The present volume is a continuation of the EL.B.A. Forum Series, which was initiated in the spring of 1995 with the first volume, entitled From Neural Network and Biomolecular Engineering to Bioelectronics, in which a brief outline of modem bioelectron ics given as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level. " The present volume highlights the aspects of advanced biotechnology and electronics originating from molecular manufacturing, which has been emerging as an independent branch of research. This volume appears in a crucial moment, when significant progress has already been made in this strategic field and when technologies derived from it are recognized as critical for the welfare of our society. In addition, acknowledging to the Italian Ministry of University and Scientific and Technological Research for launching the National Research Program "Technologies for Bioelectronics" in 1992 and for continuation of support of this advanced multidisciplinary research, we would like to acknowledge the support of the National Research Council of Italy through the "Molecular Manufacturing" CNR Strategic Project since 1994. The significant unique role of Technobiochip in the organization of the EL.B.A. Forums and in bringing to light the enormous industrial potential of bioelectronics is duly acknowledged, as well as its attraction and support of top level scientists to the series of EL.B.A. Forums of which this volume is part. Dr. Sergey Vakula of the EL.B.A."

nd During June 13 -June 23 1996, the 2 EL. B. A. Foundation course on Genome, a NATO Advanced Study Institute, was held at Marcian Marina, Isle of Elba, Italy, - sponsored by the North Atlantic Treaty Organization and the EL. B. A. Fundation. The subject of the course was "Genome Structure and Function" with participants selected worldwire from 15 afferent countries. The purpose of the course and of the resulting book is the study of DNA structure (from the primary to the quintemary) and gene expression in the control of cell function and cell cycle progression; the topics were presented by top experts, covering both structural (cbwn to the atomic resolution) and functional (cbwn to gene level) aspects. The topics were presented by top experts and scientists active in the field, with the goal to give an insight into modm problems of genome study and recent ochievements in related fielm of molecular and cell biology, genetic engineering, biochemistry and biophysics, oncology and biotechnology. This resulting book is intenred to give a broad perspecti ve of the current stand of these fields. The major emphasis is towarm a reep unrerstanang of DNA structure and function in intetphase and metaphase chromosomes, originating by the parallel biophysical (namely NMR X-Ray and neutron scattering, spectropolarimetry, image analysis, calorimetry) and biochemical study conwcted on a wire range of cell systems placing the emphasis on either the higher orrer DNA structure or gene structure and function.

The present volume is a continuation ofthe EL.B.A. Forum Series which was initiated in the spring of 1992 in Marciana Marina (Italy), with the first volume entitled From Neural Networks and Biomolecu/ar Engineering to Bioelectronics published by Plenum Press in 1995. Bioelectronics-miginally introduced in April, 1987, at a symposium hosted by CIREF, a research consortium among leading high tech industries in Novara (Italy)---was later defined in two successive consensus reports at the first (Bruxelles, 1991) and second (Frankfurt, 1994) European Union Workshops on this widely interdisciplinary field, as "the use ofbiological materials and biological architectures for information processing and sens- ing systems and devices down to molecular Ievel." lt is worth noting that these workshops gave birth to the first European research program on "lnterfacing Biology with Electronics" during 1996-1999, following the !arge Programma Nazionale Ricerca on "Technologies for Bioelectronics" launched by the ltalian Ministry ofUniversities and Research in 1990. In autumn, 1996, with the second volume, entitledMolecular Manufacturing, the em- phasis was placed on the ernerging parallel area of nanotechnology, independently initiated in Palo Alto, Zurich, Genova, Mainz, and Tokyo by various groups (i.e., IBM, Xerox, Polo Nazionale Bioelettronica, Max Planck Institutes), universities (i.e., Stanford, Genova, Rice, Tokyo), and organizations (i.e., Foresight, Erato, Fondazione EL.B.A., Frontiers Research, MITI) of different sizes, scopes, and latitudes.

This NATO-ASI on BIOPOLYMERS STRUCTURE AND DYNAMICS held between 22nd June 4th July 1986 at Erice (Italy) has brought together scientists from a broad variety of biophysical disciplines - polymer physics, biophysics and physical chemistry, structure and dynamics of polynucleotides, proteins, and polysaccharides - to present the current state of knowledge in their fields, both experimental and theoretical. This Advanced Study Institute was indeed a successfull attempt to enhance the possibility of intersection of a number of research lines that currently are progressing well but are still running largely in parallel with one another: protein folding, single-polymer phase transitions, DNA condensation into liquid crystalline-like arrays, packaging in viruses, and polysaccharide gel formation. Although each phenomenon is distinctive, an awareness of similarities may lead to new ic;leas. The program has emphasized "condensed" forms of biopolymers. We are universally confronted in biology by chain polymers folded on themselves or interlinked in gel-like assemblies, whether we look at the native structure of proteins, the role of polysaccharides in connective tissue, or the genetic apparatus. A number of lectures have been devoted to condensed forms of DNA - closed circular supercoils, toruses, chromatin.

During May 21-June 1 1990, the eleventh course of the International School of Pure and Applied Biostructure, a NATO Advanced Study Institute, was held at the Ettore Majorana Center for Scientific Culture in Erice, Italy, co-sponsored by the Italian Ministry of Universities and of Scientific and Technological Research, the North Atlantic Treaty Organization, the Italian National Research Council, the Sicilian Regional Government and Technobiochip. The subject of the course was "Molecular Basis of Human Cancer" with participants selected worldwide from 15 different countries. The purpose of the course was to address, in a tutorial and structural fashion, the molecular basis of human cancer, including the mechanism of signal transduction in mammalian cells, the genetic mechanism of malignant transformation in man, growth factors, hormone receptors, cell membrane and cytoskeleton, and DNA high order structure. The course had this as its major objective and the resulting book reflects it. The participants were exposed to a critical evaluation of current knowledge about cancer and to some of the key problems that remain as stumbling blocks to our eventual understanding of this important biological and medical problem. Through the media of formal and informal lectures, workshops, symposia and informal discussions, a select group of interested young and senior scientists were acquainted with many of the aspects of human cancer.

This volume represents the fIrst of a series of proceedings of the EL.B.A. Forum on Bioelectronics, a scientifIc discipline at the frontiers of Advanced Electronics and Biotechnology. The name for these forums derives not only from the place (the Isle of Elba in Italy), where the conferences have been held every 6 months since 1991, but also from an acronym: Electronics and Biotechnology Advanced. Bioelectronics is intended as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level" and focuses its attention on three major areas: I New hardware architectures borrowed from the thorough study of brain and sensory systems down to the molecular level, utilizing existing semiconductor inorganic materials (both GaAs and Si) and giga-scale integration; II Protein Engineering, especially of systems involved in electron transfer and molecular recognition, integrated with Metabolism and Chemical Engineering, to develop new biomaterials by learning basic rules of macromolecular folding and self-assembly; m Sensors, thin film and electronic devices utilizing organic compounds and biopolymers, and by implementing nanotechnology bottom up through manufacturing and characterization at the atomic level.

The book addresses the most recent developments in structural and functional proteomics underlying the recent contributions given in these areas by our laboratory to the instrumentations, the methods and the procedures as mutuated from the nanoscale sciences and technologies. These developments introduced in the last few years make now possible protein massive identification (mass spectrometry and biomolecular arrays down to nanoamounts) and protein structural characterization in solution and in crystals down to the atomic scale to an extent and to a degree so far unmatched. Emphasis is placed in the growth by nanobiofilm template of protein crystals of any type and size from millimeter to micron, leading in combination with microfocus synchrotron technology and atomic force microscopy to the definition of a new field called nanocrystallography. The few useful examples being shown, concerning yet structurally unsolved proteins, point this very promising approach nanotechnology-based in structural proteomics using highly focused X-rays. This has not to be confused with the important study of nanocrystals, both organic and inorganic, and novel diamond like nanocomposite materials and devices having 3D protein crystals as matrices to be equilibrated with nanoparticles/gold/silver to be utilized in the most diversified electronic applications here also summarized. vii Acknowledgments We are particularly grateful to Giuseppe Zanotti at the University of Padova for his fundamental collaboration during all the crystallographic studies.

During May 21-June 1 1990, the eleventh course of the International School of Pure and Applied Biostructure, a NATO Advanced Study Institute, was held at the Ettore Majorana Center for Scientific Culture in Erice, Italy, co-sponsored by the Italian Ministry of Universities and of Scientific and Technological Research, the North Atlantic Treaty Organization, the Italian National Research Council, the Sicilian Regional Government and Technobiochip. The subject of the course was "Molecular Basis of Human Cancer" with participants selected worldwide from 15 different countries. The purpose of the course was to address, in a tutorial and structural fashion, the molecular basis of human cancer, including the mechanism of signal transduction in mammalian cells, the genetic mechanism of malignant transformation in man, growth factors, hormone receptors, cell membrane and cytoskeleton, and DNA high order structure. The course had this as its major objective and the resulting book reflects it. The participants were exposed to a critical evaluation of current knowledge about cancer and to some of the key problems that remain as stumbling blocks to our eventual understanding of this important biological and medical problem. Through the media of formal and informal lectures, workshops, symposia and informal discussions, a select group of interested young and senior scientists were acquainted with many of the aspects of human cancer.

The present volume is a continuation of the EL.B.A. Forum Series, which was initiated in the spring of 1995 with the first volume, entitled From Neural Network and Biomolecular Engineering to Bioelectronics, in which a brief outline of modem bioelectron ics given as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level. " The present volume highlights the aspects of advanced biotechnology and electronics originating from molecular manufacturing, which has been emerging as an independent branch of research. This volume appears in a crucial moment, when significant progress has already been made in this strategic field and when technologies derived from it are recognized as critical for the welfare of our society. In addition, acknowledging to the Italian Ministry of University and Scientific and Technological Research for launching the National Research Program "Technologies for Bioelectronics" in 1992 and for continuation of support of this advanced multidisciplinary research, we would like to acknowledge the support of the National Research Council of Italy through the "Molecular Manufacturing" CNR Strategic Project since 1994. The significant unique role of Technobiochip in the organization of the EL.B.A. Forums and in bringing to light the enormous industrial potential of bioelectronics is duly acknowledged, as well as its attraction and support of top level scientists to the series of EL.B.A. Forums of which this volume is part. Dr. Sergey Vakula of the EL.B.A."

The present volume is a continuation ofthe EL.B.A. Forum Series which was initiated in the spring of 1992 in Marciana Marina (Italy), with the first volume entitled From Neural Networks and Biomolecu/ar Engineering to Bioelectronics published by Plenum Press in 1995. Bioelectronics-miginally introduced in April, 1987, at a symposium hosted by CIREF, a research consortium among leading high tech industries in Novara (Italy)---was later defined in two successive consensus reports at the first (Bruxelles, 1991) and second (Frankfurt, 1994) European Union Workshops on this widely interdisciplinary field, as "the use ofbiological materials and biological architectures for information processing and sens- ing systems and devices down to molecular Ievel." lt is worth noting that these workshops gave birth to the first European research program on "lnterfacing Biology with Electronics" during 1996-1999, following the !arge Programma Nazionale Ricerca on "Technologies for Bioelectronics" launched by the ltalian Ministry ofUniversities and Research in 1990. In autumn, 1996, with the second volume, entitledMolecular Manufacturing, the em- phasis was placed on the ernerging parallel area of nanotechnology, independently initiated in Palo Alto, Zurich, Genova, Mainz, and Tokyo by various groups (i.e., IBM, Xerox, Polo Nazionale Bioelettronica, Max Planck Institutes), universities (i.e., Stanford, Genova, Rice, Tokyo), and organizations (i.e., Foresight, Erato, Fondazione EL.B.A., Frontiers Research, MITI) of different sizes, scopes, and latitudes.

This volume represents the fIrst of a series of proceedings of the EL.B.A. Forum on Bioelectronics, a scientifIc discipline at the frontiers of Advanced Electronics and Biotechnology. The name for these forums derives not only from the place (the Isle of Elba in Italy), where the conferences have been held every 6 months since 1991, but also from an acronym: Electronics and Biotechnology Advanced. Bioelectronics is intended as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level" and focuses its attention on three major areas: I New hardware architectures borrowed from the thorough study of brain and sensory systems down to the molecular level, utilizing existing semiconductor inorganic materials (both GaAs and Si) and giga-scale integration; II Protein Engineering, especially of systems involved in electron transfer and molecular recognition, integrated with Metabolism and Chemical Engineering, to develop new biomaterials by learning basic rules of macromolecular folding and self-assembly; m Sensors, thin film and electronic devices utilizing organic compounds and biopolymers, and by implementing nanotechnology bottom up through manufacturing and characterization at the atomic level.

nd During June 13 -June 23 1996, the 2 EL. B. A. Foundation course on Genome, a NATO Advanced Study Institute, was held at Marcian Marina, Isle of Elba, Italy, - sponsored by the North Atlantic Treaty Organization and the EL. B. A. Fundation. The subject of the course was "Genome Structure and Function" with participants selected worldwire from 15 afferent countries. The purpose of the course and of the resulting book is the study of DNA structure (from the primary to the quintemary) and gene expression in the control of cell function and cell cycle progression; the topics were presented by top experts, covering both structural (cbwn to the atomic resolution) and functional (cbwn to gene level) aspects. The topics were presented by top experts and scientists active in the field, with the goal to give an insight into modm problems of genome study and recent ochievements in related fielm of molecular and cell biology, genetic engineering, biochemistry and biophysics, oncology and biotechnology. This resulting book is intenred to give a broad perspecti ve of the current stand of these fields. The major emphasis is towarm a reep unrerstanang of DNA structure and function in intetphase and metaphase chromosomes, originating by the parallel biophysical (namely NMR X-Ray and neutron scattering, spectropolarimetry, image analysis, calorimetry) and biochemical study conwcted on a wire range of cell systems placing the emphasis on either the higher orrer DNA structure or gene structure and function.

The book addresses the most recent developments in structural and functional proteomics underlying the recent contributions given in these areas by our laboratory to the instrumentations, the methods and the procedures as mutuated from the nanoscale sciences and technologies. These developments introduced in the last few years make now possible protein massive identification (mass spectrometry and biomolecular arrays down to nanoamounts) and protein structural characterization in solution and in crystals down to the atomic scale to an extent and to a degree so far unmatched. Emphasis is placed in the growth by nanobiofilm template of protein crystals of any type and size from millimeter to micron, leading in combination with microfocus synchrotron technology and atomic force microscopy to the definition of a new field called nanocrystallography. The few useful examples being shown, concerning yet structurally unsolved proteins, point this very promising approach nanotechnology-based in structural proteomics using highly focused X-rays. This has not to be confused with the important study of nanocrystals, both organic and inorganic, and novel diamond like nanocomposite materials and devices having 3D protein crystals as matrices to be equilibrated with nanoparticles/gold/silver to be utilized in the most diversified electronic applications here also summarized. vii Acknowledgments We are particularly grateful to Giuseppe Zanotti at the University of Padova for his fundamental collaboration during all the crystallographic studies.

This NATO-ASI on BIOPOLYMERS STRUCTURE AND DYNAMICS held between 22nd June 4th July 1986 at Erice (Italy) has brought together scientists from a broad variety of biophysical disciplines - polymer physics, biophysics and physical chemistry, structure and dynamics of polynucleotides, proteins, and polysaccharides - to present the current state of knowledge in their fields, both experimental and theoretical. This Advanced Study Institute was indeed a successfull attempt to enhance the possibility of intersection of a number of research lines that currently are progressing well but are still running largely in parallel with one another: protein folding, single-polymer phase transitions, DNA condensation into liquid crystalline-like arrays, packaging in viruses, and polysaccharide gel formation. Although each phenomenon is distinctive, an awareness of similarities may lead to new ic;leas. The program has emphasized "condensed" forms of biopolymers. We are universally confronted in biology by chain polymers folded on themselves or interlinked in gel-like assemblies, whether we look at the native structure of proteins, the role of polysaccharides in connective tissue, or the genetic apparatus. A number of lectures have been devoted to condensed forms of DNA - closed circular supercoils, toruses, chromatin.