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

Nanomechanical devices fabricated from semiconductor nanowire are expected to be used in various applications such as many kinds of sensors and also the study of fundamental physics such like macroscopic quantum phenomena. We made such devices of InAs nanowire by developing a novel fabrication method by using inkjet printing for precise assembling of nanowire-dispersed droplets and by forming a PMGI sacrificial layer for suspending nanowire. This method allows the fabrication of highly sophisticated structures such like the quantum dot coupled with a nanomechanical system. We measured mechanical property in this device by using RF mixing technique and observed mechanical resonance around 12.8MHz with the quality factor of 750 at room temperature. This resonance showed duffing nonlinearity when we applied higher AC gate voltage to actuate vibration of nanowire. We observed not only mechanical property but also UCF (universal conductance fluctuation) in the low temperature transport measurement, which is the specific characteristics of one dimensional material, in another device similarly fabricated using the same method. As already reported in the top-down structures, the one-dimensional magnetoresistance can be used for sensitively detecting nanowire vibration and pave the way to realize highly functional quantum hybrid devices of mechanical motion and quantum carrier transport.

Novel Fabrication Technique of Suspended Nanowire Devices for Nanomechanical Applications

We herein present a case of a 33-year-old woman who was referred to our hospital for dyspnea on effort 2 months before her admission. Although diffuse enlargement of the thyroid gland occurred at the age of 23, she did not undergo detailed medical examinations. She was diagnosed with hyperthyroidism due to Graves’ disease, and the administration of methimazole was initiated at a dosage of 30 mg/day. She had congestive heart failure, rapid atrial fibrillation, and disseminated intravascular coagulation on admission. Thyroid crisis was diagnosed based on the diagnostic criteria of the Japan Endocrine Society (second edition). Although cardiac function and heart failure symptoms improved, her total bilirubin level continued to increase and peaked at 28.8 mg/dL. Her bilirubin level was reduced by anti-thyroid drugs and eventually normalized in parallel with improvements in thyroid function. Jaundice may have occurred as a secondary consequence of cholestasis due to hyperthyroidism because other causes such as drug-induced or autoimmune liver dysfunction were ruled out. We herein report a rare case of thyroid crisis with worsening jaundice despite improvements in heart failure. This case demonstrated that obtaining a detailed medical history and a careful examination of the clinical course were useful for reaching the differential diagnosis of severe jaundice and achieving steady improvements in this serious medical condition. J Endocrinol Metab. 2016;6(2):59-63 doi: http://dx.doi.org/10.14740/jem345w

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A Case of Thyroid Crisis With Worsening Jaundice Despite Improvements in Heart Failure

In situ observation of MEE GaAs growth using scanning electron microscopy

Unified model for first-order transition and electrical properties of InAs (001) surfaces based on atom-resolved scanning tunneling microscopy imaging

We studied the structural, electrical, and mechanical properties of an InAs thin film grown on GaAs (111)A substrates by molecular beam epitaxy. In contrast to conventionally used (001) surfaces, where Stranski-Krastanovgrowth dominates the highly mismatched heteroepitaxy, layer-by-layer growth of InAs can be established. One of the largest advantages of this unique heteroepitaxial system is that it provides a two-dimensional electron gas system in the near-surface region without the problem of electron depletion. We review the fundamental properties and applications of this unique heteroepitaxial system.

Hiroshi Yamaguchi

Papers

Novel Fabrication Technique of Suspended Nanowire Devices for Nanomechanical Applications

A Case of Thyroid Crisis With Worsening Jaundice Despite Improvements in Heart Failure

In situ observation of MEE GaAs growth using scanning electron microscopy

Unified model for first-order transition and electrical properties of InAs (001) surfaces based on atom-resolved scanning tunneling microscopy imaging

InAs/GaAs (111)A heteroepitaxial systems