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

His-PurkinJe系におけるWenokebaoh型房室ブロック10例 (ヒス束内ブロック6例, ヒス束遠位 (H-V) ブロック4例) の臨床電気生理学的特徴を検討した.(1) Wenokebaoh型房室ブロックは, 洞調律時, 心房ペーシング時ともに毎分100以下の心房拍数で出現した.(2) WenokebaGh周期中のブロック後第1拍目よりQRS波脱落直前までの房室伝導時間の延長の様式は, 房室結節内 (A-H) ブロックとの鑑別に有用でなかった.(3) 硫酸アトロピンもしくは運動負荷における房室伝導は, 全例負荷後2度以上の房室ブロックを呈し, 不変であった1例を除く全例で悪化した.(4) 全例で徐脈による症状, およびより高度な房室ブロックへの進展を認め, ペースメーカー治療を要した.Wenokebach型房室ブロックであっても, 徐脈による症状を伴い, 硫酸アトロピンもつしくは運動負荷後も2度以上の房室ブロックを呈する例では, His-Purkinje系の伝導障害が疑われ, ペースメーカー治療の必要性が示唆された.

https://www.jstage.jst.go.jp/article/jse1981/16/1/16_1_1/_pdf

Wenckebach Type Second Degree Atrioventricular Block in the His-Purkinje System

We measured the magneto-piezoresistance of micromechanical cantilevers fabricated from two-dimensional InAs/AlGaSb heterostructures. The magneto-piezoresistance showed the features of conductance fluctuation and Schbnikov–de Haas oscillation, depending on the sample electron mobility, indicating strong quantum effects on the piezoresistance. A possible mechanism for these quantum effects is discussed based on the comparison between the magneto-piezoresistance and differential magnetoresistance curves.

Piezoresistive cantilevers using InAs-based 2D Heterostructures

We analyze in detail a new ''dipole'' mechanism of spontaneous N = 2 supersymmetry breaking free from Goldstone-fermion difficulties, with the final result of ''explicit'' but finiteness-preserving soft breakings of N = 2 supersymmetry. It is explicitly demonstrated how the massless poles of unphysical Goldstone fermions produce the mass splittings without contradicting conservation of supercurrents. It is also shown that the bound on central charges derived on the basis of positivity of metrics is violated in this type of model.

Dipole mechanism of spontaneous breaking of N=2 supersymmetry: Violation of positivity bound on central charges

W. Izumida,1,* Y. Hirayama,1,2 H. Okamoto,3 H. Yamaguchi,1,3 and K.-J. Friedland4 1Department of Physics, Tohoku University, Sendai 980-8578, Japan 2ERATO Nuclear Spin Electronics Project, Sendai 980-8578, Japan 3NTT Basic Research Laboratories, NTT Corporation, 3-1 Morinosato-Wakamiya, Atsugi 243-0198, Japan 4Paul-Drude-Institut fur Festkorperelektronik, Hausvogteiplatz 5-7, D-10117 Berlin, Germany (Received 14 August 2011; revised manuscript received 21 December 2011; published 14 February 2012)

Mechanical vibration of a cylindrically rolled-up cantilever shell in microelectromechanical and nanoelectromechanical systems

GABAergic neurons in the ventral tegmental area (VTA) have brain-wide projections and are involved in multiple behavioral and physiological functions. Here, we revealed the responsiveness of Gad67+ neurons in VTA (VTAGad67+) to various neurotransmitters involved in the regulation of sleep/wakefulness by slice patch clamp recording. Among the substances tested, a cholinergic agonist activated, but serotonin, dopamine and histamine inhibited these neurons. Dense VTAGad67+ neuronal projections were observed in brain areas regulating sleep/wakefulness, including the central amygdala (CeA), dorsal raphe nucleus (DRN), and locus coeruleus (LC). Using a combination of electrophysiology and optogenetic studies, we showed that VTAGad67+ neurons inhibited all neurons recorded in the DRN, but did not inhibit randomly recorded neurons in the CeA and LC. Further examination revealed that the serotonergic neurons in the DRN (DRN5–HT) were monosynaptically innervated and inhibited by VTAGad67+ neurons. All recorded DRN5–HT neurons received inhibitory input from VTAGad67+ neurons, while only one quarter of them received inhibitory input from local GABAergic neurons. Gad67+ neurons in the DRN (DRNGad67+) also received monosynaptic inhibitory input from VTAGad67+ neurons. Taken together, we found that VTAGad67+ neurons were integrated in many inputs, and their output inhibits DRN5–HT neurons, which may regulate physiological functions including sleep/wakefulness.

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Hiroshi Yamaguchi

Papers

Wenckebach Type Second Degree Atrioventricular Block in the His-Purkinje System

Piezoresistive cantilevers using InAs-based 2D Heterostructures

Dipole mechanism of spontaneous breaking of N=2 supersymmetry: Violation of positivity bound on central charges

Mechanical vibration of a cylindrically rolled-up cantilever shell in microelectromechanical and nanoelectromechanical systems

Functional Interaction Between GABAergic Neurons in the Ventral Tegmental Area and Serotonergic Neurons in the Dorsal Raphe Nucleus