The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Copper is an essential trace element in living systems, present in the parts per million concentration range. It is a key cofactor in a diverse array of biological oxidation-reduction reactions. These involve either outer-sphere electron transfer, as in the blue copper proteins and the Cu{sub A} site of cytochrome oxidase and nitrous oxide redutase, or inner-sphere electron transfer in the binding, activation, and reduction of dioxygen, superoxide, nitrite, and nitrous oxide. Copper sites have historically been divided into three classes based on their spectroscopic features, which reflect the geometric and electronic structure of the active site: type 1 (T1) or blue copper, type 2 (T2) or normal copper, and type 3 (T3) or coupled binuclear copper centers. 428 refs.

Multicopper Oxidases and Oxygenases

Denitrification is a distinct means of energy conservation, making use of N oxides as terminal electron acceptors for cellular bioenergetics under anaerobic, microaerophilic, and occasionally aerobic conditions. The process is an essential branch of the global N cycle, reversing dinitrogen fixation, and is associated with chemolithotrophic, phototrophic, diazotrophic, or organotrophic metabolism but generally not with obligately anaerobic life. Discovered more than a century ago and believed to be exclusively a bacterial trait, denitrification has now been found in halophilic and hyperthermophilic archaea and in the mitochondria of fungi, raising evolutionarily intriguing vistas. Important advances in the biochemical characterization of denitrification and the underlying genetics have been achieved with Pseudomonas stutzeri, Pseudomonas aeruginosa, Paracoccus denitrificans, Ralstonia eutropha, and Rhodobacter sphaeroides. Pseudomonads represent one of the largest assemblies of the denitrifying bacteria within a single genus, favoring their use as model organisms. Around 50 genes are required within a single bacterium to encode the core structures of the denitrification apparatus. Much of the denitrification process of gram-negative bacteria has been found confined to the periplasm, whereas the topology and enzymology of the gram-positive bacteria are less well established. The activation and enzymatic transformation of N oxides is based on the redox chemistry of Fe, Cu, and Mo. Biochemical breakthroughs have included the X-ray structures of the two types of respiratory nitrite reductases and the isolation of the novel enzymes nitric oxide reductase and nitrous oxide reductase, as well as their structural characterization by indirect spectroscopic means. This revealed unexpected relationships among denitrification enzymes and respiratory oxygen reductases. Denitrification is intimately related to fundamental cellular processes that include primary and secondary transport, protein translocation, cytochrome c biogenesis, anaerobic gene regulation, metalloprotein assembly, and the biosynthesis of the cofactors molybdopterin and heme D1. An important class of regulators for the anaerobic expression of the denitrification apparatus are transcription factors of the greater FNR family. Nitrate and nitric oxide, in addition to being respiratory substrates, have been identified as signaling molecules for the induction of distinct N oxide-metabolizing enzymes.

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Cell biology and molecular basis of denitrification.

Graphene, a single monolayer of graphite, has recently attracted considerable interest owing to its novel magneto-transport properties, high carrier mobility and ballistic transport up to room temperature. It has the potential for technological applications as a successor of silicon in the post Moore's law era, as a single-molecule gas sensor, in spintronics, in quantum computing or as a terahertz oscillator. For such applications, uniform ordered growth of graphene on an insulating substrate is necessary. The growth of graphene on insulating silicon carbide (SiC) surfaces by high-temperature annealing in vacuum was previously proposed to open a route for large-scale production of graphene-based devices. However, vacuum decomposition of SiC yields graphene layers with small grains (30-200 nm; refs 14-16). Here, we show that the ex situ graphitization of Si-terminated SiC(0001) in an argon atmosphere of about 1 bar produces monolayer graphene films with much larger domain sizes than previously attainable. Raman spectroscopy and Hall measurements confirm the improved quality of the films thus obtained. High electronic mobilities were found, which reach mu=2,000 cm (2) V(-1) s(-1) at T=27 K. The new growth process introduced here establishes a method for the synthesis of graphene films on a technologically viable basis.

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Towards wafer-size graphene layers by atmospheric pressure graphitization of silicon carbide

For present purposes, a protein-bound metal site consists of one or more metal ions and all protein side chain and exogenous bridging and terminal ligands that define the first coordination sphere of each metal ion. Such sites can be classified into five basic types with the indicated functions: (1) structural -- configuration (in part) of protein tertiary and/or quaternary structure; (2) storage -- uptake, binding, and release of metals in soluble form: (3) electron transfer -- uptake, release, and storage of electrons; (4) dioxygen binding -- metal-O{sub 2} coordination and decoordination; and (5) catalytic -- substrate binding, activation, and turnover. The authors present here a classification and structure/function analysis of native metal sites based on these functions, where 5 is an extensive class subdivided by the type of reaction catalyzed. Within this purview, coverage of the various site types is extensive, but not exhaustive. The purpose of this exposition is to present examples of all types of sites and to relate, insofar as is currently feasible, the structure and function of selected types. The authors largely confine their considerations to the sites themselves, with due recognition that these site features are coupled to protein structure at all levels. In themore » next section, the coordination chemistry of metalloprotein sites and the unique properties of a protein as a ligand are briefly summarized. Structure/function relationships are systematically explored and tabulations of structurally defined sites presented. Finally, future directions in bioinorganic research in the context of metal site chemistry are considered. 620 refs.« less

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Structural and Functional Aspects of Metal Sites in Biology

Monocrystalline GaAs/ErAs/GaAs structures are fabricated by migration‐enhanced epitaxy at 320 °C. When the ErAs layer thickness is less than 3 monolayers, reflection high‐energy electron diffraction patterns, double crystal x‐ray diffraction analysis, and transmission electron microscopy observations show successful overgrowth of GaAs on the ErAs layer. Distinct satellite peaks are observed in an x‐ray rocking curve of an ErAs/GaAs superlattice grown under a similar condition, indicating that high‐quality multilayer structures with very thin ErAs layers can be fabricated by migration‐enhanced epitaxy.

Growth of GaAs/ErAs/GaAs structures by migration‐enhanced epitaxy

When we use a scanning electron microscope-molecular beam epitaxy system with a GaAs (111)A substrate that dramatically improves the flatness of the growing surface, it makes possible detailed observations of the near-equilibrium growth processes of island nucleation, coalescence, and step motion. These observations allow the quantitative analysis of the growth processes based on the standard model of crystal growth. As an example, the Ga adatom surface diffusion length is directly determined from the dependence of measured step velocity on the Ga arrival rate.

Imaging of layer by layer growth processes during molecular beam epitaxy of GaAs on (111)A substrates by scanning electron microscopy

We investigate the dynamics of a microelectromechanical self-sustained oscillator supporting multiple resonating and interacting modes. In particular, the interaction of the first four flexural modes along with the first torsional mode are studied, whereby 1:2, 1:3, and 2:1 internal resonances occur. Even and odd modes are induced to couple by breaking the longitudinal symmetry of the structure. Self-oscillations are induced in the second flexural mode via a gain-feedback loop; thereafter its frequency is pulled into a commensurate frequency ratio with the other modes, enabling the oscillator to act as a driver or pump for four modes simultaneously.

Demonstration of Multiple Internal Resonances in a Microelectromechanical Self-Sustained Oscillator

The high-quality-factor mechanical resonator in electromechanical systems has facilitated dynamic control of phonons via parametric nonlinear processes and paved the development of mechanical logic-elements. However the resonating element with a narrow bandwidth limits the resultant operation speeds as well as constraining the availability of nonlinear phenomena to a narrow spectral range. To overcome these drawbacks we have developed phonon waveguides in which the mechanical analogue of four-wave-mixing is demonstrated that enables the frequency of phonon waves to be converted over 1 MHz. We harness this platform to execute multiple binary mechanical logic gates in parallel, via frequency division multiplexing in a two-octave-wide phonon transmission band, where each gate can be independently reconfigured. The fidelity of the binary gates is verified via temporal measurements yielding eye diagrams which confirm the availability of high speed logic operations. The phonon waveguide architecture thus offers the broadband functionality that is essential to realising mechanical signal processors.

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Broadband reconfigurable logic gates in phonon waveguides

Reflection high-energy electron diffraction is observed during the growth of GaAs, AlGaAs, and InAs by migration-enhanced epitaxy on misoriented (100) substrates. The influence of an As-free atmosphere during Ga deposition in migration-enhanced epitaxy on step-flow growth is examined. Measurements of the change in specular peak intensity show that an As-free atmosphere accelerates step-flow growth, and that the ease with which step-flow growth occurs follows the order of InAs, GaAs, and AlGaAs. On the other hand, measurements of the specular peak width of the diffraction intensity profiles show that uniform step structures can be obtained for GaAs and AlGaAs layers under the same conditions if a small amount of As pressure is added during the metallic atom deposition in the process of migration-enhanced epitaxy.

Hiroshi Yamaguchi

Papers

Growth of GaAs/ErAs/GaAs structures by migration‐enhanced epitaxy

Imaging of layer by layer growth processes during molecular beam epitaxy of GaAs on (111)A substrates by scanning electron microscopy

Demonstration of Multiple Internal Resonances in a Microelectromechanical Self-Sustained Oscillator

Broadband reconfigurable logic gates in phonon waveguides

Influence of an As-Free Atmosphere in Migration-Enhanced Epitaxy on Step-Flow Growth