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

The desorption of As from GaAs (001), (111)B, and AlAs(001) is studied in detail by measuring the electron‐beam current reflected from these surfaces. When the As supply to the surface was terminated, the electron specular reflectivity decreases exponentially with time due to the As desorption. The decay rate was much smaller for AlAs (001) than for GaAs (001) and (111)B, which indicates stronger atomic bonding for AlAs than for GaAs. For the GaAs (001) surface, the decay rate and the activation energy for the decay in specular reflectivity change discontinuously at the transition between (2×4) and (3×1) reconstructions. This shows the As desorption process is sensitive to the transition of surface reconstruction. The dependence of the As desorption rate on the thickness of the top GaAs layer in GaAs/AlAs heterostructures indicates an abrupt change of bond strength near the interface.

As desorption from GaAs and AlAs surfaces studied by improved high‐energy electron reflectivity measurements

Step motion and As desorption on InAs(001) surfaces are directly observed by scanning tunneling microscopy at high temperatures. Stable (2\ifmmode\times\else\texttimes\fi{}4) structures are observed even at temperatures high enough to cause the motion of monomolecular steps and kinks. At higher temperatures, domains with dark contrast (As-desorbed regions) are clearly observed. These results differ from those for GaAs surfaces and indicate strong lateral interaction in (2\ifmmode\times\else\texttimes\fi{}4) structures on InAs.

Step motion and As desorption on InAs(001) surfaces observed by scanning tunneling microscopy.

Cilazapril (CLZ) has been reported to reduce intimal hyperplasia in a rat carotid model of restenosis. The purpose of this study was to determine whether CLZ inhibits restenosis after deep arterial injury in lathyritic rats. The lathyritic rat was used as a model of deep arterial injury; in this model the internal elastic lamina is easily broken by balloon injury because of the fragility of the connective tissue. Deep arterial injury is defined as rupture of the internal elastic lamina with damage to both the intima and the media. The rats were divided into 4 groups (n = 40): mild injury (intimal damage with intact internal elastic lamina), mild injury +CLZ, deep injury, and deep injury +CLZ. In the CLZ-treated groups, the drug was administered orally (10 mg/day) from 7 days before balloon injury until the time of sacrifice 21 days after balloon injury. The intimal hyperplasia was determined histologically using a computerized morphometry program. At sacrifice, blood pressure was lower in the CLZ-treated groups than in the untreated (control) rats (p < 0.05). In the mild injury model, CLZ decreased intimal hyperplasia markedly. In contrast, CLZ failed to reduce intimal hyperplasia in the rats with deep injury. CLZ markedly decreased neointimal hyperplasia in mild injury. In contrast, CLZ failed to reduce intimal area in deep injury. The type of arterial injury seems to determine the effectiveness of CLZ.

Limitations of Angiotensin-Converting Enzyme Inhibitor in Restenosis of a Deep Arterial Injury Model

Three-dimensional (3D) alignment with 10nm order accuracy in 3D electron-beam (EB) lithography has been achieved by means of highly accurate rotation control and mark location using the transmission electron signal Accurately aligned EB writing from various directions on micron order resists blocks on a small substrate provides great structural flexibility in the creation of 3D nanostructures As a demonstration of the accuracy, a 3D hydrogen silsesquioxane nanostructure was made by 3D EB writing and two-step development using different developers Moreover, a 3D poly(methyl methacrylate) nanostructure was made by repeated 3D EB writing and development to demonstrate 3D nanofabrication with great structural flexibility

Three-dimensional alignment with 10nm order accuracy in electron-beam lithography on rotated sample for three-dimensional nanofabrication

An electromechanical oscillator embedded with a two dimensional electron gas is capacitively coupled to a silicon field effect transistor (Si-FET). The piezovoltage induced by the mechanical motion modulates the current passing through the Si-FET enabling the electromechanical oscillator’s position to be monitored. When the Si-FET is biased at its optimal point, the motion induced piezovoltage can be amplified resulting in a displacement sensitivity of 6×10−12 mHz−1/2 for a 131 kHz GaAs resonator which is among the highest recorded for an all-electrical room temperature detection scheme.

Hiroshi Yamaguchi

Papers

As desorption from GaAs and AlAs surfaces studied by improved high‐energy electron reflectivity measurements

Step motion and As desorption on InAs(001) surfaces observed by scanning tunneling microscopy.

Limitations of Angiotensin-Converting Enzyme Inhibitor in Restenosis of a Deep Arterial Injury Model

Three-dimensional alignment with 10nm order accuracy in electron-beam lithography on rotated sample for three-dimensional nanofabrication

Room temperature piezoelectric displacement detection via a silicon field effect transistor