if those limitations could be overcome, the mechanisms to minimise as far as possible serious ADRs would still need to be improved. 

The model represented a long-term vision of how pharmacovigilance could be conducted in the future and was underpinned by the following key concepts  

A number of three-dimensional adiabatic reactor network synthesis problems were described in Chapter 7. A paper by Nicol et al. (1997) looks at extending these principles to include heating and cooling utilities. In effect, heat transfer equipment may be incorporated into the optimal reactor structure on the AR boundary. The results are dependent on a number of ideas developed by Godorr et al.(1994). Aspects of this work also involve finding conditions for optimality in four-dimensional space. Further details may be found in the PhD theses of Love (1995) and Nicol (1998). 

The relation between the AR boundary and the Pontrya-gin s maximum principle (a classic optimization procedure) is described in a paper by McGregor et al. (1999). Readers interested in the calculus of variations and optimal control theory are encouraged to investigate these ideas further. 

Similar comparisons between the AR and the popular maximum mixedness and segregated reactor models of Zwietering (1959) have also been undertaken. Readers interested in understanding how these reactor models may be interpreted geometrically and compared to the AR should consult Glasser et al. (1994). Wen et al. (2002) describe how selectivity may be incorporated and maximized for the Van de Vusse system. This analysis is similar to the worked examples discussed in Chapter 5. 

Significant advances in the field of AR theory await discovery. In the following sections, we discuss a number of current research problems in the field, and highlight potential research avenues. 

Atlas of Chronic Kidney Disease in the United States. (2014) 2013 USRDS annual data report Atlas of chronic kidney disease and end-stage renal disease in the United States. Am. J. Kidney Dis. 63 (Suppl. 1), A1-A7 el-e478. 

Benipal, B. and Lash, L.H. (2013) Modulation of mitochondrial glutathione status and cellular energetics in primary cultures of proximal tubular cells from remnant kidney of uninephrecto-mized rats. Biochem. Pharmacol. 85, 1379-1388. 

Agrawal, A.K., Putt, D.A., Hashim, M., Reddy, A., Brodfuehrer, J., Surendran, N., and Lash, L.H. (2009) Assessment of the renal toxicity of novel anti-inflammatory compounds using cynomolgus monkey and human kidney cells. Toxicology 258, 56-63. 

Cummings, B.S. and Lash, L.H. (2000) Metabolism and toxicity of trichloroethylene and 5 -(l,2-dichlorovinyl)-L-cysteine in freshly isolated human proximal tubular cells. Toxicol. Sci. 53, 458 66. 

Currently, mass spectrometry instrumentation for MALDI ion sources has considerable room for growth. Although the above-described hybrids are highly effective, very few are presently commercially available nonetheless, new hybrids continue to be developed and revised fragmentation techniques are being pursued. 

Within the field, however, the greatest need for improvement is in sample preparation. Currently, several companies can provide sample preparation robots to perform a range of tasks, from the detection and slicing of gel electrophoresis 

Modification strategies that are described in this chapter are quite versatile. A wide range of classes of molecules can be attached on carbon. If in case a molecule is not 

Bernard, M.C., Chausse, A, Cabet-Deliry, E, Chehimi, M.M, Pinson, J., Podvorica, E, and Vautrin-Ul, C. (2003) Chem. Mater, 

Stockhausen, Vi, Ghikme, J., Martin, P, Trippe-AUard, G., Randriamahazaka, 

Pazo-Llorente, R., Bravo-Diaz, C., and Gonzalez-Romero, E. (2004) Eur. J. Org. Chem., 15, 3221-3226. 

Dauphas, S., Corlu, A., Guguen-Guillouzo, C., Ababou-Girard, 

Flexible aerogel cross-linked with shape memory polyurethane 

While there is a trade-off between modulus and elastic recovery in polymer-reinforced aerogels using flexible linking groups, the combination of MTMS and BTMSPA used in the 

Pierre A C, Pajonk G M (2002) Chemistry of aerogels and their applications. Chem Rev 102 4243-4265. 

Fricke J (1998) Aerogels - Highly tenuous solids with fascinating properties. J Non-Ciyst Solids 100 169-173. 

Husing N, Schubert U (1998) Aerogels - Airy materials Chemistry, Structure and Properties. Angew Chem Int Ed 37 22 5. 

Exploring the potential for CMPs is an exciting area that is rapidly developing. This is mainly due to the exceptional ability to incorporate functionality by either pre-synthetic modification of building block monomers or by post-synthetic modification of the network. 

Post-synthetic modification of CMPs opens up a wide range of new functionality that can be incorporated. A strategy recently adopted by Ratvijitvech et al. is to design in functionality specifically for post-synthetic modification. A CMP building block with a pendant amine group was synthesised, which was subsequently used for reaction with anhydrides to produce a series of amide-functionalised networks.  

CMPs are yet to reach the exceptional surface areas and pore volumes of ultra porous materials. However, a similar material, PAF-1, did achieve a surface area of 5600 m g , showing that, given an appropriate synthetic strategy, these ultra high surface areas could potentially be achieved. 

A relatively unexplored area for CMPs is their ability to swell. Woodward et al. recently showed that a MOP HCP material can reversibly swell at high pressure to take up exceptional quantities of CO2 at high pressures. CMPs also have the potential to swell in a similar manner, particularly in solvents and organic molecules such as liquid amines.  

Exploration of the electronic structure properties of CMPs is a particularly new area. Recently Xu et al. have shown that CMPs can be redox active, meaning that they have great potential for energy storage. The incorporation of monomers that alter the emission spectra and band gaps of CMPs has much potential and may lead to their use in applications such as semiconductors and light harvesting. 

For a general discussion on agostic interactions, see Brookhart, M., Green, M.L.H., and Wong, L.L. (1988) Prog. Inorg. Chem., 36, 1-124. 

The discovery and development of well-defined, ruthenium-based olefin metathesis catalysts, in Handbook of Metathesis, 1st edn, vol. 1, Chapter 6 (ed. R.H. Grubbs), Wiley-VCH Verlag GmbH, Weinheim. 

Mestrelab Research The EXSYCALC Software Package and Instructions for Crosspeak Analysis Can Be Obtained, Free of Charge, http //www.mestrelab.com (accessed 21 April 2014). 

Neuhaus, D. and Williamson, M.P. (2000) The Nuclear Overhauser Effect in Structural and Conformational Analysis, 2nd edn, Wiley-VCH Verlag GmbH, New York, pp. 185-187. 

(a) Wenzel, A.G., Chatterjee, A.K., and Grubbs, R.H. (2006) Olefin cross-metathesis, in Comprehensive Organometallic Chemistry III Review of the Literature 1993-2005, vol. 11 (eds 

Shea gratefully acknowledges financial support from the National Science Foundation (Career Award 0133504.), the David and Lucile Packard Foundation, and the A. P. Sloan Research Foundation. M. F. was supported by an NSF graduate research fellowship. 

Chothia, Nature, 357, 543 (1992). One Thousand Families for the Molecular Biologist. 

Haber and C. B. Anfinsen, J. Biol. Chem., lY , 1839 (1962). Side-chain Interactions 

Governing the Pairing of Half-cystine Residues in Ribonuclease. 

Anfinsen, Sciewce, 181, 223 (1973).Principlesthat Govern the Folding of Protein Chains. 

The use of optically active reporter genes has been used successfully in a variety of applications to obtain quantitative information regarding biological processes. 

For the specific use of measuring transcriptional activity, the method provides several unique advantages however, several issues must be treated with great care and simple quantification of light emission may not always provide a true representation of the biological effect studied. First, as luciferase expression is 

Several challenges face the future development of BLI. First, the utility of BLI will be greatly enhanced if the spatial resolution of this method can be improved. Several approaches are currently being developed. Coquez et al. (65) reported an approach to use spectral information of light emission to estimate the depth of the luminescence source. Various investigators are working on 

Although BLI is a powerful imaging modality, it will never provide structural resolution equivalent to other modalities. Hence, the most exciting future developments will probably originate in multimodality imaging approaches where the strength of various imaging modalities can be combined. 

Benaron DA, Contag PR, Contag CH. Imaging brain structure and function, infection and gene expression in the body using light. Philos Trans R Soc Lond B Biol Sci 1997 352(1354) 755-761. 

The past decade has revealed unexpected effects in isotopic compositions, even for heavy metals such as Sr, Hg, Tl, and U [13, 76-78]. More conventional systems were explored through field observations, theoretical studies and experimental results that provided a framework for interpreting natural studies. After techniques had been developed to make measuring these isotope systems routine, emphasis shifted to reveal the processes behind variations in the isotopic compositions. This should be the same path that metal isotope research follows, but as yet it is more of a survey of what variations there are. 

1 Walker, G. (2005) Sociological theory and the natural environment- Hist. 

2 Wasylenki, L.E., Anbar, A.D., Hermann, L.J., Mathur, R., Gordon, G.W., and Brantley, S.L (2007) Isotope fiactionation during microbial metal uptake measured by MC-ICP-MS. 

3 Siebert, C. (2008) Double spiking and the analysis of non-traditional stable isotopes by MC-ICPMS an update. Geochim. Cosmochim. Acta, 72 (12S), A867. 

4 Dobretsov, N.L, Kolchanov, NA., and Suslov, V.V. (2006) On the early stages of the evolution of the geosphere and biosphere. Pcdeontol. f, 40 (4), S407-S424. 

Johnson SR. Lymphangioleiomyomatosis. Eur Respir J 2006 27(5) 1056-1065. Sullivan EJ. Lymphangioleiomyomatosis a review. Qiest 1998 114 1689 1703. McCormack EX. Lymphangioleiomyomatosis a clinical update. Chest 2008 133(2) 507 516. 

Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006 355(13) 1345-1356. 

Franz DN, Brody A, Meyer C, et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med 2001 164(4) 661-668. 

Costello LC, Hartman TE, Ryu JH. High frequency of pulmonary lymphangio-leiomyomatosis in women with tuberous sclerosis complex. Mayo CUn Proc 2000 75(6) 591-594. 

Potential uses for photodegradable polymers, such as E/CO, will exist wherever plastics littering occurs. It has been estimated that almost a billion pounds of plastics find their way into the world s waterways annually [23]. Because E/CO floats and maintains much of its photodegradability when in water, there should be commercial opportunities for E/CO in marine packaging, fishing gear, and similar applications. 

Many food contact applications are expected to be developed if the US Food and Drug Administration sanctions the use of E/CO films for food packaging. 

Solutions to the solid waste disposal problems facing the world will include recycling, incineration, and land fill where feasible. However, in those instances where collection is prohibitive by expense, such as roadside and beach littering, photodegradation will remain a viable solution and E/CO will find additional applications, repeating its success as the material of choice for the degradable carriers for beverage cans. 

Brubaker, M. M. (1950) Interpolymers of carbon monoxide and method of preparing the same, US Pat. 2,495,286 (to DuPont), 24 January. 

and Dorris, M. C. (1987) Photodegradable polyethylene. Proceedings of Symposium on Degradable Plastics, SPI, Washington DC, 10 June, pp. 51-5. 

Another area of research that is of great importance to nanoparticle biosensors are new methods to reproducibly synthesize anisotropic nanostructures. This is an active area of research as seen by new methods for synthesis of anisotropic nanostructures such as nanoprisms, cubes, wires, and belts that have recently appeared in the literature. However, the optimization of these synthetic procedures to control the shape and size dispersity, scale up of the synthesis, and long-term stability of the nanostructures- issues that, to date, have received significantly less attention- will need to be addressed as these nanostructures begin to make the transition from basic science to technology. 

The context of this chapter aims to discuss the most recent advances in the use of injectable biodegradable materials for bone tissue engineering. The current clinical need, design criteria, and material property requirements were illustrated followed by an overview of the latest material, cellular, and drug 

This work was supported in part by an award R21EB009795 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and a National Science Foundation (NSF) CAREER award 0954109. 

Hiles and J. Hodde, Int. Urogynecol. J. Pelvic Floor Dysfunct., 2006, 17 (Suppl 1), S39. 

Biodegradable Injectable Systems for Bone Tissue Engineering 

Schmidmaier, B. Wildemann, T. Gabelein, J. Heeger, F. Kandziora, N. P. Haas and M. Raschke, Acta. Orthop. Scand., 2003, 74, 604. 

Chitosan-nHA nanocomposites have been proven to increase cell proliferation, porosity, increase the osteogenic marker and bone formation. However, the numbers of in vivo studies suggest that addition of a third component in the chitosan-nHA composite is necessary for better bone formation. Proper utilization with 

This research was supported by a grant from Marine Bioprocess Research Center of the Marine Biotechnology Program funded by the Ministry of Oceans and Fisheries, Republic of Korea. 

Rezaei-Tavirani, M., Biazar, E., Heidari, K.S., Jahandideh, R., 2011. Mechanical properties of chitosan-starch composite filled hydroxyapatite micro-and nanopowders. Journal of Nanomaterials 2011 16. 

Zimmermann, E.A., Schaible, E., Tang, S.Y., AlUston, T., Ritchie, R.O., 2011. Characterization of the effects of x-ray irradiation on tbe hierarchical stmcture and mechanical properties of human cortical bone. Biomaterials 32 (34), 8892-8904. 

Bhat Kalambettu, A., Rajangam, R, Dharmalingam, S., 2012. The effect of chlorotrimetbylsi-lane on bonding of nano hydroxyapatite with a chitosan-polyacrylamide matrix. Carbohydrate Research 352, 143-150. 

The catalysts have been explored for metal-air, lithium thionyl chloride, and lithium-sulfur batteries. It is obvious that a significant amount of additional development is necessary to make any one of these batteries commercially viable. 

While composite separators have excellent wettability and thermal stability, they are not suitable for cell assembly. The commercially available Separion separators have been shown to overcome some of the problems associated with manufacturing. The Separion separators essentially consist of a flexible perforated nonwoven polymeric mat with porous ceramic coating on both sides. For 

Korovin, N. (2006) in New Carbon Based Materials for Electrochemical Energy Storage Systems (ed. I.V. Baruskov), Springer, 

Wiesener, K. and Garche, J. (1981) Elec-trochemische Stromquellen, Akademie Verlag, Berlin. 

(1972) Final Report Under Contract DAA307-71-0249 (ECOM), Energy Research Corporation. 

Although PTR-MS provides a broad-based technology for the detection of threat agents, another limitation (other than cost) for its adoption is the provision of a rapid cycle time for detection, that is, the whole process of sampling, analysis and recovery (no memory effects) ideally needs to be complete within tens of seconds. No residues must remain from compounds that readily adsorb on surfaces if PTR-MS is to be adopted for security 

(2009) Triacetone triperoxide detection using low reduced-field proton transfer reaction mass spectrometer. Int. J. Mass Spectrom. 285, 100. 

Harper, R. J., Almirall, J. R., Furton, K. G. (2005) Identification of dominant odor chemicals emanating from explosives for use in developing optimal training aid combinations and mimics for canine detection. Talanta 67, 313. 

Mayhew, C. A., Sulzer, R, Petersson, F. et al. (2010) Applications of proton transfer reaction time-of-flight mass spectrometry for the sensitive and rapid real-time detection of solid high explosives. Int. J. Mass Spectrom. 289, 58. 

In 2004, more than 100 million dialyzers were produced worldwide. The breakdown is approximately as follows  

With the planned consolidation of the top four U.S. dialysis providers into two vertically integrated companies, the field of available dialyzers is likely to narrow. Meanwhile, the decrease in dialyzer reuse will continue to drive increased production. Given that the Center for Medicare and Medicaid Services (CMS), formerly known as the Healthcare Financing Administration (HCFA), will continue its downward pressure on costs, and possibly institute a capitated payment system (i.e., a fixed monthly payment to cover all patient costs including hospitalization), only incremental improvements in commercially available dialyzer membranes are expected in the next 5 years. 

While current therapy is believed to be effective in the clearance of small solutes such as urea, improved removal of middle molecules and protein-bound solutes is desirable. Henderson et al. (2001) point to the importance of quantifying the removal of larger toxic solutes in the fight of increasing evidence that shows a positive correlation between survival and middle molecule clearance in hemodialysis patients. A number of studies are underway to enhance the removal of middle molecules. These studies include (1) variations in modes of dialysis, (2) changes in dialyzer design to improve internal filtration, (3) targeted removal of specific molecules, and (4) increased frequency of dialysis. 

New dialysis machines with on-line generation of sterile replacement fluid hold promise for overcoming these drawbacks. 

Immunoadsorption is another way to remove middle molecules, either specifically or nonspecificaUy. Adsorptive processes can be carried out either by chemically modifying a hemodialysis membrane to create adsorption sites or by the use of an add-on device during hemodialysis. It should be mentioned that the 1 to 2-m membrane surface area on the hollow-fiber lumen is much smaller than the surface area within the porous membrane structure and may be insuBicient to provide significant toxin removal. However, one could argue that adsorptive sites within the membrane wall offer httle benefit unless significant back filtration of a toxin is taking place because it makes no difference to the patient whether a toxin is adsorbed within the membrane walls or flushed away with the spent dialysate. 

The author thanks the National Science Foundation under Grant No. CHE-0449853 and Temple University for financial support. David Yarkony is thanked for introducing the author to the field of conical intersections several results presented here were obtained in collaboration with him. 

Teller, J. Phys. Chem., 41, 109 (1937). The Crossing of Potential Surfaces. 

1 (1974). Physical Basis of Qualitative MO Arguments in 

Potential Energy Surfaces of the Same Symmetry. Systematic Characterization Using a Lagrange Multiplier Constrained Procedure. 

Method for the Location of the Lowest Energy Point on a Potential Snrface Crossing. 

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As on previous occasions, the reader is reminded that no very extensive coverage of the literature is possible in a textbook such as this one and that the emphasis is primarily on principles and their illustration. Several monographs are available for more detailed information (see General References). Useful reviews are on future directions and anunonia synthesis [2], surface analysis [3], surface mechanisms [4], dynamics of surface reactions [5], single-crystal versus actual catalysts [6], oscillatory kinetics [7], fractals [8], surface electrochemistry [9], particle size effects [10], and supported metals [11, 12]. 

R. W. Baker and co-workers. Membrane Separation Systems, Recent Developments and Future Directions, Noyes Data Corp., Park Ridge, N.J., 1991. 

The avaHabihty of photoconductive polymers opens up many areas for research, in addition to electrophotography. These are relatively unexplored areas and represent promising future directions. 

There have been numerous communications on the subject of biodegradation test methods, including aerobic compost (30), anaerobic bioreactor (31), general methodology and future directions (32—34), and a fine review article (24). ASTM (22) and MITI (35) have also set forth standard testing protocols for plastics, as shown in Table 2, whereas OECD test methods (29) are more suited to water-soluble polymers. 

J. M. Juran, M Histo ofManagingfor Quality The Evolution, Trends, and Future Directions of Managing for Quality, ASQC Quahty Press, Milwaukee, Wis., 1995, p. 597. 

W. Adlhoch and K. A. Theis, "The Rheiubraun High Temperature Winkler (HTW) Process," paper presented at the EPRJ Workshop on Synthetic Fuels Status and Future Direction, San Francisco, Calif., 1980. 

Chemical Aspects of Enzyme Technology—Fundamentals, Plenum Press, New York, 1990. Various eds.. Enzyme Engineeiing, vols. 2-5, Plenum Press, New York, 1974—1980. Wingard, L. B., I. V. Berezin, and A. A. Klyosov (eds.). Enzyme Engineeiing—Future Directions, Plenum Press, 1980. 

In this chapter solid-state physics and chemistry future directions in shock-compres-... 

There has for some years been a considerable backlog in the development of practicable prechromatographic methods [5]. It is becoming more and more recognized that the future direction to be taken by trace analysts is to make improvements in the extraction, enrichment and clean-up of the sample and in the optimization of derivatization. It is only in this way that it is possible to employ the sensitive chromatographic techniques optimally for the solution of practically relevant problems. 

Application technique The samples were appUed as bands (ca. 5 mm long) at right angles to the lower edge of the plate (that is parallel to the future direction of development), e.g. with the Linomat III (Camag). 

Decisions affecting the future direction of the organization and its products and services are made from information gleaned through market research. Should this information be grossly inaccurate, over optimistic or pessimistic the result may well be the loss of many customers to the competition. It is therefore vital that objective data is used to make these decisions. The data can be primary data (data collected for the first time during a market research study) or secondary data (previously collected data). However, you need to be cautious with secondary data, as it could be obsolete or have been collected on a different basis than needed for the present study. 

This chapter will first cover the nature of electrophoretic separations, especially those concerning capillary electrophoresis. Comprehensive multidimensional separations will then be defined, specifically in terms of orthogonality and resolution. The history of planar and non-comprehensive electrodriven separations will then be discussed. True comprehensive multidimensional separations involving chromatography and capillary electrophoresis will be described next. Finally, the future directions of these multidimensional techniques will be outlined. 

O.D. Sherby and J. Wadsworth, "Superplasticity-Recent Advances and Future Directions," Prog. Mater. ScL, 33 166 (1989). 

Strand V, Kimberly R, Isaacs JD (2007) Biologic therapies in rheumatology lessons learned, future directions. Nat Rev Drug Discovery 6 75-92... 

Present Status and Future Directions of Plutonium Process Chemistry... 

An overview is given of plutonium process chemistry used at the U. S. Department of Energy Hanford, Los Alamos National Laboratory, Rocky Flats, and Savannah River sites, with particular emphasis on solution chemistry involved in recovery, purification, and waste treatment operations. By extrapolating from the present system of processes, this paper also attempts to chart the future direction of plutonium process development and operation. Areas where a better understanding of basic plutonium chemistry will contribute to development of improved processing are indicated. 

MacKnight, W.J., Baer, E. and Nelson, R.D., eds., "Proceedings of a DOE Workshop Recommending Future Directions in Energy-Related Polymer Research," (1978), Document no. CONF-780643. 

National Research Council, Board on Chemical Sciences and Technology. Future Directions in Advanced Exploratory Research Related to Oil, Gas, Shale, and Tar Sand Resources. Washington, D.C. National Academy Press, 1987. 

The Advanced Seminars have been crucial for evaluating the utility and validity of existing methods and results, discussing potential improvements in methods, and setting priorities for future research. A brief summary of the advances made in previous seminars and future directions of research on chemical and isotopic techniques of diet reconstruction follows. 

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