Summary and Future Direction

Outstanding questions for gene therapy in islet cell transplantation 

Alejandro, R., Lehmann, R., Ricordi, C., Kenyon, N. S., Angelico, M. C., Burke, G., Esquenazi, V., Nery, J., Betancourt, A. E., Kong, S. S., Miller, J. and Mintz, D. H. (1997). Long-term function (6 years) of islet allografts in type 1 diabetes. Diabetes 46, 1983-1989. 

Aniano, K. and Yoon, J. W. (1990). Studies on autoimmunity for initiation of beta-cell destruction. V. Decrease of macrophage-dependent T lymphocytes and natural killer cytotoxicity in silica-treated BB rats.Diabetes 39, 590-596. 

Appels, B., Burkart, V., Kantwerk-Funke, G., Funda, J., Kolb-Bachofen, V. and Kolb, H. (1989). Spontaneous cytotoxicity of macrophages against pancreatic islet cells. J. Immunol. 142, 3803-3808. 

Arreaza, G. A., Cameron, M. J., Jaramillo, A., Gill, B. M., Hardy, D., Laup-land, K. B., Rapoport, M. J., Zucker, P., Chakrabarti, S., Chensue, S. W., Qin, H. Y., Singh, B. and Delovitch, T. L. (1997). Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism. J. Clin. Invest. 100, 2243-2253. 

To date, our understanding of the speciation of metals in hydrothermal fluids and on mineral surfaces has been based largely on the classical Born model. It is clear that we can now go wed beyond this approach and develop an atomistic picture of aqueous solutions based on either quantum mechanics or classical simulations. Classical simulations using simple pair potentials appear to give a reliable picture of of alkali and alkaline earth halide solutions. Some transition metals (such as Zn, Cu and Mn ) can also be treated at this level. Systems where there is hydrolysis and proton transfer, however will require either dissociatable water models or must be done using quantum mechanical calculations. Quantum mechanical calculations are also needed to understand 

The greatest shortcoming of quantum mechanical calculations on metal complexes and mineral surfaces is an inadequate description of solvation. To that end, dielectric continuum models are still of use, but only to describe the long-range solvation effect. With increasing computational power, moreover, the application of plane-wave pseudopotential based ab initio molecular dynamics will allow us to explicitly treat bulk solution effects from first-principles calculations on large systems. 

Improvements of spectroscopic techniques based on synchrotron radiation will allow new probes of hydrothermal solutions and mineral surfaces. However, the interpretation of this data is greatly aided by first-principles calculations of bond lengths and spectroscopic properties. Discrepancies between theory applied to gas-phase molecules and experimental data on aqueous complexes can provide an indirect probe of solvation. The computational technology is sufficiently well developed that there is no excuse for an experimentalist not to employ quantum mechanical and classical simulations to help interpret experimental results. 

The quantitative SNIFTIRS and PM IRRAS were developed three years ago. They allow one to measure the angle between the direction of the transition dipole of an IR band and the normal to the electrode surface. Since the direction of the transition dipole with respect to the coordinates of the adsorbed molecule could be determined with the help of ah initio normal coordinate calculations, these methods ultimately allow one to determine the orientation of molecules adsorbed at the electrode surface. In a short period of time, they have been successfully applied to provide information concerning the orientation of molecules in several organic films. Today, thanks to the availability of these methods, investigations of thin films at the metal/solution interface may be as detailed as they were at the metal/gas or metal/vacuum interfaces in the past 

The authors acknowledge many helpful discussions with Bruno Pettinger, who introduced them to the Fresnel equations calculations. This work was supported by grants from the Natural Sciences and Engineering Research Council of Canada. JL acknowledges the Canadian Foundation of Irmovation for the Canada Research Chair Award. VZ acknowledges the Canadian Foundation for Innovation for the New Opportunities Award. 

Kuramitsu, A. Hatta, W. Sutaka and H. Seki, Surf. Sci. 175 (1986) L787. 

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To date, the overwhelming balance of effort and industrial application in the metabolic engineering field has been based on standard microbial hosts, that is. 

The key aspects ofthe status of thermophilic bacteria relevant to CBP, addressed in detail in the preceding sections, include the following  

Notwithstanding the substantial progress made, there are still important challenges to be overcome in order for thermophUes to be applied commercially for 

Further improvements in the yield and titer produced by C. thermocellum are desirable and likely necessary for many applications. Progress will be fostered by further improvements in genetic tools, both for strains that are genetically tractable as well as strains that are currently intractable. Understanding and development of strains pursuant to robustness under industrial conditions is an important area for future work that is not widely addressed in the literature and has great opportunities for application of genomic science. 

Initial commercial application of thermophilic ethanol production via CBP is most likely and most economically advantageous as a bolt-on to an existing ethanol mill - for example, processing corn, sugar cane, or lignocellulose. Such application would be a significant milestone for thermophiles and use of nonstandard host microbes, and appears to be a possibility in the near future. 

The authors acknowledge the crucial discussion and inputs provided by Prof. A.Q. Contractor during the preparation of this manuscript and the Council of Scientific and Industrial Research India for providing a Junior Research Fellowship to Jasmine Sinha. 

Matsue, M. Nishizawa, T. Sawaguchi, I. Uchida, J. Chem. Soc. Chem. Commun. 1029 (1991) 

Shirodkar, R. Prakash, J. Solid State Electrochem. 4, 234 (2000) 

PEDOT PSS-Based Electrochemical Transistors for Ion-to-Electron Transduction and Sensor Signal Amplification 

Berggren, R. Forchheimer, J. Bobacka, P.-O. Svensson, D. Nilsson, O. Larsson, and A. Ivaska 

The financial support of the National Institutes of Health, Grant HL54826, and the assistance in figure preparation by Dr. Tatjana Kh. Shokhireva and Mary Flores are gratefully acknowledged. 

Walker, F. A. Ribeiro, J. M. C. Montfort, W. R. In Metsd Ions in Biological Systems Vol. 36 Interrelations between Free RadicMs and Metsd Ions in Life Processes Sigel, H. Sigel A., Eds. Marcel Dekker New York, 1999 pp. 619-661. 

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Montfort, W. R. Weichsel, A. Andersen, J. F. Nitrophorins and Related Antihemostatic Lipocahns from Rhodnius prolixus and Other Blood-Sucking Arthropods. Biochim. Biophys. Acta. 2000, in press. 

Although there has been crmsiderable research published on the preparation and applications of aerogels to date there have been relatively few published papers in which the authors focus on the use of aerogels in sensing apphcarirms. From the papers reviewed in this chapter, it is apparent that researchers are taking a variety of approaches to the use of aerogels as platforms for chemical sensors. 

One example of this approach is the recent work by Arachchige and Brock [32], who applied sol-gel chemistry and surface modification to create architectures based on CdSe quantum dots, resulting in highly luminous monoliths. Sensing is an obvious application for these materials. 

Our own work with aerogels as platforms for chemical sensors has been funded by grants from the National Science Foundation (NSF MRI CTS-0216153, NSF RUI CHE-0514527, NSF MRI CMMl-0722842, and NSF RUI CHE-0847901) and the American Chemical Society s Petroleum Research Fund (ACS PRF 39796-BlO). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. 

Dave B C, Duim B, Selverstone Valentine J, Zink J I (1994) Sol-gel encapsulation methods for Biosensors. Anal Chem 66 1120A-1127A. 

Tsionsky M, Rabinovich L, Glezer V, Sampath S, Pankratov I, Gun J (1995) Organically modified sol- 

We have emphasized in this article the development of the density description of atoms and molecules from the theory of its pioneers, Thomas1 and Fermi.  

This simplest, statistical form of the density description already has much to say about the energies of atoms and molecules. But, as we have stressed, it rests on two major assumptions  

Even neglecting (i) and (ii) above, the description s statistical foundations 

The status of Walsh s rules for molecular shapes still needs further fundamental clarification, though their overall usefulness can hardly be in doubt. However, the simplest density description, as shown by March and Plaskett18 for neutral atoms, and by Ruedenberg48 for neutral molecules, does indeed relate the total energy to the sum of orbital energies, with a multiplying factor of 3/2, both for atoms and for molecules at equilibrium. Corrections to this relation undoubtedly involve the chemical potential.50 

As remarked above, considerable progress has resulted from use of the one-body potential of the density description in a one-electron Schrodinger equation approach. In the language of the density description, this is tantamount to treating the single-particle kinetic energy density exactly, as suggested by Kohn 

This contribution summarizes recent progress in the development of synthetic systems for evaluating ligand effects on water activation and catalytic hydrolysis reactions. These combined studies provide strong evidence that systematic examinations of model systems can provide important insight into the chemical details governing reactions of biological metal centers involved in hydrolysis or 

For organometallic systems, acidity values for a number of metal carbonyl aqua complexes have now been reported. In some cases, these complejKS have enhanced rates for water exchange relative to the hexaaqua ion of the same metal. Ease of water exchange in organometallic aqua ions of technetium is essential toward the generation of Tc-labeled biomolecules for radiopharmaceutical imaging applications. 

Lippard, ). M. Berg, Principles of Bio-inorganic Chemistry, University Science Books, Mill Valley, CA, 1994. 

Mancin, P. Scrimin, P. Tecilla, U. To-nellato, Chem Commun 2005, 2540-2548. 

Bertini, C. Luchinat, M. Rosi, A. Sga-mellotti, F. Tarantelli, Inorg Chem 1990, 29, 1460-1463. 

Triazine dendrimers—which are usually cationic in nature—have been largely explored as targets of synthesis and platforms for manipulation. Their application in fields including regenerative medicine will likely derive from the ability of investigators to tune molecular parameters including size, surface chemistry, and ligand density in a controlled and reproducible manner. 

While the commercial application is yet to be realized for this class of materials, scientific challenges remain. Ongoing efforts focus on strategies to accelerate synthesis, including the use of microwave irradiation. Computation is generating hypotheses regarding the design of linkers and the molecular drivers for solubility. Libraries of substantive size—more than 10 000 members—are yet to be realized as well. The role of solid supports in synthesis is also underdeveloped. The results of these efforts will be reported in due course. 

Work presented from the author s laboratory was supported by United States Public Health Service Grants (DK-33793, DK-42921 and AM-01423). The author was also the recipient of a New Investigator Award from the American Heart Association Connecticut Affiliate, Inc. The author is grateful to Peter S. Aronson for his mentorship and critical review of the manuscript. 

Casavola, V., Helmle-Kolb, C. and Murer, H. (1989) Biochem. Biophys. Res. Common. 165, 833-837. 

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Igarashi, P., Cragoe, E.J., Jr. and Aronson, P.S. (1987) Xth ISN Congress Satellite Symposium on Structure, Function and Regulation of Membrane Transport Proteins, Furigen, p. 86. 

These exciting new technologies present challenging new directions for future development. Collectively they represent more of a concept, that of carrying out an experiment using a variable proximity probe to do a user-defined 

These instruments can address both fundamental and applied research problems. Whether one is trying to solve a device development riddle, understand the complicated vapor-phase thin-film growth process, or delve into the fundamental issues of the nature of superconductivity there is a configuration that can suit that problem. Materials science or physics, whatever the issue, structure or property or their relationship to each other, the SPM capabilities, high resolution, and ability to simultaneously measure structure and property make these instruments valuable additions to the electron microscope family. 

Each of the SPMs can make unique or complimentary contributions to the study of high materials. For high-resolution measurements of the LDOS whether at ambient or low temperature, the STM is unsurpassed by its cousin SPMs. The LT-MFM may be better suited to image the vortex lattice and correlate it with microstructure. The STM can directly map the surface variations of the superconducting gap. 

Development of new capabilities is moving more and more in this direction, taking advantage of the power of these techniques to probe local non-averaged structure related properties (spectroscopy) simultaneously with beautiful topographic data. The drive is to show the one-to-one correspondence between structure and property. One such example is a new technique that will map surface capacitive variations that, like the EFM, could be used to evaluate high Tc devices. 

High on that wish list for the future is the design and construction of dual or interchangeable low-temperature AFM/STM probes to study the temperature-and structure-dependent electrical and magnetic properties of high Tc materi- 

This work was supported by the Division of Chemical Sciences, Office of Basic Energy Sciences of the U.S. Department of Energy (DOE) and calculations were performed in part using the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) at the Pacific Northwest National Laboratory. S.M.K. would like to acknowledge helpful discussions with Nels S. Laulainen, Richard C. Easter, and Steven J. Ghan from the Atmospheric Sciences Division at PNNL. The EMSL is funded by the DOE Office of Biological and Environmental Research. Battelle operates Pacific Northwest National Laboratory for DOE. 

Recent research on oceanic diazotrophs has shown remarkable diversity, with numerous species in free-Hving genera Trichodesmium spp., Katagnymene spp., Croco-sphera spp. and Anabaena gerdit) as well as coccoid symbionts with dinoflageUate and 

In benthic environments, ranging from the rhizosphere of shallow water macrophyte communities such as Zostera, Thalassia and Spartim hundreds of different diazotrophic strains have been isolated, and these are typically microaerophyUic or anaerobic, and often are sulfate respiring bacteria. These diazotrophs make significant contributions to the nitrogen economy of their respective plant communities. 

Similarly, in coral reef communities, N2 fixation in carbonate sands are a major source of N2 fixation, and the recent discovery of diazotrophic coccoid cyanobacteria living within the tissues of Montastrea corals suggests that there may well be more diazotrophic symbioses with corals. Many sponges harbor cyanobacteria symbioses, and these may also be important sources of fixed nitrogen. 

There is precious little information on the pathways of fixed N from pelagic diazotrophs to other members of the plankton and nekton. Viral lysis may be a major pathway as is the leakage of fixed N from healthy Trichodesmium cells. Research on of zooplankton in broad areas of the north Adantic suggests that 

Several conundrums remain to be resolved including 1) have we greatly underestimated marine N2 fixation, 2) what are the quantitative contributions of the newly identified diazotrophs, 3) what is the spatial distribution of N2 fixation and 4) to what extent does the nature of nutrient Hmitation control the composition of diazotrophic populations locally and over broader scales. 

Clearly, carbon nanostructures have demonstrated tremendous promise for orthopedic medical apphcations to date, but a number of critical problems need further investigation and sohd solutions before eventual clinical practice. In fact, there are not any commercial orthopedic products based on carbon nanostructures so far. This is probably due to several unsolved problems as described below. 

Toxicity of carbon nanostructures has not been disclosed or understood. While toxicity of fullerenes and CNT are still under debate, relevant studies on new carbon nanomaterials like NCD and graphene have not commenced. Toxicity of materials has a determinative impact on their ultimate application and use, and thus understanding toxicity of carbon nanostructures (both during manufacturing and use) is as imperative as medical application study. 

In conclusion, albumin may be unique among proteins in that so many scientists have spent the largest portion of their professional careers studying very specific aspects of this protein. New appreciation for the complexity and potential applications presented by the structure of albumin promises to consume the careers of many more scientists. 

Nagoaka, S., Kamada, M., and Hiramatsu, K. (1973). Biochim. Biophys. 

Hutchinson, D. W., and Donaldson, D. (1984). Clin. Chim. Acta 136, 197-202. Breckenridge, A., and Rosen, A. (1971). Biochim. Biophys. Acta 229,610-617. 

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The studies presented here illuminate just a few of the exciting possibilities for e use of VSFS to study chemistry at liquid/liquid surfaces. Solvents and adsorbates can be probed and orientations and conformations obtained. Molecular dynamics has recently been employed to gain additional information using the constraints provided by e spectroscopy. The future of this technique lies in expanding the spectrum to longer wavelengths so that more vibrations can be probed in each molecule and more complicated molecules can be studied. The study of interfacial dynamics will also offer exciting opportunities for the future. 

The authors gratefully acknowledge e National Science Foundation (CHE-9725751), the Office of Naval Research, and the Department of Energy, Basic Energy Sciences for funding the studies described from this laboratory. 

Guyot-Sionnest, J.H. Hunt and Y.R. Shen, Phys. Rev. Lett. 59,1597-1600 (1987). 

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To improve the accuracy of implicit-solvent potential energy surfaces, non-electrostatic interactions must be included, although such interactions have received only a brief mention here. The smooth, linear-scaling PCM technology that is discussed here is immediately ready for use in MM/PBSA applications [36, 38], as a replacement for finite-difference electrostatics. Other formulas for the non-electrostatic interactions [47] can also be used in PCM calculations, possibly after some re-parameterization. In general these non-electrostatic interaction formulas depend in some way on the cavity surface area, which is smooth and easily calculable by means of the PCM algorithms discussed herein. 

Particular attention should be paid to the DESMO method [43], as this model appears to be suitable for use with solvents containing dissolved ions that are described by the linearized Poisson-Boltzmann equation. DESMO shows promising accuracy with respect to benchmark LPBE calculations. This includes an anal3 ically solvable model problem consisting of multiple solute cavities, as would be encountered in a study of protein-protein interactions in implicit solvent. 

The authors work on PCMs has been supported by the National Science Foundation (grant nos. CHE-0748448 and CHE-1300603, to J.M.H.], through an Ohio State Presidential Fellowship (to A.W.L.), and through generous allocations of computing time from the Ohio Supercomputer Center (project nos. PAS-0291 and PAA-0003). 

and Silla, E. (1990], GEPOL An improved description of molecular surfaces. I. Building the spherical surface setj. Comput. Chem. 11, pp. 1047-1060. 

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We have developed an automated solid-phase approach for the chemical synthesis of oligosaccharides. Using an acceptor-bound solid-phase 

The advances in automation presented constitute an important first step toward alleviating the difficulty incumbent to carbohydrate synthesis. 

While the path to enhancing automated synthesis is clear, a number of practical challenges remains. Given the recent success of synthetic methods, other bottlenecks have emerged. Notably, the purification of both fully protected and deprotected oligosaccharides is a laborious process. Improvements in currently available techniques are needed to allow for the expedient purification of synthetic material. More efficient methods for the analysis and sequencing of carbohydrates are of major importance. 

Atherton and R. C. Sheppard, Solid-Phase Peptide Synthesis A Practical Approach, 

Angelitti (Ed.), Techniques in Protein Chemistry III, Academic Press, Orlando, 1992, pp. 219-229. 

The results presented here demonstrate that well-defined model catalysts with particle sizes in the 10-100-nm regime can be efficiently processed with lithographic methods. These model catalysts possess most of the desirable characteristics that are required in fundamental heterogeneous catalysis research. There are considerable advantages, compared to model catalysts prepared by, e.g., incipient wetness impregnation methods, which are enumerated  

Control of particle mass and dimensions (size and shape - especially in 

Control over the lateral dimensions of an active support (capture zone, spillover distances). 

Simplifications in the physical and chemical characterization the 2D nature of the nanofabricated model catalysts make them easier to inspect with traditional surface science tools and electron microscopy. 

Simplifications in kinetic modeling with monodisperse particle sizes and separations, and the detailed characterization offered via [4] more systematic studies of the influence of these parameters can be made, and the associated kinetic modeling is then simplified and becomes more accurate. Furthermore, the active catalyst phase is in direct contact with the reacting gas [e.g., no pore diffusion needs to be accounted for, which simplifies mass transport calculations (when needed)]. 

Proceedings of the 31st National Heat Transfer Conference, 1996, 7,157-156. 

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Wegeng, ICt Symposium on Separation Science and Technology for Energy Applications, Gatlinburg, TN, 

1 Potter, C.W. (2001) A history of influenza. Journal of Applied Microbiology, 91, 572-579. 

2 Morens, D.M. and Taubenberger, J.K. (2010) Historical thoughts on influenza viral ecosystems, or behold a pale horse, dead dogs, felling fowl, and sick swine. Influenza and Other Respiratory Viruses, 4, 327-337. 

3 World Health Organization (March 2014) Fact sheet No 211 Influenza (Seasonal), http //www.who.int/ mediacentre/fectsheets/fs211/en/ (accessed 20 February 2015). 

4 Webster, R.G., Bean, W.J., Gorman, O.T., Chambers, T.M., and Kawaoka, Y. (1992) Evolution and ecology of influenza A viruses. Microbiological Reviews, 56, 152-179. 

5 Klenk, H.D. (2012) Influenza virology, in Influenza Virus Sialidase A Drug Discovery Target (ed. M. von Itzstein), Springer, Basel, pp. 1-29. 

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IV. EMERGING PICTURE OF FOOD SYSTEM MOBILITY SUMMARY AND FUTURE DIRECTIONS... 

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