bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Merlin expression and high Survivin labeling index are indicators for poor prognosis in patients with malignant pleural mesothelioma
Authors: Meerang Mayura , Bérard Karima , Friess Martina , Bitanihirwe Byron K.Y. , Soltermann Alex , Vrugt Bart , Felley-Bosco Emanuela , Bueno Raphael , Richards William G. , Seifert Burkhardt , Stahel Rolf , Weder Walter , Opitz Isabelle
Published: June 2016

Introduction

Alterations of the tumor suppressor Neurofibromatosis type II (NF2) have been reported in about 40% of Malignant pleural mesothelioma (MPM) patients. NF2 (Merlin) deficiency leads to alterations of the Hippo pathway; resulting in activation of the oncogenic Yes Associated Protein‐1 (YAP1). Our aim was to investigate the association between these alterations and clinical outcomes.

Material and methods

Tissue microarrays composed of MPM tumors derived from 2 independent MPM cohorts were employed for this study. Immunohistochemical expression of Merlin, YAP1 and its target genes, Survivin and connective tissue growth factor (CTGF) were assessed in nuclear and cytoplasmic fractions. Cohort 1 was comprised of 145 patients intended to be treated with chemotherapy (CTX) followed by extrapleural pneumonectomy (EPP), thus both pre‐ and post‐CTX tissues were available. Cohort 2 was comprised of 59 patients treated with EPP followed by intraoperative hyperthermic cisplatin and/or adjuvant CTX and/or radiotherapy. Marker expression was quantified by means of labeling index (%) for nuclear Survivin and by H‐score for the other markers. The dichotomized marker expression was tested for the association with overall survival (OS) and freedom from recurrence (FFR).

Results

Kaplan–Meier survival curves revealed a significant association between low cytoplasmic Merlin expression in pre‐induction CTX tissues of cohort 1 with shorter FFR (p = 0.02) and OS (p = 0.03). The same tendency was observed in the chemotherapy naïve tissues obtained during EPP of cohort 2. Low nuclear Merlin expression in post‐CTX tissues (available from cohort 1 only) was associated with shorter FFR (p = 0.04) and OS (p = 0.05). High nuclear Survivin labeling indices in both pre‐ and post‐CTX tissues of cohort 1 was associated with shorter FFR (p = 0.02). In cohort 2, this was associated with both FFR and OS (p = 0.046 and p = 0.002, respectively). In multivariate analysis, low expression of cytoplasmic Merlin remained an independent prognosticator for shorter FFR of cohort 1 [hazard ratio (HR) = 0.5, 95% confidence interval (CI) = 0.3–0.9, p = 0.001] and OS [HR = 0.5, 95% CI = 0.3–1, p = 0.04]. High Survivin labeling index was an independent prognostic factor for shorter FFR in patients from cohort 1 [HR = 3.4, 95% CI = 1.7–6.8, p = 0.006] and shorter OS in patients from cohort 2 [HR = 2.35, 95% CI = 1.27–4.33, p = 0.006].

Conclusions

Our findings uncover the significance of Merlin protein expression and Survivin labeling index as prognosticators for poor clinical outcome in two independent MPM cohorts. If confirmed, these markers may be used to identify subgroups of patients benefitting from additional treatment.
The immunological landscape in necrotising enterocolitis
Authors: Cho Steven X. , Berger Philip J. , Nold-Petry Claudia A. , Nold Marcel F.
Published: June 2016

Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.
Institutional Transformation and Changing Networking Patterns in China
Authors: Zhang Jianjun , Zhao Wei , Zhang Yanlong
Published: June 2016

Drawing insights from the institutional embeddedness perspective, this article explores the changing patterns and significance of two types of strategic networking along with the institutional transformation in China. Using two-wave survey data on Chinese private firms, we find that after the state relaxed its control of resources the importance of networking with the state tends to decline, while ties with market actors become increasingly important. Determinants of network investment have shifted from managers’ perceived importance of different types of network ties to a firm's immediate institutional environment. Finally, the impact of networking on firm growth has also altered over time. These findings advance our understanding of the crucial role of the institutional environment in shaping firms’ networking strategies and have important theoretical and practical implications.
Commentary on the Enigma of Chinese Performance: Do Chinese Investors’ Reactions to Merger Announcements Accurately Reflect Prospects for Success?
Authors: Young Michael N.
Published: June 2016

Although McCarthy, Dolfsma, and Weitzel (2016) cover much ground in their study, in this commentary I focus on alternative explanations for the empirical results indicating that Chinese acquirers outperformed acquirers from other countries – particularly acquirers from the United States. First, based on research I have done with colleagues (e.g., Chen & Young, 2010; Young & McGuinness, 2001) and that of a doctoral student (Tang, 2016), I suggest that comparison of Chinese stock market reactions to merger announcements with stock market reactions to merger announcements from more mature markets, such as the United States, may create some misleading results. The Event Study Method (ESM) used in this study is a measure of investors’ short-term reactions to unanticipated events and it assumes that investors are capable of accurately evaluating such events (MacKinlay, 1997; McWilliams & Siegel, 1997). I suggest that, given the relative newness of Chinese stock markets, Chinese investors may have reacted more positively to merger announcements regardless of the mergers’ prospects for success. Second, similar to Shapiro and Li (2016), I suggest that stages of industry and organizational development better explain the actual motivation and success of Chinese acquirers than does a general theory of culture or corporate governance traditions.
Block copolymer synthesis by controlled/living radical polymerisation in heterogeneous systems
Authors: Jennings J. , He G. , Howdle S. M. , Zetterlund P. B.
Published: June 2016

We review the range of CLRP-controlled syntheses of block copolymer particles in dispersed systems, which are being exploited to create new opportunities for the design of nanostructured soft materials.
Temporal Airy pulses control cell poration
Authors: Courvoisier S. , Götte N. , Zielinski B. , Winkler T. , Sarpe C. , Senftleben A. , Bonacina L. , Wolf J. P. , Baumert T.
Published: June 2016

We show that spectral phase shaping of fs-laser pulses can be used to optimize laser-cell membrane interactions in water environment. The energy and peak intensity thresholds required for cell poration with single pulse in the nJ range can be significantly reduced (25% reduction in energy and 88% reduction in peak intensity) by using temporal Airy pulses, controlled by positive third order dispersion, as compared to bandwidth limited pulses. Temporal Airy pulses are also effective to control the morphology of the induced pores, with prospective applications from cellular to tissue opto-surgery and transfection.
Contributed Review: Experimental characterization of inverse piezoelectric strain in GaN HEMTs via micro-Raman spectroscopy
Authors: Bagnall Kevin R. , Wang Evelyn N.
Published: June 2016

Micro-Raman thermography is one of the most popular techniques for measuring local temperature rise in gallium nitride (GaN) high electron mobility transistors with high spatial and temporal resolution. However, accurate temperature measurements based on changes in the Stokes peak positions of the GaN epitaxial layers require properly accounting for the stress and/or strain induced by the inverse piezoelectric effect. It is common practice to use the pinched OFF state as the unpowered reference for temperature measurements because the vertical electric field in the GaN buffer that induces inverse piezoelectric stress/strain is relatively independent of the gate bias. Although this approach has yielded temperature measurements that agree with those derived from the Stokes/anti-Stokes ratio and thermal models, there has been significant difficulty in quantifying the mechanical state of the GaN buffer in the pinched OFF state from changes in the Raman spectra. In this paper, we review the experimental technique of micro-Raman thermography and derive expressions for the detailed dependence of the Raman peak positions on strain, stress, and electric field components in wurtzite GaN. We also use a combination of semiconductor device modeling and electro-mechanical modeling to predict the stress and strain induced by the inverse piezoelectric effect. Based on the insights gained from our electro-mechanical model and the best values of material properties in the literature, we analyze changes in the E2 high and A1 (LO) Raman peaks and demonstrate that there are major quantitative discrepancies between measured and modeled values of inverse piezoelectric stress and strain. We examine many of the hypotheses offered in the literature for these discrepancies but conclude that none of them satisfactorily resolves these discrepancies. Further research is needed to determine whether the electric field components could be affecting the phonon frequencies apart from the inverse piezoelectric effect in wurtzite GaN, which has been predicted theoretically in zinc blende gallium arsenide (GaAs).
Coherent states, quantum gravity, and the Born-Oppenheimer approximation. I. General considerations
Authors: Stottmeister Alexander , Thiemann Thomas
Published: June 2016

This article, as the first of three, aims at establishing the (time-dependent) Born-Oppenheimer approximation, in the sense of space adiabatic perturbation theory, for quantum systems constructed by techniques of the loop quantum gravity framework, especially the canonical formulation of the latter. The analysis presented here fits into a rather general framework and offers a solution to the problem of applying the usual Born-Oppenheimer ansatz for molecular (or structurally analogous) systems to more general quantum systems (e.g., spin-orbit models) by means of space adiabatic perturbation theory. The proposed solution is applied to a simple, finite dimensional model of interacting spin systems, which serves as a non-trivial, minimal model of the aforesaid problem. Furthermore, it is explained how the content of this article and its companion affect the possible extraction of quantum field theory on curved spacetime from loop quantum gravity (including matter fields).
Influence of annealing temperature and Sn doping on the optical properties of hematite thin films determined by spectroscopic ellipsometry
Authors: de Souza Lígia P. , Chaves Rodrigo O. G. , Malachias Angelo , Paniago Roberto , Ferreira Sukarno O. , Ferlauto Andre S.
Published: June 2016

Hematite (α-Fe2O3) thin films were prepared by sol-gel route and investigated for application in H2 generation by photo-assisted water splitting. The photoelectrochemical (PEC) performance was shown to increase significantly for films deposited on SnO2:F/glass subjected to high temperature (T) annealing (>750 °C). Strong correlation was found between photogenerated current, donor concentration, and Sn concentration as determined by Mott-Schottky analysis and X-ray photoelectron spectroscopy. The effects of thermal annealing and Sn addition in the resulting microstructure and optical properties of hematite films deposited on fused silica substrates were determined by a combination of structural characterization techniques and spectroscopic ellipsometry. Thermal annealing (>600 °C) induces a higher optical absorption that is associated directly to film densification and grain growth; however, it promotes no changes in the energy positions of the main Fe2O3 electronic transitions. The band gap energy was found to be 2.21 eV and independent of microstructure and of Sn concentration for all studied films. On the other hand, Sn can be incorporated in the Fe2O3 lattice for concentration up to Sn/Fe ∼2%, leading to an increase in energy split of the main absorption peak, attributed to a distortion of the Fe2O3 lattice. For higher concentrations, Sn incorporation leads to a reduction in absorption, associated with higher porosity and the formation of a secondary Sn-rich phase. In summary, the variation in the optical properties induced by thermal annealing and Sn addition cannot account for the order of magnitude increase of the current density generated by photoanodes annealed at high T (>750 °C); thus, it is concluded that the major contribution for the enhanced PEC performance comes from improved electronic properties induced by the n-type doping caused by Sn diffusion from the SnO2:F substrate.
Tunable unidirectional scattering of ellipsoidal single nanoparticle
Authors: Reena  , Kalra Yogita , Kumar Ajeet , Sinha R. K.
Published: June 2016

We report unidirectional scattering by tri-axial single ellipsoidal dielectric nanoparticle, which is applicable in the design and development of tunable, low-loss and ultra-compact nanoantennas. Based on the orientation and rotation of the ellipsoidal nanoparticle, three types of modes, one longitudinal mode and two transverse modes, have been excited. Electric and magnetic dipoles have been optically induced in the nanoparticle. Generalized Kerker's conditions have been applied at the interference of optically induced electric and magnetic dipoles. Azimuthally symmetric forward scattering with complete suppression of backward scattering using first Generalized Kerker's condition has been achieved at three different wavelengths for the allowed longitudinal mode and transverse modes in the optical region using single ellipsoidal nanoparticle. Due to 3-fold symmetry, forward scattering can be tuned at different wavelengths, using single ellipsoidal nanoparticle just by changing the direction of the incident electric field.
AZO/Ag/AZO anode for resonant cavity red, blue, and yellow organic light emitting diodes
Authors: Gentle A. R. , Yambem S. D. , Burn P. L. , Meredith P. , Smith G. B.
Published: June 2016

Indium tin oxide (ITO) is the transparent electrode of choice for organic light-emitting diodes (OLEDs). Replacing ITO for cost and performance reasons is a major drive across optoelectronics. In this work, we show that changing the transparent electrode on red, blue, and yellow OLEDs from ITO to a multilayer buffered aluminium zinc oxide/silver/aluminium zinc oxide (AZO/Ag/AZO) substantially enhances total output intensity, with better control of colour, its constancy, and intensity over the full exit hemisphere. The thin Ag containing layer induces a resonant cavity optical response of the complete device. This is tuned to the emission spectra of the emissive material while minimizing internally trapped light. A complete set of spectral intensity data is presented across the full exit hemisphere for each electrode type and each OLED colour. Emission zone modelling of output spectra at a wide range of exit angles to the normal was in excellent agreement with the experimental data and hence could, in principle, be used to check and adjust production settings. These multilayer transparent electrodes show significant potential for both eliminating indium from OLEDs and spectrally shaping the emission.
Negative differential resistance in three terminal photodetectors
Authors: Mikhelashvili V. , Meyler B. , Yofis S. , Padmanabhan R. , Eisenstein G.
Published: June 2016

A three terminal (transistor-like) photodetector fabricated on a silicon-on-insulator substrate with a high responsivity over a wide spectral range from ultraviolet to the near infrared is described. Even for low gate and drain voltages of −0.15 V and +1 V, respectively, its responsivity is 0.5 A/W at 315 nm, 0.63 A/W at 455 nm, and 0.26 A/W at 880 nm. Moreover, the device exhibits a negative differential resistance (due to Pt nano particles which are embedded within the gate dielectric) with large peak-to-valley current ratios of 60 in the dark and up to 140 under illumination. These values are several times larger than those obtained in alternative two or three terminal systems which are based on heterostructures or structures with extremely high doping regions that cause band-banding or resonant tunneling.
Enhanced dielectric breakdown performances of propylene carbonate modified by nano-particles under microsecond pulses
Authors: Hou Yanpan , Zhang Jiande , Zhang Zicheng
Published: June 2016

Propylene carbonate shows appealing prospects as an energy storage medium in the compact pulsed power sources because of its large permittivity, high dielectric strength, and broad operating temperature range. In this paper, TiO2 nano-particles coated with γ-aminopropyltriethoxylsilane coupling agent are homogeneously dispersed into propylene carbonate and these nano-fluids (NFs) exhibit substantially larger breakdown voltages than those of pure propylene carbonate. It is proposed that interfaces between nano-fillers and propylene carbonate matrix may provide myriad trap sites for charge carriers. The charge carriers can be easily captured at the interfaces between NFs and the electrode, resulting in an increased barrier height and suppressed charge carriers injection, and in the bulk of NFs, the charge carriers' mean free path can be greatly shortened by the scattering effect. As a result, in order for charge carriers acquiring enough energy to generate a region of low density (the bubble) and initiate breakdown in NFs, much higher applied field is needed.
Note: Rheological properties of structured fluids: Improvements on the slotted-plate apparatus
Authors: De Kee Daniel
Published: June 2016

This note is to report on improvements to the slotted-plate device that allows for the determination of viscosity and yield stress in structured systems such as suspensions and electro-rheological fluids. The improvements address the determination of very low yield stress values that occur, for example, with biological fluids, as well as viscosity measurements at extremely low shear rates.
Optimal spinneret layout in Von Koch curves of fractal theory based needleless electrospinning process
Authors: Yang Wenxiu , Liu Yanbo , Zhang Ligai , Cao Hong , Wang Yang , Yao Jinbo
Published: June 2016

Needleless electrospinning technology is considered as a better avenue to produce nanofibrous materials at large scale, and electric field intensity and its distribution play an important role in controlling nanofiber diameter and quality of the nanofibrous web during electrospinning. In the current study, a novel needleless electrospinning method was proposed based on Von Koch curves of Fractal configuration, simulation and analysis on electric field intensity and distribution in the new electrospinning process were performed with Finite element analysis software, Comsol Multiphysics 4.4, based on linear and nonlinear Von Koch fractal curves (hereafter called fractal models). The result of simulation and analysis indicated that Second level fractal structure is the optimal linear electrospinning spinneret in terms of field intensity and uniformity. Further simulation and analysis showed that the circular type of Fractal spinneret has better field intensity and distribution compared to spiral type of Fractal spinneret in the nonlinear Fractal electrospinning technology. The electrospinning apparatus with the optimal Von Koch fractal spinneret was set up to verify the theoretical analysis results from Comsol simulation, achieving more uniform electric field distribution and lower energy cost, compared to the current needle and needleless electrospinning technologies.
Thermoelectric characterization and fabrication of nanostructured p-type Bi0.5Sb1.5Te3 and n-type Bi2Te3 thin film thermoelectric energy generator with an in-plane planar structure
Authors: Park No-Won , Park Tae-Hyun , Ahn Jay-Young , Kang So-Hyeon , Lee Won-Yong , Yoon Young-Gui , Yoon Soon-Gil , Lee Sang-Kwon
Published: June 2016

This paper presents in-plane bismuth-telluride-based thermoelectric (TE) energy generators fabricated using metal-shadow and radio-frequency sputtering methods at room temperature. The TE energy generators consist of four couples of 300-nm-thick nanostructured Bi2Te3 (n-BT) and Bi0.5Sb1.5Te3 (p-BST) thin films used as n-type and p-type materials, respectively, on a Si substrate for the p/n junctions of the TE energy generators. Furthermore, the effect of annealing treatment of both n-BT and p-BST thin films on the electrical and TE properties as well as the TE performance of the TE energy generators is discussed. By varying the temperature between the hot and cold junction legs of the n-BT/p-BST in-plane TE energy generators annealed at 200 °C, the maximum output voltage and power are determined to be ∼3.6 mV and ∼1.1 nW, respectively, at a temperature difference of 50 K. The output powers increased by ∼590% compared to that of the as-grown TE generator at a temperature difference of 90 K. This improvement in the TE performance is attributed to the enhancement of the electrical conductivity after heat treatment. From a numerical simulation conducted using a commercial software (COMSOL), we are confident that it plays a crucial role in determining the dimension (i.e., thickness of each leg) and material properties of both n-BT and p-BST materials of the in-plane TE energy generators.
Electrical properties and interfacial issues of high-k/Si MIS capacitors characterized by the thickness of Al2O3 interlayer
Authors: Wang Xing , Liu Hongxia , Fei Chenxi , Zhao Lu , Chen Shupeng , Wang Shulong
Published: June 2016

A thin Al2O3 interlayer deposited between La2O3 layer and Si substrate was used to scavenge the interfacial layer (IL) by blocking the out-diffusion of substrate Si. Some advantages and disadvantages of this method were discussed in detail. Evident IL reduction corroborated by the transmission electron microscopy results suggested the feasibility of this method in IL scavenging. Significant improvements in oxygen vacancy and leakage current characteristics were achieved as the thickness of Al2O3 interlayer increase. Meanwhile, some disadvantages such as the degradations in interface trap and oxide trapped charge characteristics were also observed.
Rheopectic Gel Formation of Stimuli-Responsive Ionic Liquid/Water Mixtures
Authors: Fukaya Yukinobu , Nakano Takuro , Ohno Hiroyuki
Published: June 2016

A new class of hydrophobic and polar ionic liquids was prepared by coupling hydrophobic tetraoctylphosphonium cation and polar phosphonate-derived anions. Mixtures of these ionic liquids and water showed lower critical solution temperature-type phase behaviour. Furthermore, these mixtures displayed thermoreversible, however, non-linear viscosity change despite their large content of water. The abrupt increase in the viscosity was explained by the occurrence of rheopectic gelation of the ionic liquid/water mixtures by external stimuli such as shear stress.
Organometallic Complexes for Non-Linear Optics. 59. Syntheses and Optical Properties of Some Octupolar (N-Heterocyclic Carbene)gold Complexes
Authors: Liu Gang , Quintana Cristóbal , Wang Genmiao , Kodikara Mahesh S. , Du Jun , Stranger Rob , Zhang Chi , Cifuentes Marie P. , Humphrey Mark G.
Published: June 2016

The syntheses of octupolar alkynes 1,3,5-{4-(4-HC≡CC6H4-1-C≡C)-3,5-Et2C6H2-1-C≡C}3C6H3 (4) and 1,3,5-{4-(4-HC≡CC6H4-1-C≡C-4-C6H4-1-C≡C)-3,5-Et2C6H2-1-C≡C}3C6H3 (6), diphenylamino-substituted 1,3,5-(4-Ph2NC6H4-1-C≡C)3C6H3 (7), 1,3,5-(4-Ph2NC6H4-1-C≡C-4-C6H4-1-C≡C)3C6H3 (8), 1,3,5-{4-(4-Ph2NC6H4-1-C≡C-4-C6H4-1-C≡C)-3,5-Et2C6H2-1-C≡C}3C6H3 (9), and 1,3,5-{4-(4-Ph2NC6H4-1-C≡C-4-C6H4-1-C≡C-4-C6H4-1-C≡C)-3,5-Et2C6H2-1-C≡C}3C6H3 (10), and (N-heterocyclic carbene)gold-appended 1,3,5-{[(NHC-iPr)Au]C≡C}3C6H3 (11), 1,3,5-{[(NHC-iPr)Au]C≡C-4-C6H4-1-C≡C}3C6H3 (12), 1,3,5-{4-([(NHC-iPr)Au]C≡C-4-C6H4-1-C≡C)-3,5-Et2C6H2-1-C≡C}3C6H3 (13), and 1,3,5-{4-([(NHC-iPr)Au]C≡C-4-C6H4-1-C≡C-4-C6H4-1-C≡C)-3,5-Et2C6H2-1-C≡C}3C6H3 (14) [NHC-iPr = κC-cyclo-CN(2,6-C6H3iPr2)CH=CHN(2,6-C6H3iPr2)] are reported. The low-energy bands in the linear optical absorption spectra of all three sets of compounds are red-shifted and increase in intensity upon π-delocalizable ‘arm’ lengthening. The diphenylamino- and (NHC-iPr)gold-terminated compounds do not exhibit measurable second-harmonic generation as assessed by hyper-Rayleigh scattering at 1064 nm using nanosecond pulses. Computational studies have been employed to rationalize the optical properties of the new compounds. Calculations on 7–10 reveal that the lowest-energy transitions with large oscillator strengths are predominantly [Ph2NC6H4] (π) → [arms + core] (π*) in character, whereas calculations on 11–14 suggest that the low-energy transitions relate to the transfer of electron density from the Au-alkynyl core group to the terminal NHC groups.
Phospholipase Cβ1 induces membrane tubulation and is involved in caveolae formation
Authors: Inaba Takehiko , Kishimoto Takuma , Murate Motohide , Tajima Takuya , Sakai Shota , Abe Mitsuhiro , Makino Asami , Tomishige Nario , Ishitsuka Reiko , Ikeda Yasuo , Takeoka Shinji , Kobayashi Toshihide
Published: June 2016

Significance

Lipid membrane curvature plays important roles in various physiological phenomena. Using darkfield microscopy, we performed nonbiased screening of a protein that induces deformations of nonlabeled liposomes. We identified phospholipase Cβ1 (PLCβ1), which induces tubulation of the phosphatidylethanolamine and phosphatidylserine-containing membranes. The characteristic C-terminal sequence of PLCβ1, but not the conserved inositol phospholipid-binding pleckstrin homology (PH) domain or catalytic domains of PLCβ1, is involved in the tubulation of liposomes. The C-terminal sequence is predicted to have the Bin/amphiphysin/Rvs (BAR)-like conformation by computational modeling. Our results indicate that sensing and modulation of the curvature by the C-terminal BAR-like domains is involved in the activation of PLCβ1. The present results also reveal the role of PLCβ1 in caveolae formation.
Diagnostic features of English-lexifier Creoles
Authors: Avram Andrei A.
Published: June 2016

This paper analyzes the attestations in Antiguan of the diagnostic features of English-lexifier contact languages, as proposed by Baker and Huber (2001). It compares the distribution of these features in Antiguan and the seven Atlantic English-lexifier Pidgins and Creoles considered by Baker and Huber (2001). The features identified serve as quantitative measures of the affinity between Antiguan and two Creoles, Bajan and Kittitian, which contributed to its emergence, and between Antiguan and Vincentian, a Creole with significant Antiguan input. A number of selected diagnostic features found in Antiguan are discussed. It is shown that data from Antiguan are relevant to the distribution of diagnostic features across English-lexifier Pidgins and Creoles as well as to their adequate classification.
A Late 19th-Century British Perspective on Modern Foreign Language Learning, Teaching, and Reform
Authors: Perlman Lorch Marjorie
Published: June 2016

The late 19th century saw a great rise in private foreign language learning and increasing provision of Modern foreign language teaching in schools. Evidence is presented to document the uptake of innovations in Thomas Prendergast’s (1807–1886) “Mastery System” by both individual language learners and educationalists. Although it has previously been suggested that Prendergast’s method failed to have much impact, this study clearly demonstrates the major influence he had on approaches to language learning and teaching in Britain and around the world both with his contemporaries and long after his death. This detailed case study illuminates the landscape of modern language pedagogy in Victorian Britain.
Diagnosing focus
Authors: van der Wal Jenneke
Published: June 2016

Many tests have been used in eliciting focus constructions and determining what type of focus a certain linguistic strategy expresses. This paper provides an overview of the various diagnostics for focus, indicating how they show the size of the focused constituent and what semantic-pragmatic type of focus is expressed. These types range from simple pragmatic focus to semantically more complex focus, signalling exclusivity or exhaustivity either as an inherent semantic part of the focus, or merely an implicature. The discussion of these diagnostics brings to light how some diagnostics are flawed, and whether the linguistic strategy tested is actually a dedicated strategy for focus at all.
Contrastive focus-marking and nominalization in Northern Kampa (Arawak) of Peru
Authors: Mihas Elena
Published: June 2016

This study examines the interaction of contrastive focus-marking with nominalization in bisected contrastive focus constructions of Alto Perené, a Kampa Arawak language of Peru. It also investigates morphosyntactic means of contrastive focus-marking in two neighboring Kampa languages, Ashéninka Pichis and Ashaninka Tambo. The languages are shown to employ various focus-marking strategies. The Alto Perené polar (truth value) focus construction shows a preference for nominalizing a lexical verb. In Ashaninka Tambo, the expression of polar and modal operator focus (the latter attested in negated clauses) does not require nominalization of the lexical verb, but in clefted content and polar questions and affirmative declarative clauses, nominalization is mandatory for the purpose of argument focusing. In Ashéninka Pichis, the argument focus-marking strategies include the syntactic movement of the focus constituent to the preverbal focus position and either an elision of the subject index on the verb, or inflecting the verb for stative aspect.
Dose–volume analysis of predictors for chronic gastrointestinal complications in patients with cervical cancer treated with postoperative concurrent chemotherapy and whole-pelvic radiation therapy
Authors: Isohashi Fumiaki , Mabuchi Seiji , Akino Yuichi , Yoshioka Yasuo , Seo Yuji , Suzuki Osamu , Tamari Keisuke , Yoshino Kiyoshi , Sawada Kenjiro , Ueda Yutaka , Kobayashi Eiji , Sumida Iori , Mizuno Hirokazu , Okubo Hirofumi , Kimura Tadashi , Ogawa Kazuhiko
Published: June 2016

The purpose of this study is to evaluate dose–volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in patients with cervical cancer who have undergone postoperative concurrent chemotherapy and whole-pelvic radiation therapy (WPRT). The subjects were 135 patients who had undergone postoperative WPRT with concurrent nedaplatin-based chemotherapy between 2000 and 2014. Associations between selected DVH parameters and the incidence of chronic GI complications of G3 or higher were evaluated. Chronic GI complications of severity G3 occurred in 18 (13%) patients. Patients with GI complications had significantly greater V5–V45, mean dose and the generalized equivalent uniform dose (gEUD) of the small bowel loops, compared with those without GI complications. V30–V45, mean dose and gEUD of the bowel bag also showed significant differences between patients with and without GI complications. In contrast, no parameter for the large bowel loop was correlated with GI complications. Receiver operating characteristics curve analysis indicated that V30–V45 of the small bowel loops were better predictors than these respective parameters for the bowel bag. Next, patients were divided into four groups based on the median V15 and V40 of the small bowel loops. The group with both a high V15 and a high V40 showed a significantly higher probability of chronic GI complications. In conclusion, the small bowel loops are better predictors of chronic GI complications compared with the bowel bag, and a relatively high-dose volume (e.g. V40) of the small bowel loops is a useful predictor of chronic GI complications.
From Bench to Bedside and Back Again
Authors: Maze Mervyn
Published: June 2016

Dexmedetomidine Diminishes Halothane Anesthetic Requirements in Rats Through a Postsynaptic Alpha 2 Adrenergic Receptor. By Segal IS, Vickery RG, Walton JK, Doze VA, and Maze M. Anesthesiology 1988; 125:590–4. Abstract reprinted with permission.

The effect of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole (medetomidine), the α2 adrenergic agonist, on anesthetic requirements was investigated in rats anesthetized with halothane. Halothane MAC was determined before and after either dexmedetomidine (d-enantiomer) or levomedetomidine (l-enantiomer) 10, 30, and 100 μg/kg, or vehicle intraperitoneally. There was a dose-dependent increase in MAC with the d-, but not the l-, stereoisomer. At the highest dose of dexmedetomidine (100 μg/kg), halothane could be discontinued for up to 30 min with no response to tail clamping. To determine whether α2 adrenoreceptors mediated this effect of dexmedetomidine on MAC, cohorts of rats were pretreated with idazoxan, 10 mg/kg intraperitoneally, a highly selective α2 antagonist. This completely prevented the reduction of MAC caused by dexmedetomidine. To determine whether the reduction of MAC caused by dexmedetomidine was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg intraperitoneally, an opiate antagonist, or 8-phenyltheophylline, 2.5 mg/kg intraperitoneally, an A1 adenosine antagonist. These two pretreatments did not alter the reduction of MAC by dexmedetomidine. To determine whether postsynaptic mechanisms mediate the anesthetic effect of dexmedetomidine, rats were depleted of central catecholamine stores with either n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine or reserpine and α-methyl-para-tyrosine, and MAC was determined before and after each dose of dexmedetomidine. While the catecholamine-depleted rats had a lower basal MAC than the vehicle controls, there was still a profound reduction in halothane MAC after administration of dexmedetomidine. The reduction of MAC by dexmedetomidine was blocked with idazoxan in the catecholamine-depleted rats. These data indicate that the reduction of MAC caused by dexmedetomidine is mediated through α2 adrenoreceptors with no apparent involvement of either opiate or A1 adenosine receptors. Data from catecholamine-depleted rats suggest that the mediating mechanism must involve site(s) other than or in addition to the presynaptic α2 adrenergic receptors on noradrenergic neurons. The authors conclude that central postsynaptic α2 adrenergic receptors mediate a significant part of the reduction of anesthetic requirements caused by dexmedetomidine.
SCLEROMYXEDEMA WITH RETINAL VASCULITIS AND MACULAR EDEMA
Authors: Gutiérrez-Aguirre Karen I. , Stewart Michael W. , Sluzevich Jason C.
Published: June 2016

Background/Purpose:

To describe the findings and clinical course of a patient with scleromyxedema complicated by retinal vasculitis and macular edema.

Methods:

Interventional case report.

Results:

A 64-year old Caucasian woman with recently diagnosed, biopsy proven scleromyxedema presented with decreased visual acuity (20/50 OD; 20/100 OS) due to retinal vasculitis and macular edema. She received intravitreal bevacizumab and subtenon's triamcinolone acetonide for the macular edema, and bilateral pars plana vitrectomies were required for vitreous hemorrhages. Monthly intravenous infusions of immunoglobulins (IVIG) resulted in resolution of the macular edema and vasculitis, and stabilization of the VA (20/40 OD; counting fingers at 6 feet OS).

Conclusion:

Scleromyxedema may be complicated by retinal vasculitis and macular edema. Treatment with corticosteroids and vascular endothelial growth factor inhibitors may be minimally effective but IVIG should be considered for both the ocular and systemic findings.
Disseminated Aspergillosis in a Previously Immunocompetent Host: A Case Report
Authors: Smith Joshua , Noor Aliya , Hage Chadi
Published: June 2016

Aspergillus infection can manifest in a variety of ways ranging from allergic bronchopulmonary aspergillosis to disseminated aspergillosis. Invasive disease is typically seen in the immunocompromised population but may rarely affect immunocompetent hosts. We present a case of a 48-year-old previously healthy man initially presenting with septic shock and multiorgan system failure. After stabilization, he developed persistent fevers with worsening mental status. Imaging of the brain revealed multiple hemorrhages with impending brain herniation. Postmortem examination revealed purulent abscesses in multiple organs with culture and microscopic evaluation revealing Aspergillus fumigatus.
Gamma-rhythmic Gain Modulation
Authors: Ni Jianguang , Wunderle Thomas , Lewis Christopher M. , Desimone Robert , Diester Ilka , Fries Pascal
Published: June 2016

Cognition requires the dynamic modulation of effective connectivity, i.e. the modulation of the postsynaptic neuronal response to a given input. If postsynaptic neurons are rhythmically active, this might entail rhythmic gain modulation, such that inputs synchronized to phases of high gain benefit from enhanced effective connectivity. We show that visually induced gamma-band activity in awake macaque area V4 rhythmically modulates responses to unpredictable stimulus events. This modulation exceeded a simple additive superposition of a constant response onto ongoing gamma-rhythmic firing, demonstrating the modulation of multiplicative gain. Gamma phases leading to strongest neuronal responses also led to shortest behavioral reaction times, suggesting functional relevance of the effect. Furthermore, we find that constant optogenetic stimulation of anesthetized cat area 21a produces gamma-band activity entailing a similar gain modulation. As the gamma rhythm in area 21a did not spread backwards to area 17, this suggests that postsynaptic gamma is sufficient for gain modulation.
Comparative analysis highlights variable genome content of wheat rusts and divergence of the mating loci
Authors: Cuomo Christina A. , Bakkeren Guus , Khalil Hala Badr , Panwar Vinay , Joly David , Linning Rob , Sakthikumar Sharadha , Song Xiao , Adiconis Xian , Fan Lin , Goldberg Jonathan M. , Levin Joshua Z. , Young Sarah , Zeng Qiandong , Anikster Yehoshua , Bruce Myron , Wang Meinan , Yin Chuntao , McCallum Brent , Szabo Les J. , Hulbert Scot , Chen Xianming , Fellers John P.
Published: June 2016

Three members of thePuccinigenus,P. triticina(Pt),P. striiformis f.sp. tritici(Pst), andP. graminis f.sp. tritici(Pgt), cause the most common and often most significant foliar diseases of wheat. While similar in biology and life cycle, each species is uniquely adapted and specialized. The genomes ofPtandPstwere sequenced and compared to that ofPgtto identify common and distinguishing gene content, to determine gene variation among wheat rust pathogens, other rust fungi and basidiomycetes, and to identify genes of significance for infection.Pthad the largest genome of the three, estimated at 135 Mb with expansion due to mobile elements and repeats encompassing 50.9% of contig bases; by comparison repeats occupy 31.5% forPstand 36.5% forPgt. We find all three genomes are highly heterozygous, withPst(5.97 SNPs/kb) nearly twice the level detected inPt(2.57 SNPs/kb) and that previously reported forPgt. Of 1,358 predicted effectors inPt, 784 were found expressed across diverse life cycle stages including the sexual stage. Comparison to related fungi highlighted the expansion of gene families involved in transcriptional regulation and nucleotide binding, protein modification, and carbohydrate enzyme degradation. Two allelic homeodomain, HD1 and HD2, pairs and three pheromone receptor (STE3) mating-type genes were identified in each dikaryoticPucciniaspecies. The HD proteins were active in a heterologousUstilago maydismating assay and host induced gene silencing of the HD andSTE3alleles reduced wheat host infection.
The Impact of the Minimum Legal Drinking Age on Alcohol‐Related Chronic Disease Mortality
Authors: Plunk Andrew D. , Krauss Melissa J. , Syed‐Mohammed Husham , Hur Michael , Cavzos‐Rehg Patricia A. , Bierut Laura J. , Grucza Richard A.
Published: June 2016

Background

The minimum legal drinking age (MLDA) of 21 has been associated with a number of benefits compared to lower MLDAs, including long‐term effects, such as reduced risk for alcoholism in adulthood. However, no studies have examined whether MLDA during young adulthood is associated with mortality later in life. We examined whether individuals exposed to permissive MLDA (<21) had higher risk of death from alcohol‐related chronic disease compared to those exposed to the 21 MLDA. Because prior work suggests that MLDA affects college students differently, we also conducted conditional analyses based on ever having attended college.

Methods

Data from the 1990 through 2010 U.S. Multiple Cause‐of‐Death files were combined with data on the living population and analyzed. We included individuals who turned 18 during the years 1967 to 1990, the period during which MLDA varied across states. We examined records on death from several alcohol‐related chronic diseases, employing a quasi‐experimental approach to control for unobserved state characteristics and stable time trends.

Results

Individuals who reported any college attendance did not exhibit significant associations between MLDA and mortality for the causes of death we examined. However, permissive MLDA for those who never attended college was associated with 6% higher odds for death from alcoholic liver disease, 8% higher odds for other liver disease, and 7% higher odds for lip/oral/pharynx cancers (odds ratio [OR] = 1.06, 95% confidence interval [CI] [1.02, 1.10]; OR = 1.08, 95% CI [1.03, 1.13]; OR = 1.07, 95% CI [1.03, 1.12], respectively).

Conclusions

The 21 MLDA likely protects against risk of death from alcohol‐related chronic disease across the lifespan, at least for those who did not attend college. This is consistent with other work that shows that the long‐term association between MLDA and alcohol‐related outcomes is specific to those who did not attend college.
Wildlife Habitat Is Similar at Mined Versus Unmined Sites 30 Years Following Surface Mining for Coal in Southern Illinois
Authors: Nielsen Clayton K. , Kelly Veronica L.
Published: June 2016

Riparian ecosystems provide important habitat for wildlife and serve as corridors for animal movements. Surface mining activities clearly impact wildlife habitat by removing vegetation needed by wildlife. However, few studies have assessed longer‐term success of habitat restoration in riparian ecosystems following surface mining. During 2012–13, we evaluated microhabitat quality at three stream segments restored 30 years ago following surface mining for coal and one unmined stream segment in Perry County, Illinois. Microhabitat differences were very minor among restored and control stream sites. Of the 41 habitat variables measured, 14 differed among sites, four of which were uncorrelated: canopy cover, overstory hard mast, bare ground, and herbaceous ground cover; thus, restored riparian buffers were comparable to unmined sites, indicating that habitat restoration efforts were successful. Our analysis from data collected at Burning Star 4 mine in Perry County, Illinois, is of value to land managers for it shows how the reclamation process has successfully jump‐started wildlife habitat in buffers around streams affected by mining.
Historical biogeography of the short‐faced scorpionflies (Insecta: Mecoptera: Panorpodidae)
Authors: Hu Gui‐Lin , Hua Bao‐Zhen
Published: June 2016

Aim

Panorpodidae is a species‐poor family of Mecoptera, containing only 13 species in its two genera, Panorpodes and Brachypanorpa. They are found disjunctly in eastern Asia and North America, and this distribution has been deeply affected by the region's complex geological and climatic history. We calculate a time‐calibrated molecular phylogeny and use it to reconstruct the historical biogeography of the Panorpodidae, in order to explore the family's phylogenetic origin and the biogeographical process that resulted in the present disjunct distribution.

Location

Eastern Asia and North America.

Methods

Sequence data from mitochondrial (COI and COII) and nuclear DNA (28S and EF‐1α) were assembled from eight ingroup species. A phylogeny was reconstructed using maximum‐likelihood analysis and Bayesian inference, and divergence times were estimated using fossil‐calibrated Bayesian analysis. Ancestral areas were reconstructed with rasp 3.02, implementing dispersal–vicariance analysis, dispersal–extinction–cladogenesis and Bayesian binary MCMC.

Results

The initial diversification of Panorpodidae occurred during the Ypresian (c. 53.9 Ma). A wide ancestral distribution in eastern Asia and western North America was inferred from the biogeographical analyses. The original range of Panorpodes across eastern Asia and western North America was fragmented by intercontinental vicariance. The genus Brachypanorpa was initially restricted to western North America and subsequently dispersed into eastern regions of North America.

Main conclusions

Two alternative biogeographical patterns were recovered. Either Panorpodidae was restricted to western North America in the Eocene and subsequently dispersed into eastern Asia or – more reasonably – it was widely distributed in western North America, eastern Asia and Europe during the Eocene. Our biogeographical reconstructions corroborate the significant role of vicariance in shaping the current eastern Asian and North American disjunction in Panorpodes. The geographical separation of western and eastern North American Brachypanorpa species is likely to have resulted from the uplift of the Rocky Mountains and the emergence of grassland biomes in central North America.