bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression profiles of alveolar type II cells of chronic obstructive pulmonary disease: a case–control study
Authors: Fujino Naoya , Ota Chiharu , Takahashi Toru , Suzuki Takaya , Suzuki Satoshi , Yamada Mitsuhiro , Nagatomi Ryouichi , Kondo Takashi , Yamaya Mutsuo , Kubo Hiroshi
Published: November 2012

Objectives

The aim of this study was to identify the gene expression pattern specific in alveolar epithelial type II cells (ATII cells) isolated from patients with chronic obstructive pulmonary disease (COPD).

Design

Case control.

Setting

Two hospitals in Japan.

Participants

Three patients without COPD and three patients with COPD in microarray analyses. Five smokers without COPD and nine smokers with COPD in the following analyses.

Primary and secondary outcome measured

Primary outcome included identification of differentially expressed genes and activated or inhibited pathways in ATII cells of the patients with COPD, compared to those of the patients without COPD, using Affymetrix gene expression arrays. Secondary outcome included validation of the results of microarray analyses by quantitative reverse transcription-PCR.

Results

We isolated ATII cells from COPD and non-COPD lungs using fluorescence-activated cell sorting. We performed Affymetrix gene expression arrays on both types of ATII cells. Gene set enrichment analyses revealed that two major gene sets were enriched in ATII cells from COPD lungs: interferon-responsive gene sets and gene sets associated with cell cycle progression. Gene ontology term enrichment analyses indicated that among the interferon-stimulated genes, ATII cells in COPD expressed genes such asPSMB8,PSMB9,TAP1andTAP2associated with the antigen processing and presentation pathway. We validated the results of the microarray analyses using quantitative reverse transcriptase-PCR. In addition, FACS analysis indicated that the percentage of ATII cells to CD45-negative lung cells isolated from COPD lungs were significantly increased more than that from non-COPD lungs.

Conclusions

Our study demonstrated that interferon-stimulated genes involved in the antigen processing and presentation pathway and genes involved in cell cycle progression were enriched in ATII cells of the patients with COPD. These pathways might alter phenotypes of ATII cells in COPD lungs.
Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study
Authors: Lambert Stephen Bernard , Ware Robert S , Cook Anne L , Maguire Frances A , Whiley David M , Bialasiewicz Seweryn , Mackay Ian M , Wang David , Sloots Theo P , Nissen Michael D , Grimwood Keith
Published: November 2012

Introduction

Even in developed economies infectious diseases remain the most common cause of illness in early childhood. Our current understanding of the epidemiology of these infections is limited by reliance on data from decades ago performed using low-sensitivity laboratory methods, and recent studies reporting severe, hospital-managed disease.

Methods and analysis

The Observational Research in Childhood Infectious Diseases (ORChID) study is an ongoing study enrolling a dynamic birth cohort to document the community-based epidemiology of viral respiratory and gastrointestinal infections in early childhood. Women are recruited antenatally, and their healthy newborn is followed for the first 2 years of life. Parents keep a daily symptom diary for the study child, collect a weekly anterior nose swab and dirty nappy swab and complete a burden diary when a child meets pre-defined illness criteria. Specimens will be tested for a wide range of viruses by real-time PCR assays. Primary analyses involves calculating incidence rates for acute respiratory illness (ARI) and acute gastroenteritis (AGE) for the cohort by age and seasonality. Control material from children when they are without symptoms will allow us to determine what proportion of ARIs and AGE can be attributed to specific pathogens. Secondary analyses will assess the incidence and shedding duration of specific respiratory and gastrointestinal pathogens.

Ethics and dissemination

This study is approved by The Human Research Ethics Committees of the Children's Health Queensland Hospital and Health Service, the Royal Brisbane and Women's Hospital and The University of Queensland.

Trial registration

clinicaltrials.govNCT01304914.
Epidemiological survey of the hoof wall cavity (‘Gidoh’ in Japanese) in racehorses
Authors: Kuwano A. , Yamauchi Y. , Sasagawa T. , Sasaki N. , Hamano H.
Published: November 2012

In October 2001, a survey was conducted about cavities formed within the hoof wall (called GIDOH in Japanese) of racehorses at the Ritto and Miho Training Centres, which are managed by the Japan Racing Association (JRA). Gidoh is defined as a progressive cavity within the deep layers between the stratum medium and stratum internum. A total of 148 out of 5386 surveyed horses (2.75 per cent) were affected. Out of 244 affected feet, fore hooves (84.02 per cent) were more susceptible than hind hooves, and the site most affected was midline dead centre of the toe (59.62 per cent) which tends to place extra stress at the break‐over point in a straight‐line exercise. Logistic regression analysis revealed that prevalence was significantly related with horse affiliation (OR 0.65, 95 per cent CI 0.46 to 0.91) and age (OR 1.43 per one year, 95 per cent CI 1.27 to 1.61). We hypothesised that the primary cause of Gidoh development in JRA stables was mechanical deformation of the hoof wall during exercise, and secondary exciting causes can subsequently lead to the spread of the lesion over the entire hoof wall.
Influences on antimicrobial prescribing behaviour of veterinary practitioners in cattle practice in Ireland
Authors: Gibbons J. F. , Boland F. , Buckley J. F. , Butler F. , Egan J. , Fanning S. , Markey B. K. , Leonard F. C.
Published: November 2012

Guidelines on prudent antimicrobial use in veterinary medicine have been developed to reduce inappropriate prescribing of antimicrobials. Such guidelines focus mainly on the clinical and pharmacological indications for prescribing. A questionnaire study of veterinary surgeons engaged in cattle practice was completed to determine if non‐clinical issues influence the decision to prescribe antimicrobials, and to assess if pharmacological and non‐pharmacological issues influence the choice of antimicrobial prescribed. Non‐clinical issues, including issues related to professional stress, influenced the prescribing decision of the majority of respondents. However, the nature of the veterinarian–client relationship did not influence the prescribing behaviour of the majority of respondents. Pharmacological and non‐pharmacological issues influenced the choice of antimicrobial prescribed. The veterinary surgeon's prior experience of a drug was considered ‘often’ or ‘always’ by 95.7 per cent of respondents when making this decision. The findings of this study have implications for the recognition and management of stress within the profession, and for the development of intervention strategies to reduce inappropriate antimicrobial prescribing.
A MULTI-LAYER NEURAL-MASS MODEL FOR LEARNING SEQUENCES USING THETA/GAMMA OSCILLATIONS
Authors: CONA FILIPPO , URSINO MAURO
Published: November 2012

A neural mass model for the memorization of sequences is presented. It exploits three layers of cortical columns that generate a theta/gamma rhythm. The first layer implements an auto-associative memory working in the theta range; the second segments objects in the gamma range; finally, the feedback interactions between the third and the second layers realize a hetero-associative memory for learning a sequence. After training with Hebbian and anti-Hebbian rules, the network recovers sequences and accounts for the phase-precession phenomenon.
FAY'S MATRIX IDENTITY FOR VECTOR BUNDLES ON A CURVE
Authors: RAINA A. K.
Published: November 2012

Among the less well-known identities established by Fay is a matrix identity which can be regarded as a vector bundle generalization of his better known trisecant identity. We show how our earlier proof of the latter can be adapted to prove his matrix identity.
ENHANCEMENT OF CHARGED HIGGS PRODUCTION IN ASSOCIATION WITH W± AT MUON COLLIDERS IN GENERAL TWO HIGGS DOUBLET MODELS
Authors: HASHEMI M.
Published: November 2012

The charged Higgs production associated with a W± boson has a smooth cross-section as a function of the charged Higgs mass at muon colliders. The cross-section in minimal supersymmetric standard model (MSSM) is about 25 fb in the range 200 GeV < mH± <400 GeV with tan β = 50. This is much larger than the corresponding cross-section at an e+e- collider which reaches a fraction of femtobarn. The observability of this charged Higgs production at a muon collider has been recently studied in an earlier work leading to the result that with 1 ab-1, a 5σ signal can be observed throughout the aforementioned mass range. In this paper, results of a study based on a general two Higgs doublet model (types II and III) are presented and the cross-section of the charged Higgs production in the most sensitive parameter space is evaluated. It is concluded that the cross-section increases with increasing neutral Higgs boson masses involved in the s-channel diagram and can be as large as several picobarn with tan β = 50. The region of "physical Higgs boson mass" parameter space which could lead to a 5σ signal at 50 fb-1 is specified.
STUDY OF ORGANIC THIN FILM TRANSISTOR WITH PHOTOPATTERNED GATE DIELECTRIC
Authors: XU HONGGUANG , RAN FENG , JI YUAN , ZHANG JIMEI , ZHU WENQING
Published: November 2012

In order to investigate the feasibility of gating organic field-effect transistors (OFETs) using a photosensitive photoresist material, pentacene-based OFETs were fabricated on indium tin oxide (ITO) glass. The gate dielectric was found to be easily patterned by spin coating and UV exposure, and has an excellent surface roughness of 0.22 nm and good insulating properties, resulting in a low leakage current (49 nA at 2 MV/cm) at a dielectric thickness of 290 nm. The OFET with photopatterned gate dielectric exhibited good electric characteristics, including a high field-effect mobility of 0.15 cm2/Vs, a threshold voltage of -9.9 V, and on/off current ratio of ~104. The high matching of surface free energy between the gate dielectric and pentacene is proved to be contributed to the good performance of the device.
A NEW RESONANT COUPLING BETWEEN AN ANALYTE-FILLED CORE MODE AND A SUPERMODE OF A MULTI-CORE HOLEY FIBER BASED PLASMONIC SENSOR
Authors: POPESCU V. A.
Published: November 2012

A new resonant coupling between an analyte-filled core mode and a supermode in a multi-core holey fiber recently designed for sensing of benzene is investigated using a finite element method. The dominant electric field of the fundamental core supermode is in a high degree extended at this resonance from the hexagonal solid cores to the analyte (benzene) layer and vice versa for the analyte-filled fundamental core mode. The full width at half maximum (FWHM) bandwidth for the fundamental supermode is 5.3 nm. When the analyte refractive index is increased by 0.001 RIU, the phase matching point is shifted by 4.5 nm toward longer wavelengths, with a corresponding sensitivity better than 2.2 × 10-5 RIU and a very high value of the signal-to-noise ratio (0.85). The resonance of a fundamental supermode with the first order of surface plasmon resonance mode in the infrared region (λ = 1.33825 μ m ) can be used together with a resonant coupling between a fundamental supermode with an analyte fundamental mode in visible (λ = 0.6415 μ m ) part of the spectrum for increasing the performance of the sensor.
QUANTUM THREE-QUBIT W-STATE SHARING VIA POSITIVE OPERATOR-VALUED MEASUREMENT AND PROJECTIVE MEASUREMENT
Authors: BAI MING-QIANG , MO ZHI-WEN
Published: November 2012

In this paper, by using a proper positive operator-valued measurement, we propose a new tripartite scheme for probabilistically implementing quantum state sharing of an arbitrary unknown three-qubit state with two non-maximally entangled states, one is four-qubit state, another is three-qubit state. In the scheme, the Boss Alice partitions her unknown original state with two Bell-state measurements and a single-qubit projective measurement. Then she publishes her measurement results via a classical channel. With an agent Charlie's help, another agent Bob can recover the original state in probabilistic manner by performing a proper POVM.
ELECTRICAL TRANSPORT THROUGH MICRO POROUS TRACK ETCH MEMBRANES OF SAME POROSITY
Authors: GARG RAVISH , KUMAR VIJAY , KUMAR DINESH , CHAKARVARTI S. K.
Published: November 2012

Porosity, pore size and thickness of membrane are vital factors to influence the transport phenomena through micro porous track etch membranes (TEMs) and affect the various applications like separations, drug release, flow control, bio-sensing and cell size detection etc. based on transport process. Therefore, a better understanding of transport mechanism through TEMs is required for new applications in various thrust areas like biomedical devices and packaging of foods and drugs. Transport studies of electrolytic solutions of potassium chloride, through porous polycarbonate TEMS having cylindrical pores of size 0.2 μm and 0.4 μm with same porosity of 15%, have been carried out using an electrochemical cell. In this technique, the etched filter is sandwiched between two compartments of cell in such a way that the TEM acts as a membrane separating the cell into two chambers. The two chambers are then filled with electrolyte solution ( KCl in distilled water). The current voltage characteristics have been drawn by stepping the voltage ranging 0 to 10 V using Keithley 2400 Series Source Measurement Unit. The results indicate that rate of ion transport through cylindrical pores although is independent of pore size of TEMs of same porosity but there seems to be effect of TEM aperture size exposed to the electrolyte used in conducting cell on ion transport magnitude. From the experimental studies, a large deviation in the conduction through TEMs was observed when compared with theoretical consideration which led to the need for modification in the applicability of simple Ohm's law to the conduction through TEMs. It is found that ion transport increases with increase in area of aperture of TEM but much lower than the expected theoretically value.
ON THE THOMPSON'S CONJECTURE ON CONJUGACY CLASSES SIZES
Authors: AHANJIDEH NEDA
Published: November 2012

In this paper, we prove a conjecture of Thompson for an infinite class of simple groups of Lie type. In fact, we show that every finite group G with the property Φ(G) ∩ Z(G) = 1 and N(G) = N(Dn(q)) is isomorphic to Z(G) × Dn(q), where n ≥ 5 and n ≠ 8. Note that N(G), Φ(G) and Z(G) are the set of lengths of conjugacy classes of G, Frattini subgroup of G and the center of G, respectively.
ON FINITE GENERATION OF SELF-SIMILAR GROUPS OF FINITE TYPE
Authors: BONDARENKO IEVGEN V. , SAMOILOVYCH IGOR O.
Published: November 2012

A self-similar group of finite type is the profinite group of all automorphisms of a regular rooted tree that locally around every vertex act as elements of a given finite group of allowed actions. We provide criteria for determining when a self-similar group of finite type is finite, level-transitive, or topologically finitely generated. Using these criteria and GAP computations we show that for the binary alphabet there is no infinite topologically finitely generated self-similar group given by patterns of depth 3, and there are 32 such groups for depth 4.
AUTOMATIC DETECTION OF SIMILARITIES AND DIFFERENCES BETWEEN SMALL BOWEL POLYPS AND ULCERS WITH A DATA MINING APPROACH IN WIRELESS CAPSULE ENDOSCOPY VIDEOS
Authors: KARARGYRIS A. , POUAGARE M. , KARARGYRIS O. , BOURBAKIS N.
Published: November 2012

Over the past decade Wireless Capsule Endoscopy (WCE) technology has become a very useful tool for diagnosing diseases within the human digestive tract. Using WCE physicians can examine the digestive tract in a minimum invasive way searching for pathological abnormalities such as bleeding, polyps, ulcers and Crohn's disease. In order for WCE to be more effective for gastroenterologists, engineers have developed software methods to automatically detect these diseases at high successful rate. Using proposed a synergistic methodology for automatic discovering polyps (protrusions) and ulcers in WCE video frames, a data mining approach is used that offers useful information about ulcers, polyps and normal tissues and their visual similarities. Finally, results of the methodology are given and statistical comparisons are also presented relevant to other works.
INFLUENCE OF THE ELECTRODEPOSITION POTENTIAL ON THE Co-Cu ALLOYS THIN FILMS PROPERTIES
Authors: MENTAR L. , KHELLADI M. R. , BENIAICHE A. , AZIZI A.
Published: November 2012

Co-Cu alloy thin films were electrodeposited on a fluorine-doped tin oxide (FTO)-coated conducting glass substrate from a sulfate solution at applied potentials ranging from -0.7 V to -1.3 V versus saturated calomel electrode (SCE). Voltammetric studies showed that the composition and, consequently, the potential dissolution of Co depend greatly on the applied potentials. The compositional measurement, which was made using an atomic absorption spectroscopy (AAS), demonstrated that the Co content of the films considerably increases as the applied potentials to tend toward negative values. The SEM study showed that a granular structure of the electrodeposited Co-Cu . X-ray diffraction measurements showed that all peaks of the Co-Cu films were consistent with those of a typical Co hcp and Co -fcc mixed phase and Cu -fcc phase at low potential. The increase of the applied potential induces a decrease in the grain size and the lattice constant. The magnetic hysteresis measurements carried out by an alternating gradient force magnetometer (AGFM) revealed the existence of a ferromagnetic behavior with an in-plane easy magnetization axis for the film deposited at -1.1 V versus SCE. However, for applied potentials of -1.2 V and -1.3 V, we observe the coexistence of a dominant in-plane easy magnetization along with a perpendicular one.
CARBON-DOPEDTiO2NANOTUBES: EXPERIMENTAL AND COMPUTATIONAL STUDIES
Authors: HUANG WEN-FEI , WU PIN-JIUN , HSU WEI-CHIH , WU CHIH-WEI , LIANG K. S. , LIN M. C.
Published: November 2012

C-doped TiO2nanotubes (NTs) with anatase structure, prepared by anodizing the polished Ti foils, were characterized using X-ray diffraction (XRD), field-emission scanning electron microscope (FE-SEM), and synchrotron-based X-ray photoemission spectroscopy (XPS). XPS results show electron losses in C atoms, no electron change in Ti atoms, and two doping energy levels appeared in band gaps. Structural geometries, DOSs, PDOSs, and Bader charge analyses of C -doped TiO2anatase are predicted by periodic DFT calculations. Eight doping positions were taken into consideration: two substitutional cases (in oxygen and titanium sites) and six interstitial cases. We found that the interstitial carbon doping type is the most stable one, whereas the substitutional cases are rather unstable. Band-gap modifications can also be found in oxygen substitution, but not in titanium substitution. Both band-gap modification and non-band-gap modification are found in the interstitial carbon doping. In these eight C -doping systems, only the C atom in the oxygen substitution case gains electrons, 1.14 e, and others present electron losses within 0.5–4.00 e. The results of XPS measurements, DOSs calculations, and Bader charge analyses show that carbon interstitial is the most likely doping type for the C -doped TiO2NTs.
SEIBERG–WITTEN EQUATIONS ON 8-DIMENSIONAL MANIFOLDS WITH SU(4)-STRUCTURE
Authors: KARAPAZAR ŞENAY
Published: November 2012

Seiberg–Witten equations on 8-manifolds with Spin(7)-holonomy are introduced in [A. H. Bilge, T. Dereli and S. Koçak, Monopole equations on 8-manifolds with Spin(7) holonomy, Commun. Math. Phys.203(1) (1999) 21–30] and it is given a local solution for these equations. In this work, we write down similar Seiberg–Witten equations on 8-dimensional manifolds with SU(4)-structure and give a global solution for these equations.
0 + 1-DIMENSIONAL TQFT: FROM HILBERT VECTOR SPACE TO TANGLE CATEGORY
Authors: SHI XU-GUANG
Published: November 2012

In general, topological quantum field theory (TQFT) is studied in detail from the n-dimensional cobordism (nCob) to the Hilbert vector space. However, we study the TQFT in the different way in this paper, that is, the TQFT is studied from the Hilbert vector space to nCob. To do this, the theory called the ϕ-mapping topological current theory is used. The relation between the objects and zero points of the Hilbert states in the Hilbert vector space is studied in this frame. The relation between the morphism and topological current is revealed too.
IMPROVING HAMILTONIAN ENERGY EQUATIONS ON THE KÄHLER JET BUNDLES
Authors: CIVELEK SEVKET , AYCAN CANSEL , DAGLI SIMGE
Published: November 2012

The aim of this paper is to improve Hamiltonian energy equations for the complex jet bundles using Kähler manifolds. The coordinates on the bundle structure of Kähler manifolds have been given for real and imaginary dimensions. For given bundle structures, all fundamental geometrical properties have been investigated in Hamiltonian energy equations and applications to complex bundle structures. The improved Hamiltonian energy equations have been applied to the presented example in order to test its performance. Moreover, we have presented a new concept of velocity and time dimensions for energy movement equations. Results showed that imaginary Hamiltonian values are opposed to real Hamiltonian values in 2n dimensions. Finally, this study showed a physical application and interpretation of velocity and time dimensions in Hamiltonian energy equations for given examples.
EXISTENCE AND UNIQUENESS FOR SOLUTION OF RICCI FLOW ON FINSLER MANIFOLDS
Authors: AZAMI SHAHROUD , RAZAVI ASADOLLAH
Published: November 2012

This paper shows that the Ricci flow on Finsler manifolds with Berwald metrics cannot possibly be strictly parabolic. Then, we will define a modified flow which is strictly parabolic and by using it, we will prove the existence and uniqueness for solution of Ricci flow on Finsler manifolds.
STOCHASTIC DISCRETE-TIME AGE-OF-INFECTION EPIDEMIC MODELS
Authors: KATRIEL GUY
Published: November 2012

We present an epidemic model which can incorporate essential biological detail as well as the intrinsic demographic stochasticity of the epidemic process, yet is very simple, enabling rapid generation of a large number of simulations. A deterministic version of the model is also derived, in the limit of infinitely large populations, and a final-size formula for the deterministic model is proved. A key advantage of the model proposed is that it is possible to write down an explicit likelihood functions for it, which enables a systematic procedure for fitting parameters to real incidence data, using maximum likelihood.
MONODISPERSED SILICA NANOSPHERES ENCAPSULATING Fe3O4 AND LaF3:Eu3+ NANOPARTICLES FOR MRI CONTRAST AGENT AND LUMINESCENT IMAGING
Authors: TIAN YANG , YU BINBIN , YANG HONG-YU , LIAO JI
Published: November 2012

Bifunctional nanospheres of silica encapsulating Fe3O4 and LaF3 : Eu nanoparticles were synthesized in a reverse microemulsion solution. The nanospheres were perfectly monodispersed with a small diameter of 20 nm. The composition of the bifunctional nanospheres was confirmed by powder X-ray diffraction. Their magnetic and luminescent properties were measured at room temperature. The relaxation efficiency and T2-weighted images showed the high-performance for the product as a resonance imaging contrast agent. In addition, a qualitative cell uptake in human cervical cancer HeLa cells demonstrated that the SFLE nanospheres were efficiently up-taken into cytosol. Taken together, these findings suggest that the SiO2 / Fe3O4 - LaF3 : Eu 3+ nanospheres are good luminescence probes for bio-imaging.
SINGLE-PHASE HEAT TRANSFER AND PRESSURE DROP INSIDE INTERNALLY HELICAL-GROOVED HORIZONTAL SMALL-DIAMETER TUBES
Authors: INOUE NORIHIRO , ICHINOSE JUNYA
Published: November 2012

An experimental study on pressure drop and heat transfer in single-phase was carried out using 10 types of internally helical-grooved and smooth small-diameter tubes with an outside diameter of 4 mm. The results are listed below: (1) In the turbulent flow region, fin height had the greatest effect, helix angle had only a minor effect, and the number of grooves had almost no effect upon the pressure drop versus the mass flow rate of the 4-mm grooved small-diameter tubes. In the laminar flow region, except for fin height, the shapes of the internal grooves had scarcely any effect upon pressure drop. (2) In the turbulent flow region, the heat transfer coefficients of the 4-mm grooved small-diameter tubes were greatly affected by fin height. The heat transfer coefficients became the maximum when a helix angle was near 15°, and there is a different tendency in the experiments of the pressure drop. On the other hand, there is almost no effect of the number of grooves. In the laminar flow region, there were no large differences in the heat transfer coefficients between the internally helical-grooved tubes and smooth small-diameter tube. (3) New empirical correlations for the friction factor and heat transfer coefficient in the laminar and turbulent flow regions were developed based on the experimental values. (4) The performance assessment in consideration of both heat transfer and pressure drop was indicated by using Colburn's analogy.
Perturbative Expansion of FBSDE in an Incomplete Market with Stochastic Volatility
Authors: Fujii Masaaki , Takahashi Akihiko
Published: November 2012

In this work, we apply our newly proposed perturbative expansion technique to a quadratic growth FBSDE appearing in an incomplete market with stochastic volatility that is not perfectly hedgeable. By combining standard asymptotic expansion technique for the underlying volatility process, we derive explicit expression for the solution of the FBSDE up to the third order of volatility-of-volatility for its level, and the fourth order for its diffusion part that can be directly translated into the optimal investment strategy. We compare our approximation with the exact solution, which is known to be derived by the Cole–Hopf transformation in this popular setup. The result is very encouraging and shows good accuracy of the approximation up to quite long maturities. Since our new methodology can be extended straightforwardly to multi-dimensional setups, we expect it will open real possibilities to obtain explicit optimal portfolios or hedging strategies under realistic assumptions.
Incremental emplacement of the sheeted Glas Bheinn Porphyritic Dolerite, Ardnamurchan, NW Scotland
Authors: Magee C.
Published: November 2012

Synopsis

The
c
. 58 Ma Ardnamurchan Central Complex represents the deeply eroded roots of an ancient volcanic edifice that purportedly formed during three discrete phases of igneous activity. Although only a relatively small component of the first phase of magmatism (Centre 1), the Glas Bheinn Porphyritic Dolerite provides important insights into igneous emplacement mechanisms and age relationships on Ardnamurchan. New field observations combined with anisotropy of magnetic susceptibility analyses, which allow primary magma flow patterns to be reconstructed, suggest that the Glas Bheinn Porphyritic Dolerite consists of numerous inclined sheet intrusions that, overall, have a flower intrusive structure. Vertically ascending sheets that do not appear to be related to the Centre 1 focus are proposed to have been deflected into the inclined sheets and sills by the load of the overlying volcanic edifice. Cross-cutting relationships further suggest that some sheets of the Glas Bheinn Porphyritic Dolerite are later than several Outer Centre 2 cone sheets. These observations suggest that the Glas Bheinn Porphyritic Dolerite cannot be attributed to Centre 1.

Supplementary material:

AMS block sample locations and magnetic data are available at
www.geolsoc.org.uk/SUP18562
A post-collision slab-breakoff model for the orgin of the Middle Eocene magmatic rocks of the Armutlu–Almacık belt, NW Turkey and its regional implications
Authors: Gülmez Fatma , Genç Ş. Can , Keskİn Mehmet , Tüysüz Okan
Published: November 2012

Middle Eocene magmatic rocks (MEMR) (49.3±2 to 38.1±1.9 Ma) formed an east–west trending belt after continental collision and rest unconformably on pre-Middle Eocene units as a common cover. The origin and tectonic setting of MEMR are controversial as both arc and post-collisional settings are proposed. We present new geological and petrological data from the western part of the belt, between the Armutlu Peninsula and the Almacık Mountains. The MEMR are represented by basic to intermediate volcanic rocks, dykes and coeval granites. The lavas exhibit a continuous trend from basalt to dacite. The MEMR as a whole display low- to medium-K subalkaline (to rarely mildly alkaline) affinities and a calc-alkaline trend. On N-type Mid Ocean Ridge Basalt-normalized spidergrams these rocks display relative enrichment in large ion lithophile elements, slight enrichment in light rare earth elements, but depletion in Ta and Nb. Geochemical data and Sr, Nd, Pb and δ
18
O isotope compositions, coupled with εNd
(T)
values, reveal that the MEMR magma was of hybrid type, with both depleted sub-continental lithospheric mantle and crustal components. We conclude that the MEMR was produced in a post-collisional setting, and we favour a slab-breakoff mechanism to explain this as it is consistent with the known Middle Eocene tectonic evolution of northwestern Turkey.
The Biology of Recent Thymic Emigrants
Authors: Fink Pamela J.
Published: November 2012

The generation of the TCRαβ lineage of T cells occurs in the thymus through a series of orchestrated developmental events that result in a carefully selected population of CD4 or CD8 lineage–committed TCR+thymocytes capable of recognizing foreign antigen in the context of self MHC. T cells first exit the thymus in a phenotypically and functionally immature state and require an approximately 3-week period of post-thymic maturation before transitioning into the mature T cell compartment. A greater understanding of recent thymic emigrant biology has come with the development of methods to exclusively identify and isolate this population for further characterization. I now review current knowledge about the phenotype and function of this key but understudied population of peripheral T cells.
Defective Complement Inhibitory Function Predisposes to Renal Disease
Authors: Java Anuja , Atkinson John , Salmon Jane
Published: November 2012

The role of the complement system in mediating human renal disease has long been recognized in immune-complex excess syndromes such as systemic lupus erythematosus and in dense deposit disease in which no immunoglobulin (Ig) is present. Over the past 15 years, mutations in complement regulatory genes have been demonstrated to predispose to thrombotic microangiopathies including atypical hemolytic uremic syndrome, C3 and C1q glomerulopathies, and preeclampsia. Excessive complement activation on an endothelial cell, due to either an autoantibody or a regulatory protein deficiency, sets up a procoagulant state in these diseases as well as in the antiphospholipid syndrome. Knowledge of the genes involved and the functional consequences of alterations in their structure has led to therapy that blocks complement activation.
Duty-Hour Limits and Patient Care and Resident Outcomes: Can High-Quality Studies Offer Insight into Complex Relationships?
Authors: Philibert Ingrid , Nasca Thomas , Brigham Timothy , Shapiro Jane
Published: November 2012

Long hours are an accepted component of resident education, yet data suggest they contribute to fatigue that may compromise patient safety. A systematic review confirms that limiting duty hours increases residents' hours of sleep and improves objective measures of alertness. Most studies of operative experience for surgical residents found no effect, and there is evidence of a limited positive effect on residents' mood. We find a mixed effect on patient safety, although problems with supervision, rather than the limits, may be responsible or contibute; evidence of reduced continuity of care and reduced continuity in residents' clinical education; and evidence that increased workload under the limits has a negative effect on patient and resident outcomes. We highlight specific areas for research and offer recommendations for national policy.
The Rotavirus Saga Revisited
Authors: Shaw Alan R.
Published: November 2012

Two live oral rotavirus vaccines were approved by the US Food and Drug Administration in 2005 and 2008, following large studies of ∼70,000 each in order to address questions about intussusception triggered by a third earlier vaccine. Both new rotavirus vaccines showed almost identical rates of intussusception in vaccine and placebo recipients. These vaccines have been used extensively in the United States with positive results. Efforts are under way to implement these vaccines in developing countries where the need is greatest.
Peripheral resistance: a link between global airflow obstruction and regional ventilation distribution
Authors: Wongviriyawong C. , Harris R. S. , Greenblatt E. , Winkler T. , Venegas J. G.
Published: November 2012

Airflow obstruction and heterogeneities in airway constriction and ventilation distribution are well-described prominent features of asthma. However, the mechanistic link between these global and regional features has not been well defined. We speculate that peripheral airway resistance ( Rp) may provide such a link. Structural and functional parameters are estimated from PET and HRCT images of asthmatic (AS) and nonasthmatic (NA) subjects measured at baseline (BASE) and post-methacholine challenge (POST). Conductances of 35 anatomically defined proximal airways are estimated from airway geometry obtained from high-resolution computed tomography (HRCT) images. Compliances of sublobar regions subtended by 19 most distal airways are estimated from changes in regional gas volume between two lung volumes. Specific ventilations (s V̇) of these sublobar regions are evaluated from 13NN-washout PET scans. For each pathway connecting the trachea to sublobar region, values of Rp required to explain the sV̇ distribution and global airflow obstruction are computed. Results show that Rp is highly heterogeneous within each subject, but has average values consistent with global values in the literature. The contribution of Rp to total pathway resistance ( RT) increased substantially for POST ( P < 0.0001). The fraction Rp /RT was higher in AS than NA at POST ( P < 0.0001) but similar at BASE (range: 0.960–0.997, median: 0.990). For POST, Rp /RT range was 0.979–0.999 (NA) and 0.981–0.995 (AS). This approach allows for estimations of peripheral airway resistance within anatomically defined sublobar regions in vivo human lungs and may be used to evaluate peripheral effects of therapy in a subject specific manner.
PNUTS Functions as a Proto-Oncogene by Sequestering PTEN
Authors: Kavela Sridhar , Shinde Swapnil R. , Ratheesh Raman , Viswakalyan Kotapalli , Bashyam Murali D. , Gowrishankar Swarnalata , Vamsy Mohana , Pattnaik Sujit , Rao Subramanyeshwar , Sastry Regulagadda A. , Srinivasulu Mukta , Chen Junjie , Maddika Subbareddy
Published: November 2012

PTEN is a well-defined tumor suppressor gene that antagonizes the PI3K/Akt pathway to regulate a multitude of cellular processes, such as survival, growth, motility, invasiveness, and angiogenesis. While the functions of PTEN have been studied extensively, the regulation of its activity during normal and disease conditions still remains incompletely understood. In this study, we identified the protein phosphatase-1 nuclear targeting subunit PNUTS (PPP1R10) as a PTEN-associated protein. PNUTS directly interacted with the lipid-binding domain (C2 domain) of PTEN and sequestered it in the nucleus. Depletion of PNUTS leads to increased apoptosis and reduced cellular proliferation in a PTEN-dependent manner. PNUTS expression was elevated in certain cancers compared with matched normal tissues. Collectively, our studies reveal PNUTS as a novel PTEN regulator and a likely oncogene. Cancer Res; 73(1); 205–14. ©2012 AACR.
SpliceArray Profiling of Breast Cancer Reveals a Novel Variant of NCOR2/SMRT That Is Associated with Tamoxifen Resistance and Control of ERα Transcriptional Activity
Authors: Zhang Luduo , Gong Chun , Lau Samantha L.Y. , Yang Nan , Wong Oscar G.W. , Cheung Annie N.Y. , Tsang Janice W.H. , Chan Kelvin Y.K. , Khoo Ui-Soon
Published: November 2012

Gene expression profiling aimed at classifying and prognosing breast cancer has yielded signatures with little, if any, concordance. However, expression arrays used in these studies do not discriminate alternate RNA splice isoforms that vary widely in cancer and may resolve this problem. In this study, we profiled splice isoforms in a panel of tamoxifen-sensitive and -resistant cell lines, defining a novel variant (BQ323636.1) of the nuclear receptor corepressor 2 (NCOR2) that was associated with tamoxifen resistance. Overexpression of this variant in a tamoxifen-sensitive cell line induced its resistance to tamoxifen. We confirmed our initial findings from cell lines in 77 breast tumors from a Chinese cohort, where BQ323636.1 expression was higher in tamoxifen-resistant patients than tamoxifen-sensitive patients. For patients who were estrogen receptor (ER)-positive and had received tamoxifen treatment, higher BQ323636.1 expression level correlated with distant metastasis. High expression level of BQ323636.1 was found to be associated with poorer overall and disease-free survival for patients who had received tamoxifen treatment. Notably, higher BQ323636.1 versus NCOR2 wild-type ratio was also associated with negative ER and progesterone receptor (PR) status, and triple-negative status (ER−/PR−/HER2− receptor status). Mechanistic investigations showed that under conditions of tamoxifen exposure, BQ323636.1 suppressed the transcriptional activity of ERα, exhibiting promoter-regulating functions. Our findings highlight a novel splice variant of the ERα corepressor NCOR2 as a candidate biomarker in breast cancer that not only predicts tamoxifen response but may be targeted to overcome tamoxifen resistance. Cancer Res; 73(1); 246–55. ©2012 AACR.
Identification of an Aurora Kinase Inhibitor Specific for the Aurora B Isoform
Authors: Xie Hua , Lee Mee-Hyun , Zhu Feng , Reddy Kanamata , Peng Cong , Li Yan , Lim Do Young , Joon Kim Dong , Li Xiang , Kang Soouk , Li Haitao , Ma Weiya , Lubet Ronald A. , Ding Jian , Bode Ann M. , Dong Zigang
Published: November 2012

Aurora kinases play an important role in chromosome alignment, segregation, and cytokinesis during mitosis. In the present study, we used a ligand docking method to explore the novel scaffold of potential Aurora B inhibitors. One thousand compounds from our in-house compound library were screened against the Aurora B structure and one compound, (E)-3-((E)-4-(benzo[d][1,3]dioxol-5-yl)-2-oxobut-3-en-1-ylidene)indolin-2-one (designated herein as HOI-07) was selected for further study. HOI-07 potently inhibited in vitro Aurora B kinase activity in a dose-dependent manner, without obvious inhibition of another 49 kinases, including Aurora A. This compound suppressed Aurora B kinase activity in lung cancer cells, evidenced by the inhibition of the phosphorylation of histone H3 on Ser10 in a dose- and time-dependent manner. This inhibition resulted in apoptosis induction, G2–M arrest, polyploidy cells, and attenuation of cancer cell anchorage-independent growth. Moreover, knocking down the expression of Aurora B effectively reduced the sensitivity of cancer cells to HOI-07. Results of an in vivo xenograft mouse study showed that HOI-07 treatment effectively suppressed the growth of A549 xenografts, without affecting the body weight of mice. The expression of phospho-histone H3, phospho-Aurora B, and Ki-67 was also suppressed in the HOI-07 treatment group. Taken together, we identified HOI-07 as a specific Aurora B inhibitor, which deserves further investigation. Cancer Res; 73(2); 716–24. ©2012 AACR.
Production of Gastrointestinal Tumors in Mice by Modulating Latent TGF-β1 Activation
Authors: Shibahara Kotaro , Ota Mitsuhiko , Horiguchi Masahito , Yoshinaga Keiji , Melamed Jonathan , Rifkin Daniel B.
Published: November 2012

TGF-β and its signaling pathways are important mediators in the suppression of cancers of the gastrointestinal tract. TGF-β is released from cells in a latent complex consisting of TGF-β, the TGF-β propeptide [latency associated protein (LAP)], and a latent TGF-β binding protein (LTBP). We previously generated mice in which the LTBP-binding cysteine residues in LAP TGF-β1 were mutated to serine precluding covalent interactions with LTBP. These Tgfb1C33S/C33S mice develop multiorgan inflammation and tumors consistent with reduced TGF-β1 activity. To test whether further reduction in active TGF-β levels would yield additional tumors and a phenotype more similar to Tgfb1−/− mice, we generated mice that express TGF-β1C33S and are deficient in either integrin β8 or TSP-1, known activators of latent TGF-β1. In addition, we generated mice that have one mutant allele and one null allele at the Tgfb1 locus, reasoning that these mice should synthesize half the total amount of TGF-β1 as Tgfb1C33S/C33S mice, and the amount of active TGF-β1 would be correspondingly decreased compared with Tgfb1C33S/C33S mice. These compound-mutant mice displayed more severe inflammation and higher tumor numbers than the parental Tgfb1C33S/C33S animals. The level of active TGF-β1 in compound mutant mice seemed to be decreased compared with Tgfb1C33S/C33S mice as determined from analyses of surrogate markers of active TGF-β, such as P-Smad2, C-Myc, KI-67, and markers of cell-cycle traverse. We conclude that these mutant mice provide a useful system for modulating TGF-β levels in a manner that determines tumor number and inflammation within the gastrointestinal tract. Cancer Res; 73(1); 459–68. ©2012 AACR.
Clinical and Radiological Features of Stroke Patients with Poor Outcomes Who Do Not Receive Intravenous Thrombolysis because of Mild Symptoms
Authors: Ohara Tomoyuki , Nagakane Yoshinari , Tanaka Eijiro , Morii Fukiko , Koizumi Takashi , Yamamoto Yasumasa
Published: November 2012

Background and Aims: A substantial proportion of patients who did not receive intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA), solely because of mild symptoms, can show poor outcome. The aim of our study was to analyze clinical and radiological features of the patients. Methods: We enrolled 72 patients between 2007 and 2009 who presented to our hospital within 3 h after stroke onset and who did not receive rtPA therapy solely because of mild symptoms (NIHSS score of ≤4 at rtPA decision), and examined detailed characteristics of patients with poor outcomes. Poor outcome was defined as a modified Rankin Scale score of ≥2 at 3 months after the stroke. Results: Eleven of 72 patients (15%) had poor outcomes. Major vessel occlusion was observed in 7 of the 11 patients. Neurological deterioration after admission was main reason for poor outcome. Infarct expansion in 6 patients (2 large artery diseases and 4 small vessel diseases) and distal embolism by clot migration in 3 patients led to neurological deterioration. Conclusions: Clinical and radiological features of mild stroke patients with poor outcomes, who did not receive rtPA therapy, were identified. In such patients, intravenous thrombolysis may be justified.
Alcohol Use and Hazardous Drinking among Medical Specialists
Authors: Joos Leen , Glazemakers Inge , Dom Geert
Published: November 2012

Background: Alcohol use among medical specialists remains a delicate topic. However, the number of prevalence studies remains very limited in Western European countries. Aims: To explore alcohol use and hazardous drinking among male and female medical specialists. Methods: All medical specialists in Belgium – a typical Western European country regarding alcohol use – were invited to participate. Alcohol use and abuse were measured using the Alcohol Use Disorder Identification Test (AUDIT) and the CAGE screen (acronym based on the four items it contains: ‘Cut down drinking’, ‘Annoyed by criticism’, ‘Guilty feelings’ and ‘Eye opener’). Results: A sample of 1,501 specialists completed the survey. The composition of the sample was comparable with that of the overall population of specialists in Belgium regarding gender, age and specialties. A proportion of 18% of the specialists could be classified as hazardous drinkers and 16.8% reported binge drinking at least once a month. Female medical specialists drank less than their male counterparts; however, a substantial proportion of female specialists (14.9%) displayed higher risk levels of hazardous drinking. Significant differences were found between specialties on the CAGE screen. Finally, younger medical specialists tended to display healthier alcohol use patterns compared with their older counterparts. Conclusion: Medical specialists tend to indulge in more hazardous drinking compared with the general population (10%). The alcohol use patterns of female doctors tend to move towards those of males.
Details of Treatment-Related Difficulties in Men with Anti-N-Methyl-d-Aspartate Receptor Encephalitis
Authors: Sakamoto Hikaru , Hirano Makito , Samukawa Makoto , Ueno Shuichi , Maekura Shunji , Fujimura Harutoshi , Kuwahara Motoi , Hamada Yukihiro , Isono Chiharu , Tanaka Keiko , Kusunoki Susumu , Nakamura Yusaku
Published: November 2012

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) antibody-associated encephalitis is an immunologic disease characterized by a female preponderance. Males are infrequently affected. The clinical symptoms of affected boys as well as girls have been summarized, and they have some clinical features distinct from those of adults. However, the characteristics of men have been described in only a few reports. We describe in detail four men with anti-NMDAR encephalitis who presented with several clinical features that complicated disease management and recovery, including venous thrombosis, bilateral hippocampal involvement, hypersexuality, and joint contracture. We also report the first detailed clinical information about a male patient who died of this disease. In addition, we summarize the clinical characteristics of five patients previously reported by others.
Can Cortical Silent Period and Motor Threshold Be Practical Parameters in the Comparison of Patients with Generalized Epilepsy and Patients with Psychogenic Non-Epileptic Seizures?
Authors: İpekdal İlker H. , Karadaş Ömer , Ulaş Ümit H. , Vural Okay
Published: November 2012

Background/Aim: This study aimed to compare the cortical excitability of patients with generalized tonic-clonic seizures (GTCSs) and that of patients with psychogenic non-epileptic seizures (PNESs). Methods: Patients were classified into groups according to their electroencephalogram (EEG) findings and seizure types: group 1 = GTCS with an abnormal EEG, group 2 = GTCS with a normal EEG and group 3 = PNES with a normal EEG. The control group included healthy volunteers with normal EEGs. Cortical silent period (CSP) and motor threshold (MT) were measured for all groups and the results were compared. Results: CSPs were significantly prolonged in groups 1 and 2 when compared with group 3 and the control group. No differences were found between the MT measurements of all groups. Conclusion: The prolongation of CSP may demonstrate the differences between the pathophysiological mechanisms of GTCS and those of PNES.