bluuebunny/crossref_metadata_2025 huggingface dataset:
(Invited) High-Performance Top-Gate and Double-Gate Low-Temperature Polycrystalline-Silicon Thin-Film Transistors Fabricated Using Continuous-Wave-Laser Lateral Crystallization on a Glass Substrate
Authors: Hara Akito , Meguro Tatsuya , Sasaki Shun , Ohsawa Hiroki
Published: May 2015

A high-quality polycrystalline silicon (poly-Si) film is a technology for improving the performance of low-temperature (LT) poly-Si thin-film transistors (TFTs). We have already developed continuous-wave-laser lateral crystallization (CLC) using a diode-pumped solid-state laser to improve the crystalline quality of the thin poly-Si film. In this paper, we report on two approaches for improving the performance of LT poly-Si TFTs, which are based on a thin CLC poly-Si film and are fabricated at 550 ºC on a glass substrate. The first approach is a combination of a CLC poly-Si film and sputtered HfO2 as the gate dielectric. The other approach is a combination of a CLC poly-Si film and a double-gate structure for realizing four-terminal LT poly-Si TFTs. The former exhibited an enhancement in the on-current that was four times greater than a device with a silicon dioxide gate stack. In the latter, high controllability of the threshold voltage was confirmed.
Bulk Barrier Source-Gated Transistors with Improved Drain Current Dynamic Range and Temperature Coefficient
Authors: Sporea Radu Alexandru , Wright William , Shannon John M , Silva S. Ravi P.
Published: May 2015

Source-gated thin-film transistors (SGTs) have remarkable properties related to low-voltage amplification, tolerance to process variation and electrical stability. They rely on a potential barrier at the source in their operation, and usually this barrier is realized through a Schottky contact. Here, we study SGTs with source barriers made by doping the source region of the semiconductor to form bulk unipolar diodes (BUD). A BUSGT can have much higher drain current with a lower activation energy, resulting in higher switching speed and improved transconductance. Barriers made via doping also provide a wider range of barrier heights compared with Schottky contacts. We discuss design parameters for BUSGTs and compare these devices with SBSGTs.
(Invited) Metal-Insulator-Metal Devices with High-K Dielectric for Nonvolatile or Dynamic Random Access Memories
Authors: Bsiesy Ahmad , Gonon Patrice , Vallée Christophe , Pointet John , Mannequin Cédric
Published: May 2015

This paper presents an overview of our work on metal-insulator-metal (MIM) structures used for resistive non-volatile resistive (RRAM) or dynamic (DRAM) random access memories. Atomic layer deposition technique is used to grow the insulator layer. ALD allows monolayer thickness precision of deposited layers and flexible in-situ doping capabilities. Thanks to a suitable choice of the bottom, top electrodes and the dielectric, DRAM or RRAM functionality is enabled. It will be shown how we managed to tackle the main challenge in DRAM field where high dielectric constant along with minimum leakage current should be performed. For RRAM, the main challenge is to obtain reversible MIM resistance switching at low power and high Roff/Ron ratio. The switching mechanism in RRAM, usually attributed to oxygen vacancies percolation leading to a conduction path, has been studied with a focus on the role of the electrodes affinity to oxygen and their electron injection efficiency.
(Invited) Opportunities of High Performance Ge CMOS
Authors: Toriumi Akira
Published: May 2015

Ge is not a new material but now spotlighted for beyond Si-scaled CMOS. Ge p-MOSFETs have been well investigated and its high performance has so far been demonstrated. On the contrary, an achievement of high electron mobility Ge n-MOSFETs is quite challenging due to a large amount of interface states near the conduction band edge. So, we first discuss how to overcome “intrinsic challenges in Ge n-MOSFETs” from thermodynamic viewpoint of GeO2 on Ge. A very low Dit
(<1011 eV-1cm-2) at Ge/GeO2 interface and a very high peak electron mobility in Ge n-MOSFETs are presented. This is further extended to scaled gate stacks on Ge by controlling the oxygen potential of dielectric films on Ge.
(Invited) Advanced Germanium Epitaxy for Photonics Application
Authors: Yamamoto Yuji , Lischke Stefan , Zimmermann Lars , Knoll Dieter , Murota Junichi , Tillack Bernd
Published: May 2015

Investigations of low threading dislocation density (TDD) Ge growth using reduced pressure chemical vapor deposition for photonics application are reviewed. By interrupting the Ge growth process and annealing for several times during Ge epitaxy (cyclic annealing), TDD of below 1×106 cm-2 is achieved for 4.7 µm thick Ge. Root mean square of roughness below 0.5 nm is realized. Thin and low TDD Ge layer fabrication is demonstrated by depositing thick Ge with cyclic annealing process followed by HCl etching. Dislocation-free area of local Ge on insulator is formed between [110] and [1-10] direction by lateral selective Ge growth in cavity between SiO2 cap and buried oxide, which is formed by sacrificial Si etching. Using an atomic-layer-doping approach, self-limitation of incorporated P dose at ~1/4 monolayer is obtained offering heavy n-doping in Ge. P diffusion suppression by delta-doped Si in Ge is observed. By Ge growth followed by HCl etching process, photodiode with one order of magnitude lower dark current compared to standard Ge growth with cyclic annealing is fabricated.
(Invited) Atomically Controlled Processing for Germanium-Based CVD Epitaxial Growth
Authors: Murota Junichi , Yamamoto Yuji , Tillack Bernd
Published: May 2015

Introduction of Ge into ULSIs has become increasingly attractive because of the higher carrier mobility of Ge. Here, the reactions between Ge oxide and Si substrate or SiH4 in order to perform high quality Ge epitaxial growth and atomic-order surface nitridation of Ge/Si0.5Ge0.5/Si (100) heterostructure by NH3 are investigated. It is found that, by the adsorption of the Ge oxide on Si(100) surface, pure Ge and Si oxide are formed on the surface even at 400°C, and that, by SiH4 treatment at 350°C, the amount of the oxidized Ge decreases and Si oxide is formed on the Ge layer. On the nitridation of the heterostructure, it is found that N atoms diffuse through nm-order thick Ge layer into Si0.5Ge0.5/Si(100) substrate and form Si nitride even at 500°C. These results demonstrate the capability of CVD technology for atomically controlled processing of group IV semiconductors for ultra-large-scale integration.
(Invited) The Multidisciplinary Approach: A Common Trend for ULSI and Thin Film Technology
Authors: Bonnaud Olivier
Published: May 2015

The scaling down of microelectronics devices has been following the Moore’s law since many years. The capability of integration till increasing, the new integration more and more combines the devices and circuits to other than electrical functions, physical, chemical, or biological functions. These new objects need a multidisciplinary approach to insert the new devices in systems, in terms of applications. The fields of application can be very wide and should answer to the societal needs. The corresponding objects are preferentially communicating and smart in many cases. The design of these objects must combine the traditional electronics with digital circuits, the interface with the humans thanks to displays, but also many other functions of detections, communications, transmissions, signal treatments and actuations. This paper tries to show the diversity of the technologies, from ULSI to TFTs, able to answer to this new trend and gives some directions in order to well form the future engineers and researchers.
(Plenary) Wide Band Gap Semiconductor Transistors for FPD
Authors: Hwang Chi-Sun , Nam Eun-Soo
Published: May 2015

Wide band gap metal oxide semiconductor TFTs will play a major role in the development of the high resolution and high performance flat panel display. Metal oxide semiconductor TFTs with high mobility and good stability were developed at ETRI through extensive investigation of the materials, device structure, and interface engineering.
(Invited) Graphene Heat Spreaders and Interconnects for Advanced Electronic Applications
Authors: Balandin Alexander
Published: May 2015

Graphene revealed a number of unique properties beneficial for electronics, including exceptionally high electron mobility and widely tunable Fermi level. However, graphene does not have an electron energy band gap, which presents a serious hurdle for its applications in digital electronics. A possible route for practical use of graphene in electronics is utilization of its exceptionally high thermal conductivity and electron current conducting properties. This invited review outlines the thermal properties of graphene and describes prospective graphene technologies that are not affected by the absence of the energy band gap. The specific examples include heat spreaders, thermal coatings, high-current density electrodes and interconnects. Our results suggest that the thermal management of advanced electronic devices can become the first industry scale application of graphene.
(Invited) Hetero Interface of Ionic/Covalent Oxides for Nano-Electronics
Authors: Nabatame Toshihide
Published: May 2015

We investigated the role of hetero interface of ionic high-k and covalent SiO2 on flatband voltage (V
fb) and threshold voltage (V
th) shifts for CMOS and TFT. The V
fb and V
th of CMOS and TFT including high-k/SiO2 gate insulator were influenced due to the bottom interface dipole which causes at high-k/SiO2 interface. It is clear from experimental results that the direction and strength of the dipole moment strongly depend on oxygen concentration at high-k/SiO2 interface. We also found that GIZO TFTs with an Al2O3/SiO2 gate insulator exhibited positive V
th shift, electron mobility degradation by the fixed charge at Al2O3/GIZO interface and the bottom interface dipole at Al2O3/SiO2 interface. The hetero interface of high-k and SiO2 layers is very important not only for recognizing the mechanism of V
fb and V
th shifts but also for designing nano-electronic devices with high-k/SiO2 stack structure.
(Invited) A Diode-Like Antifuse Device Made of High-K Dielectric
Authors: Kuo Yue
Published: May 2015

Characteristics of a new type of antifuse device that has the MOS structure with a metal oxide high-k gate dielectric on a p-type Si have been investigated. Different from other antifuses, the on-set of the new device is determined by the breakdown voltage that is adjustable with the thickness or material properties of the high-k stack. A high current ratio of 105 between the “programed” and “unprogrammed” states was achieved. This device also behaves like a diode that allows the current to flow in one direction but not the opposite direction. The new device is fabricated from IC processes and materials. It is applicable to various products.
(Invited) Wavy Channel TFT Architecture for High Performance Oxide Based Displays
Authors: Hanna Amir N. , Hussain Aftab M. , Ghoneim Mohamed T. , Rojas Jhonathan P , Torres Sevilla Galo A. , Hussain Muhammad M.
Published: May 2015

We show the effectiveness of wavy channel architecture for thin film transistor application for increased output current. This specific architecture allows increased width of the device by adopting a corrugated shape of the substrate without any further real estate penalty. The performance improvement is attributed not only to the increased transistor width, but also to enhanced applied electric field in the channel due to the wavy architecture.
An Organic Device with Thin Film Transistor Merged with Light Emitting Diode through Use of an Accumulation Layer in TFT As an Electrode
Authors: Gangwar Ankita , Mazhari Baquer
Published: May 2015

A light-emitting device structure is proposed which includes an organic thin-film structure merged with an organic light-emitting diode structure by utilizing a part of the electron accumulation layer in the organic thin-film transistor as a common electrode for each structure. The organic thin-film structure and the organic light-emitting diode structure each include an organic semiconductor material in which hole mobility is greater in bulk region of the material than electron mobility in the bulk region but less in the channel region. The advantages of such a light-emitting device include less complex processing and a simpler pixel circuit structure in comparison to separately fabricating OTFT and OLED structures and subsequently interconnecting them to form a pixel. Furthermore, relative to a light-emitting transistor, the proposed structure offers the advantage of a broader light emission area which is more suitable for use in display devices.
(Invited) Leakage Current Reduction in ALD-Al2O3 Dielectric Deposited on Si by High Pressure Deuterium Oxide Annealing
Authors: Yoshitsugu Koji , Horita Masahiro , Ishikawa Yasuaki , Uraoka Yukiharu
Published: May 2015

This paper reports an effect of post annealing technique for the deposited dielectric films utilizing high pressure deuterium oxide. Al2O3 deposited on Si thermal oxide film by plasma-assisted atomic layer deposition (PA-ALD), which can have the advantage of low temperature process. For reforming qualities of the ALD–Al2O3, high pressure deuterium oxide annealing (HPDOA) was carried out at 0.3 MPa for 60 min while keeping at 300ºC. The leakage current and the breakdown field of metal-insulator-semiconductor (MIS) diodes with the Al2O3 gate dielectrics were improved by the HPDOA treatment. The HPDOA is found to be useful for reforming the Al2O3 thin film even if it was deposited by PA-ALD.
Load-dependent extracellular matrix organization in atrioventricular heart valves: differences and similarities
Authors: Alavi S. Hamed , Sinha Aditi , Steward Earl , Milliken Jeffrey C. , Kheradvar Arash
Published: May 2015

The extracellular matrix of the atrioventricular (AV) valves' leaflets has a key role in the ability of these valves to properly remodel in response to constantly varying physiological loads. While the loading on mitral and tricuspid valves is significantly different, no information is available on how collagen fibers change their orientation in response to these loads. This study delineates the effect of physiological loading on AV valves' leaflets microstructures using Second Harmonic Generation (SHG) microscopy. Fresh natural porcine tricuspid and mitral valves' leaflets ( n = 12/valve type) were cut and prepared for the experiments. Histology and immunohistochemistry were performed to compare the microstructural differences between the valves. The specimens were imaged live during the relaxed, loading, and unloading phases using SHG microscopy. The images were analyzed with Fourier decomposition to mathematically seek changes in collagen fiber orientation. Despite the similarities in both AV valves as seen in the histology and immunohistochemistry data, the microstructural arrangement, especially the collagen fiber distribution and orientation in the stress-free condition, were found to be different. Uniaxial loading was dependent on the arrangement of the fibers in their relaxed mode, which led the fibers to reorient in-line with the load throughout the depth of the mitral leaflet but only to reorient in-line with the load in deeper layers of the tricuspid leaflet. Biaxial loading arranged the fibers in between the two principal axes of the stresses independently from their relaxed states. Unlike previous findings, this study concludes that the AV valves' three-dimensional extracellular fiber arrangement is significantly different in their stress-free and uniaxially loaded states; however, fiber rearrangement in response to the biaxial loading remains similar.
Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension
Authors: Natali Antonio J. , Fowler Ewan D. , Calaghan Sarah C. , White Ed
Published: May 2015

Increased physical activity is recommended for the general population and for patients with many diseases because of its health benefits but can be contraindicated if it is thought to be a risk for serious cardiovascular events. One such condition is pulmonary artery hypertension (PAH). PAH and right ventricular failure was induced in rats by a single injection of monocrotaline (MCT). MCT rats with voluntary access to a running wheel ran on average 2 km/day. The time for half the animals to develop heart failure signs (median survival time) was 28 days (exercise failure group), significantly longer than sedentary animals (sedentary failure group, 23 days). The contractility of single failing myocytes in response to increasing demand (stimulation frequency) was significantly impaired compared with that in both sedentary control and exercising control myocytes. However, myocytes from exercising MCT rats, tested at 23 days (exercise + MCT group), showed responses intermediate to the control (sedentary control and exercising control) and failing (sedentary failure and exercise failure) groups. We conclude that voluntary exercise is beneficial to rats with heart failure induced by PAH, and this is evidence to support the consideration of appropriate exercise regimes for potentially vulnerable groups.
Exercise training attenuates chemoreflex-mediated reductions of renal blood flow in heart failure
Authors: Marcus Noah J. , Pügge Carolin , Mediratta Jai , Schiller Alicia M. , Del Rio Rodrigo , Zucker Irving H. , Schultz Harold D.
Published: May 2015

In chronic heart failure (CHF), carotid body chemoreceptor (CBC) activity is increased and contributes to increased tonic and hypoxia-evoked elevation in renal sympathetic nerve activity (RSNA). Elevated RSNA and reduced renal perfusion may contribute to development of the cardio-renal syndrome in CHF. Exercise training (EXT) has been shown to abrogate CBC-mediated increases in RSNA in experimental heart failure; however, the effect of EXT on CBC control of renal blood flow (RBF) is undetermined. We hypothesized that CBCs contribute to tonic reductions in RBF in CHF, that stimulation of the CBC with hypoxia would result in exaggerated reductions in RBF, and that these responses would be attenuated with EXT. RBF was measured in CHF-sedentary (SED), CHF-EXT, CHF-carotid body denervation (CBD), and CHF-renal denervation (RDNX) groups. We measured RBF at rest and in response to hypoxia (FiO2 10%). All animals exhibited similar reductions in ejection fraction and fractional shortening as well as increases in ventricular systolic and diastolic volumes. Resting RBF was lower in CHF-SED (29 ± 2 ml/min) than in CHF-EXT animals (46 ± 2 ml/min, P < 0.05) or in CHF-CBD animals (42 ± 6 ml/min, P < 0.05). In CHF-SED, RBF decreased during hypoxia, and this was prevented in CHF-EXT animals. Both CBD and RDNX abolished the RBF response to hypoxia in CHF. Mean arterial pressure increased in response to hypoxia in CHF-SED, but was prevented by EXT, CBD, and RDNX. EXT is effective in attenuating chemoreflex-mediated tonic and hypoxia-evoked reductions in RBF in CHF.
ICAM-1-dependent and ICAM-1-independent neutrophil lung infiltration by porcine reproductive and respiratory syndrome virus infection
Authors: Liu Jie , Hou Make , Yan Meiping , Lü Xinhui , Gu Wei , Zhang Songlin , Gao Jianfeng , Liu Bang , Wu Xiaoxiong , Liu Guoquan
Published: May 2015

Neutrophils are innate immune cells that play a crucial role in the first line of host defense. It is also known that neutrophil lung recruitment and infiltration may cause lung injury. The roles of neutrophils in virus infection-induced lung injury are not clear. We explore the mechanisms of neutrophil lung infiltration and the potential biomarkers for lung injury in a swine model of lung injury caused by natural or experimental porcine reproductive and respiratory syndrome virus (PRRSV) infection. Neutrophil lung infiltration was determined by measurement of myeloperoxidase expression and enzyme activity of lung tissues. Myeloperoxidase expression and enzyme activity were dramatically increased in the naturally and experimentally infected lung tissues. Chemokine analysis by quantitative PCR and ELISA showed that IL-8 expression was increased in both infections, while monocyte chemoattractant protein-1 expression was increased only in experimentally infected lung tissues. Expression of the cell adhesion molecules VCAM-1 and ICAM-1 was measured by quantitative PCR and Western blotting. VCAM-1 expression was increased in experimentally and naturally infected lungs, whereas ICAM-1 expression was increased only in the naturally infected lung samples. Our results suggest that neutrophil lung infiltrations in the infected animals are both ICAM-1- and -independent and that combined expression of VCAM-1 and IL-8 may serve as the biomarker for lung injury induced by virus infection.
Time course of cigarette smoke-induced changes of systemic inflammation and muscle structure
Authors: Krüger K. , Dischereit G. , Seimetz M. , Wilhelm J. , Weissmann N. , Mooren F. C.
Published: May 2015

It has become more evident that long-term cigarette smoking (LTCS) has an important extrapulmonary toxicity. The aim of the study was to investigate the time-dependent effects of cigarette smoke exposure on exercise capacity, markers of systemic inflammation, and skeletal muscle structure. c57bl/6j-mice were either exposed to mainstream cigarette smoke for 6 h/day, 5 days/wk [smoke-exposed (SE) group] or assigned to the control, unexposed group (Con group). SE group mice were exposed for 8, 16, 24, and 32 wk to smoke and unexposed Con mice were used as age-matched controls. Exercise capacity was investigated by spiroergometry. Systemic inflammatory status was analyzed by flow cytometry and multiplexed fluorescent immunoassay. For analysis of muscle tissue, histological techniques and microarray analysis were used. Mice of the SE group exhibited a lower increase of body mass and a decrease of V̇o2 max( P < 0.05). An increase of lymphocyte CD62, ICAM, and VCAM expression was found in SE mice ( P < 0.05). A biphasic trend of protein up- and downregulation was observed in markers of systemic inflammation, tissue deterioration, and allergic reactions such as C-reactive protein (CRP), eotaxin, haptoglobin, macrophage colony-stimulating factor-1 (M-CSF-1), and macrophage inflammatory protein-1γ (MIP-1γ). Thereby, the expression of several chemotactic proteins in plasma correlated with their expression in muscle. A time-dependent decrease of muscle mass, oxidative type-I fibers, and muscle cross-sectional area was found ( P < 0.05). Microarray analysis revealed a SE-induced upregulation of several pathways of metabolic processes and tissue degradation. Taken together it was found that the loss of exercise capacity and systemic inflammation are early events of SE, which might induce muscular atrophy and loss of oxidative muscle capacity.
14-3-3 isoforms bind directly exon B of the 5′-UTR of human surfactant protein A2 mRNA
Authors: Noutsios Georgios T. , Ghattas Paul , Bennett Stephanie , Floros Joanna
Published: May 2015

Human surfactant protein (SP) A (SP-A), an innate immunity molecule, is encoded by two genes, SFTPA1 and SFTPA2. The 5′-untranslated splice variant of SP-A2 (ABD), but not SP-A1 (AD), contains exon B (eB). eB is an enhancer for transcription and translation and contains cis-regulatory elements. Specific trans-acting factors, including 14-3-3, bind eB. The 14-3-3 protein family contains seven isoforms that have been found by mass spectrometry in eB electromobility shift assays (Noutsios et al. Am J Physiol Lung Cell Mol Physiol 304: L722–L735, 2013). We used four different approaches to investigate whether 14-3-3 isoforms bind directly to eB. 1) eB RNA pulldown assays showed that 14-3-3 isoforms specifically bind eB. 2) RNA electromobility shift assay complexes were formed using purified 14-3-3 isoforms β, γ, ε, η, σ, and τ, but not isoform ζ, with wild-type eB RNA. 3 and 4) RNA affinity chromatography assays and surface plasmon resonance analysis showed that 14-3-3 isoforms β, γ, ε, η, σ, and τ, but not isoform ζ, specifically and directly bind eB. Inhibition of 14-3-3 isoforms γ, ε, η, and τ/θ with shRNAs in NCI-H441 cells resulted in downregulation of SP-A2 levels but did not affect SP-A1 levels. However, inhibition of 14-3-3 isoform σ was correlated with lower levels of SP-A1 and SP-A2. Inhibition of 14-3-3 isoform ζ/δ, which does not bind eB, had no effect on expression levels of SP-A1 and SP-A2. In conclusion, the 14-3-3 protein family affects differential regulation of SP-A1 and SP-A2 by binding directly to SP-A2 5′-UTR mRNA.
Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice
Authors: Lee Benjamin , Robinson Keven M. , McHugh Kevin J. , Scheller Erich V. , Mandalapu Sivanarayana , Chen Chen , Di Y. Peter , Clay Michelle E. , Enelow Richard I. , Dubin Patricia J. , Alcorn John F.
Published: May 2015

Suppression of type 17 immunity by type I interferon (IFN) during influenza A infection has been shown to enhance susceptibility to secondary bacterial pneumonia. Although this mechanism has been described in coinfection with gram-positive bacteria, it is unclear whether similar mechanisms may impair lung defense against gram-negative infections. Furthermore, precise delineation of the duration of type I IFN-associated susceptibility to bacterial infection remains underexplored. Therefore, we investigated the effects of preceding influenza A virus infection on subsequent challenge with the gram-negative bacteria Escherichia coli or Pseudomonas aeruginosa and the temporal association between IFN expression with susceptibility to Staphylococcus aureus challenge in a mouse model of influenza and bacterial coinfection. Here we demonstrate that preceding influenza A virus led to increased lung E. coli and P. aeruginosa bacterial burden, which was associated with suppression of type 17 immunity and attenuation of antimicrobial peptide expression. Enhanced susceptibility to S. aureus coinfection ceased at day 14 of influenza infection, when influenza-associated type I IFN levels had returned to baseline levels, further suggesting a key role for type I IFN in coinfection pathogenesis. These findings further implicate type I IFN-associated suppression of type 17 immunity and antimicrobial peptide production as a conserved mechanism for enhanced susceptibility to both gram-positive and gram-negative bacterial coinfection during influenza infection.
TP53 Silencing Bypasses Growth Arrest of BRAFV600E-Induced Lung Tumor Cells in a Two-Switch Model of Lung Tumorigenesis
Authors: Shai Anny , Dankort David , Juan Joseph , Green Shon , McMahon Martin
Published: May 2015

Lung carcinogenesis is a multistep process in which normal lung epithelial cells are converted to cancer cells through the sequential acquisition of multiple genetic or epigenetic events. Despite the utility of current genetically engineered mouse (GEM) models of lung cancer, most do not allow temporal dissociation of the cardinal events involved in lung tumor initiation and cancer progression. Here we describe a novel two-switch GEM model for BRAFV600E-induced lung carcinogenesis allowing temporal dissociation of these processes. In mice carrying a Flp recombinase-activated allele of Braf (BrafFA) in conjunction with Cre-regulated alleles of Trp53, Cdkn2a, or c-MYC, we demonstrate that secondary genetic events can promote bypass of the senescence-like proliferative arrest displayed by BRAFV600E-induced lung adenomas, leading to malignant progression. Moreover, restoring or activating TP53 in cultured BRAFV600E/TP53Null or BRAFV600E/INK4A-ARFNull lung cancer cells triggered a G1 cell-cycle arrest regardless of p19ARF status. Perhaps surprisingly, neither senescence nor apoptosis was observed upon TP53 restoration. Our results establish a central function for the TP53 pathway in restricting lung cancer development, highlighting the mechanisms that limit malignant progression of BRAFV600E-initiated tumors. Cancer Res; 75(15); 3167–80. ©2015 AACR.
Database and Informatic Challenges in Representing Both Diploid and Tetraploid Xenopus Species in Xenbase
Authors: Vize Peter D. , Liu Yu , Karimi Kamran
Published: May 2015

At the heart of databases is a data model referred to as a schema. Relational databases store information in tables, and the schema defines the tables and provides a map of relationships that show how the different table/data types relate to one another. In Xenbase, we were tasked to represent genomic, molecular, and biological data of both a diploid and tetraploid Xenopus species. When the database model was built over a decade ago, we had very little information on the nature of the X.laevis tetraploidization, but a Chado-based data model was proposed that could deal with the various forms of data in both species. Once the X.laevis genome was sequenced and annotated, it became clear that the data schema is very like the evolutionary schema that resulted in the X.laevis genome.
Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and Is Enhanced by Anti-miR33 in Atherosclerosis
Authors: Karunakaran Denuja , Thrush A. Brianne , Nguyen My-Anh , Richards Laura , Geoffrion Michele , Singaravelu Ragunath , Ramphos Eleni , Shangari Prakriti , Ouimet Mireille , Pezacki John P. , Moore Kathryn J. , Perisic Ljubica , Maegdefessel Lars , Hedin Ulf , Harper Mary-Ellen , Rayner Katey J.
Published: May 2015

Rationale:

Therapeutically targeting macrophage reverse cholesterol transport is a promising approach to treat atherosclerosis. Macrophage energy metabolism can significantly influence macrophage phenotype, but how this is controlled in foam cells is not known. Bioinformatic pathway analysis predicts that miR-33 represses a cluster of genes controlling cellular energy metabolism that may be important in macrophage cholesterol efflux.

Objective:

We hypothesized that cellular energy status can influence cholesterol efflux from macrophages, and that miR-33 reduces cholesterol efflux via repression of mitochondrial energy metabolism pathways.

Methods and Results:

In this study, we demonstrated that macrophage cholesterol efflux is regulated by mitochondrial ATP production, and that miR-33 controls a network of genes that synchronize mitochondrial function. Inhibition of mitochondrial ATP synthase markedly reduces macrophage cholesterol efflux capacity, and anti-miR33 required fully functional mitochondria to enhance ABCA1-mediated cholesterol efflux. Specifically, anti-miR33 derepressed the novel target genes PGC-1α, PDK4, and SLC25A25 and boosted mitochondrial respiration and production of ATP. Treatment of atherosclerotic
Apoe
−/−
mice with anti-miR33 oligonucleotides reduced aortic sinus lesion area compared with controls, despite no changes in high-density lipoprotein cholesterol or other circulating lipids. Expression of miR-33a/b was markedly increased in human carotid atherosclerotic plaques compared with normal arteries, and there was a concomitant decrease in mitochondrial regulatory genes PGC-1α, SLC25A25, NRF1, and TFAM, suggesting these genes are associated with advanced atherosclerosis in humans.

Conclusions:

This study demonstrates that anti-miR33 therapy derepresses genes that enhance mitochondrial respiration and ATP production, which in conjunction with increased ABCA1 expression, works to promote macrophage cholesterol efflux and reduce atherosclerosis.
Air Versus Oxygen in ST-Segment–Elevation Myocardial Infarction
Authors: Stub Dion , Smith Karen , Bernard Stephen , Nehme Ziad , Stephenson Michael , Bray Janet E. , Cameron Peter , Barger Bill , Ellims Andris H. , Taylor Andrew J. , Meredith Ian T. , Kaye David M.
Published: May 2015

Background—

Oxygen is commonly administered to patients with ST-elevation–myocardial infarction despite previous studies suggesting a possible increase in myocardial injury as a result of coronary vasoconstriction and heightened oxidative stress.

Methods and Results—

We conducted a multicenter, prospective, randomized, controlled trial comparing oxygen (8 L/min) with no supplemental oxygen in patients with ST-elevation–myocardial infarction diagnosed on paramedic 12-lead ECG. Of 638 patients randomized, 441 patients had confirmed ST-elevation–myocardial infarction and underwent primary end-point analysis. The primary end point was myocardial infarct size as assessed by cardiac enzymes, troponin I, and creatine kinase. Secondary end points included recurrent myocardial infarction, cardiac arrhythmia, and myocardial infarct size assessed by cardiac magnetic resonance imaging at 6 months. Mean peak troponin was similar in the oxygen and no oxygen groups (57.4 versus 48.0 μg/L; ratio, 1.20; 95% confidence interval, 0.92–1.56;
P
=0.18). There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group (1948 versus 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04–1.52;
P
=0.01). There was an increase in the rate of recurrent myocardial infarction in the oxygen group compared with the no oxygen group (5.5% versus 0.9%;
P
=0.006) and an increase in frequency of cardiac arrhythmia (40.4% versus 31.4%;
P
=0.05). At 6 months, the oxygen group had an increase in myocardial infarct size on cardiac magnetic resonance (n=139; 20.3 versus 13.1 g;
P
=0.04).

Conclusion—

Supplemental oxygen therapy in patients with ST-elevation–myocardial infarction but without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at 6 months.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01272713.
Finding Balance via Positive Psychological Assessment and Conceptualization
Authors: Owens Rhea L. , Magyar-Moe Jeana L. , Lopez Shane J.
Published: May 2015

This article provides an integrated review of positive psychological assessment and conceptualization methods and tools currently available to practitioners within the framework of a new assessment model—the Comprehensive Model of Positive Psychological Assessment. Cultural considerations stemming from the Culturally Appropriate Assessment Model were incorporated into the Practice Model of Positive Psychological Assessment to provide a comprehensive positive psychological assessment model. Furthermore, practice recommendations grounded in the positive psychological literature are provided to enhance the implementation of this model at various assessment stages. In addition, specific tools are provided to fill the gaps within the literature and guide clinicians in the formulation of a balanced assessment and conceptualization, including the Comprehensive Model of Positive Psychological Assessment Intake–Adult and Child/Adolescent Forms, the Comprehensive Model of Positive Psychological Assessment Semistructured Clinical Interview, the Comprehensive Model of Positive Psychological Assessment Report Template, and a new diagnostic approach—the Balanced Diagnostic Impressions (DICE-PM) Model.
Mind the Gap
Authors: Madison Heather , Pereira Anna , Korshøj Mette , Taylor Laura , Barr Alan , Rempel David
Published: May 2015

Objective:

The aim of this study was to evaluate the effects of key gap (distance between edges of keys) on computer keyboards on typing speed, percentage error, preference, and usability.

Background:

In Parts 1 and 2 of this series, a small key pitch (center-to-center distance between keys) was found to reduce productivity and usability, but the findings were confounded by gap. In this study, key gap was varied while holding key pitch constant.

Method:

Participants ( N = 25) typed on six keyboards, which differed in gap between keys (1, 3, or 5 mm) and pitch (16 or 17 mm; distance between centers of keys), while typing speed, accuracy, usability, and preference were measured.

Results:

There was no statistical interaction between gap and pitch. Accuracy was better for keyboards with a gap of 5 mm compared to a 1-mm gap ( p = .04). Net typing speed ( p = .02), accuracy ( p = .002), and most usability measures were better for keyboards with a pitch of 17 mm compared to a 16-mm pitch.

Conclusions:

The study findings support keyboard designs with a gap between keys of 5 mm over 1 mm and a key pitch of 17 mm over 16 mm.

Applications:

These findings may influence keyboard standards and design, especially the design of small keyboards used with portable devices, such as tablets and laptops.
Linking Health System Responsiveness to Political Rights and Civil Liberties
Authors: Witvliet Margot I. , Stronks Karien , Kunst Anton E. , Mahapatra Tanmay , Arah Onyebuchi A.
Published: May 2015

Responsiveness is a dimension of health system functioning and might be dependent upon contextual factors related to politics. Given this, we performed cross-national comparisons with the aim of investigating: 1) the associations of political factors with patients’ reports of health system responsiveness and 2) the extent to which health input and output might explain these associations. World Health Survey data were analyzed for 44 countries (n = 103 541). Main outcomes included, respectively, 8 and 7 responsiveness domains for inpatient and outpatient care. Linear multilevel regressions were used to assess the associations of politics (namely, civil liberties and political rights), socioeconomic development, health system input, and health system output (measured by maternal mortality) with responsiveness domains, adjusted for demographic factors. Political rights showed positive associations with dignity (regression coefficient = 0.086 [standard error = 0.039]), quality (0.092 [0.049]), and support (0.113 [0.048]) for inpatient care and with dignity (0.075 [0.040]), confidentiality (0.089 [0.043]), and quality (0.124 [0.053]) for outpatient care. Positive associations were observed for civil liberties as well. Health system input and output reduced observed associations. Results tentatively suggest that strengthening political rights and, to a certain extent, civil liberties might improve health system responsiveness, in part through their effect on health system input and output.
Effects of the 3D sizing of polyacrylonitrile fabric with carbon nanotube–SP1 protein complex on the interfacial properties of polyacrylonitrile/phenolic composites
Authors: Abramovitch Ido , Hoter Nerya , Levy Hagit , Gedanken Aharon , Wolf Amnon , Eitan Asa , Fine Tamir , Elmaleh Lea , Shalev Itzhak , Cohen Galit , Grimberg Elena , Nevo Yuval , Shoseyov Oded
Published: May 2015

Polyacrylonitrile–phenolic composites display excellent in-plane properties but perform poorly when out-of-plane, through-thickness properties are considered. Composite architectures with carbon nanotubes, either dispersed within the matrix or bound to a fabric, in traditional composites have the potential to alleviate this weakness. However, effective reinforcement of composites using carbon nanotubes is difficult, due to poor dispersion and interfacial stress transfer and has thus far been met with limited success and at high costs. This paper describes an innovative and cost-effective technology to improve these inferior mechanical properties by using an exceptionally stable protein, SP1, for CNT attachment to PAN fabric, forming a three-dimensional nano-reinforced structure. This work confirms remarkable improvements in interlaminar shear strength and through-thickness tensile strength of SP1/CNT-reinforced polyacrylonitrile composites.
Characterization of a hybrid Al2O3–aluminum matrix composite manufactured via composite extrusion
Authors: Reeb A , Walter V , Schulze V , Weidenmann KA
Published: May 2015

The development of new metal matrix composites for lightweight applications is aiming for an increase in specific strength and stiffness compared to conventional light metal alloys. The composite extrusion process is a promising manufacturing method for continuously reinforced light metal profiles. Especially the reinforcement with ceramic fibers leads to an increase in the specific strength and stiffness. For these investigations a hybrid composite is produced by using an Al2O3-fiber/AlMg0.6 composite wire which is embedded in an EN AW-6082 aluminum matrix. It is shown that the mechanical properties of the composite exceed those of the unreinforced matrix material. An explicit investigation of the deformation and damage behavior of this composite is given by optical strain analysis and in situ tensile tests in an X-ray micro computed tomograph (µ-CT). It was observed that during tensile loading multiple fracture of the composite wire occurs while exceeding the strain limit of the non-embedded composite wire. It could be shown that fracture of the composite wire is accompanied by strain localization and therefore strain hardening occurs in vicinity of the internal fracture, which leads to multiple necking of the specimen. The µ-CT analysis reveals the intrinsic damage mechanisms and shows the beginning of ceramic fiber fracture which showed evidence for a local load distribution between the fibers resulting in a planar fracture of the composite wire. The multiple fracture of the wire allows for an interface shear strength analysis and indicates a good bonding of the composite wire.
Effects of Material Properties on Bacterial Adhesion and Biofilm Formation
Authors: Song F. , Koo H. , Ren D.
Published: May 2015

Adhesion of microbes, such as bacteria and fungi, to surfaces and the subsequent formation of biofilms cause multidrug-tolerant infections in humans and fouling of medical devices. To address these challenges, it is important to understand how material properties affect microbe-surface interactions and engineer better nonfouling materials. Here we review the recent progresses in this field and discuss the main challenges and opportunities. In particular, we focus on bacterial biofilms and review the effects of surface energy, charge, topography, and stiffness of substratum material on bacterial adhesion. We summarize how these surface properties influence oral biofilm formation, and we discuss the important findings from nondental systems that have potential applications in dental medicine.
A Large National Cohort Study of the Association between Bisphosphonates and Osteonecrosis of the Jaw in Patients with Osteoporosis
Authors: Kwon J.-W. , Park E.-J. , Jung S.-Y. , Sohn H.S. , Ryu H. , Suh H.S.
Published: May 2015

The purpose of this study was to examine the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis. A nested case-control study was performed using the claims database during 2002 to 2010 provided by the National Health Insurance Service. We identified a cohort of individuals with diagnosis of osteoporosis during 2002 to 2010. Cases and controls were identified during 2004 to 2010, and the date of potential cases of ONJ was defined as the index date. Bisphosphonate exposure was evaluated during 2 y prior to the index date. The association between bisphosphonate exposure and ONJ was tested by performing a conditional logistic regression analysis for matched data, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Subjects were classified as nonuser, recent user, past user, or continuous user, depending on the prescription of bisphosphonates in 2 periods (1 to 2 y and 0 to 1 y prior to the index date). Continuous users were defined as patients who were exposed to bisphosphonate in both periods. We also examined the impact of bisphosphonate medication compliance by measuring the cumulative duration of exposure (CDE) on the risk of ONJ. A total of 212 cases with ONJ and 2,120 controls matched by sex, age, income level, and insurance type were identified among 109,787 patients with osteoporosis out of 1,025,340 enrollees in the sample cohort. The odds of having ONJ after adjusting for patient comorbidities significantly increased in continuous users of bisphosphonates (OR, 3.9; 95% CI, 2.4 to 6.2) compared to nonusers. Increased odds of ONJ were observed as CDE increased. The adjusted OR in patients with 1.5 y < CDE ≤ 2 y prior to the index date was 7.8 (95% CI, 4.0 to 15.5) versus nonusers. Our study results support significantly increased occurrences of potential ONJ in patients with osteoporosis who were exposed to bisphosphonates compared to those without exposure.
A Major Fimbrilin Variant of Mfa1 Fimbriae in Porphyromonas gingivalis
Authors: Nagano K. , Hasegawa Y. , Yoshida Y. , Yoshimura F.
Published: May 2015

The periodontal pathogen Porphyromonas gingivalis is known to express 2 distinct types of fimbriae: FimA and Mfa1 fimbriae. However, we previously reported that fimbria-like structures were found in a P. gingivalis strain in which neither FimA nor Mfa1 fimbriae were detected. In this study, we identified a major protein in the bacterial lysates of the strain, which has been reported as the 53-kDa major outer membrane protein of P. gingivalis (53K protein) and subsequently reported as a major fimbrilin of a novel-type fimbria. Sequencing of the chromosomal DNA of the strain showed that the 53k gene (encoding the 53K protein) was located at a locus corresponding to the mfa1 gene (encoding the Mfa1 protein, which is a major fimbrilin of Mfa1 fimbriae) of the ATCC 33277 type strain. However, the 53K and Mfa1 proteins showed a low amino acid sequence homology and different antigenicity. The 53K protein was detected in 34 of 84 (41%) P. gingivalis strains, while the Mfa1 protein was detected in 44% of the strains. No strain expressed both 53K and Mfa1 proteins. Additionally, fimbriae were normally expressed in mutants in which the 53k and mfa1 genes were interchanged. These results indicate that the 53K protein is another major fimbrilin of Mfa1 fimbriae in P. gingivalis.
Broken Windows, Neighborhoods, and the Legitimacy of Law Enforcement or Why I Fell in and out of Love with Zimbardo
Authors: Meares Tracey
Published: May 2015

Objective:

Wilson and Kelling (1982) introduced Zimbardo’s “broken windows” into the lexicon a little over 30 years ago. This article explores broken windows from a legal policy perspective, with the aim of putting forth a framework for integrating what we know (or think we know) about the potential effects of broken windows policing into our goals for improving high-crime neighborhoods.

Methods:

A narrative review was carried out of key social science research on the broken windows perspective.

Results:

The first part of the article explains the appeal of broken windows to legal theorists interested in challenging criminal law policy based on a law and economics approach. The second part reviews maturing broken windows research and evaluations of broken windows policing. The third part explains the contours of an analysis that addresses the value of broken windows policing from a legal policy perspective.

Conclusion:

While I remain a tentative fan of broken windows policing, I argue that the modest outcomes of broken windows policing do not justify the problems these policies create from a procedural justice context. The policy literature ignores this trade-off, and a curriculum framework that emphasizes how the criminal justice system educates citizens may offer a promising alternative.