bluuebunny/crossref_metadata_2025 huggingface dataset:
COMMUNICATIVE FOCUS ON FORM AND SECOND LANGUAGE SUPRASEGMENTAL LEARNING
Authors: Saito Kazuya , Wu Xianghua
Published: May 2014

The current study examined how form-focused instruction (FFI) with and without corrective feedback (CF) as output enhancement facilitated second language (L2) perception of Mandarin tones at both the phonetic and phonological levels by 41 Cantonese learners of Mandarin. Two experimental groups, FFI only and FFI-CF, received a 90-min FFI treatment designed to encourage them to notice and practice the categorical distinctions of Mandarin tones through a range of communicative input and output activities. During these activities, the instructors provided CF only to students in the FFI-CF group by recasting and pushing them to repair their mispronunciations of the target features (i.e., output enhancement). The control group received comparable meaning-oriented instruction without any FFI. The effectiveness of FFI was assessed via a forced-choice identification task with both trained and untrained items for a variety of tonal contrasts in Mandarin (high-level Tone 1 vs. mid-rising Tone 2 vs. high-falling Tone 4). According to statistical comparisons, the FFI-only group attained significant improvement in all lexical and tonal contexts, and such effectiveness was evident particularly in the acquisition of Tone 1 and Tone 4—supposedly the most difficult instances due to their identical phonological status in the learners’ first language, Cantonese. The FFI-CF group, however, demonstrated marginally significant gains only under the trained lexical conditions. The results suggest that FFI promotes learners’ attentional shift from vocabulary to sound learning (generalizable gains in trained and untrained items) and facilitates their access to new phonetic and phonological categories. Yet the relative advantage of adding CF to FFI as output enhancement remains unclear, especially with respect to the less experienced L2 learners in the current study.
Expression Profile and Subcellular Localization of GAPDH in the Smooth Muscle Cells of Human Atherosclerotic Plaque: An Immunohistochemical and Ultrastructural Study with Biological Therapeutic Perspectives
Authors: Perrotta Ida , Aquila Saveria , Mazzulla Sergio
Published: May 2014

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been considered a classical glycolytic enzyme involved exclusively in cytosolic energy production. Several recent studies, however, have demonstrated that GAPDH is a multifunctional protein whose presence and activity can be regulated by disease states and/or experimental manipulation. Expression levels of GAPDH have been shown to be altered in certain tumors as well as in proliferating and differentiating cells. Since dedifferentiation and proliferation of smooth muscle cells (SMCs) are important features of human atherosclerosis, we have characterized the expression profile of GAPDH in the SMCs of atherosclerotic plaques and its putative interrelationship with the synthetic/proliferative status of these cells utilizing the proliferating cell nuclear antigen (PCNA) antibody, a valuable marker of cell proliferation. Western blot data revealed that GAPDH was significantly upregulated in atherosclerotic plaque specimens. Immunohistochemical stains demonstrated that GAPDH accumulated in the nucleus of dedifferentiated SMCs that also showed positive immunoreactivity for PCNA, but remained cytoplasmatic in the contractile SMCs (PCNA-negative), thus reflecting the proliferative, structural and synthetic differences between them. We suggest that, in human atherosclerotic plaque, GAPDH might exert additional functions that are independent of its well-documented glycolytic activity and might play key roles in development of the disease.
Introduction to the special issue on probability, logic and learning
Authors: CUSSENS JAMES , DE RAEDT LUC , KIMMIG ANGELIKA , SATO TAISUKE
Published: May 2014

Recently, the combination of probability, logic and learning has received considerable attention in the artificial intelligence and machine learning communities; see e.g. Getoor and Taskar (2007); De Raedt et al. (2008). Computational logic often plays a major role in these developments since it forms the theoretical backbone for much of the work in probabilistic programming and logical and relational learning. Contemporary work in this area is often application- and experiment-driven, but is also concerned with the theoretical foundations of formalisms and inference procedures and with advanced implementation technology that scales well.
„Endlich kann ich mal komplett pflegen“
Authors: Zinndorf Silvia , Arend Anke , Jochum Simone , Utsch Anika
Published: May 2014

Eine erfolgreiche Ausbildung in der Gesundheits- und Krankenpflege hängt maßgeblich von der Vernetzung der Lernorte Schule und Praxis ab. Eine Möglichkeit, um der praktischen Ausbildung in der Pflege mehr Gewicht zu geben, stellt das Konzept der Bereichspflegeanleitung dar. Als Weiterentwicklung bietet die Schulstation die Möglichkeit, die Lernchancen allen Auszubildenden zugänglich zu machen. Im Folgenden werden die Konzepte der Bereichspflegeanleitung und Schulstation näher vorgestellt.
A quantum dot based electrochemiluminescent immunosensor for the detection of pg level phenylethanolamine A using gold nanoparticles as substrates and electron transfer accelerators
Authors: Yan Panpan , Zhang Jing , Tang Qinghui , Deng Anping , Li Jianguo
Published: May 2014

This study reports the development of an electrochemiluminescent (ECL) immunosensor for ultrasensitive detection of phenylethanolamine A (PA) based on CdSe quantum dots (QDs) and gold nanoparticles (GNPs).
Control of emission colour with N-heterocyclic carbene (NHC) ligands in phosphorescent three-coordinate Cu(i) complexes
Authors: Krylova Valentina A. , Djurovich Peter I. , Conley Brian L. , Haiges Ralf , Whited Matthew T. , Williams Travis J. , Thompson Mark E.
Published: May 2014

A series of three phosphorescent mononuclear (NHC)–Cu(i) complexes were prepared and characterized.
The evolution of life cycle assessment in pharmaceutical and chemical applications – a perspective
Authors: Jiménez-González Concepción , Overcash Michael R.
Published: May 2014

A perspective on life cycle assessment in pharmaceutical and chemical industries, including evolution, lessons learned and future needs.
Exploring mutasynthesis to increase structural diversity in the synthesis of highly oxygenated polyketide lactones
Authors: Botubol-Ares J. M. , Durán-Peña M. J. , Macías-Sánchez A. J. , Hanson J. R. , Collado I. G. , Hernández-Galán R.
Published: May 2014

Four new highly oxygenated 11-membered lactones (11–14) were synthesized by a combination of metabolic engineering techniques with complex chemical substrate synthesis.
Nanoflaky MnO2grown in situ on carbon microbeads as an anode material for high-performance lithium-ion batteries
Authors: Wang Hao , Liu Jing , Wang Xianyou , Wu Chun , Zhao Qinglan , Fu Yanqing , Yang Xiukang , Shu Hongbo
Published: May 2014

A flower-like MnO2/CMB nanocomposite is synthesizedvia in situgrowth of birnessite-type MnO2on the surface of monodisperse carbon microbeads.
Electric field control of the optical properties in magnetic mixed-valence molecules
Authors: Palii Andrew , Clemente-Juan Juan M. , Tsukerblat Boris , Coronado Eugenio
Published: May 2014

In delocalized magnetic mixed-valence molecules the spin-crossover induced by an electric field may have a strong influence on their optical properties.
Gastric mucosal inflammatory responses to Helicobacter pylori.
Authors: Crabtree JE
Published: May 2014

Within the gastroduodenal mucosa Helicobacter pylori infection stimulates local production of a range of proinflammatory and immunoregulatory cytokines, neutrophil infiltration, specific T‐ and B‐ cell responses and the development of gastric lymphoid follicles. Following bacterial eradication this mucosal inflammatory response resolves. Infiltrating neutrophils are likely to be one of the major mediators of mucosal damage. Neutrophil activation, including reactive oxygen metabolite production and the release of myeloperoxidase, will be induced directly by bacterial factors and indirectly through products of complement activation, bioactive lipids and host‐derived cytokines. Interleukin‐8, and related peptides of the chemokine family secreted by gastric epithelial cells, are likely to be important host mediators inducing neutrophil migration to sites of infection. Epithelial IL‐8 is upregulated by TNF‐alpha and IL‐1 and directly by H. pylori strains expressing the CagA phenotype. The extent of mucosal injury may reflect bacterial density, the variability of different strains of H. pylori to induce chemokine expression in epithelial cells and the oxidative burst in neutrophils. Recent evidence from in vivo and in vitro studies shows that CagA+ VacA+ strains of H. pylori are associated with enhanced inflammatory responses and mucosal damage. Defining the specific bacterial mediators of mucosal inflammation will be important in elucidating the role of H. pylori in the pathogenesis of gastroduodenal disease.
Secure multiple‐input single‐output communication – Part I: secrecy rates and switched power allocation
Authors: Van Nguyen Thang , Jeong Youngmin , Kwak Jin Sam , Shin Hyundong
Published: May 2014

The use of multiple‐antenna arrays has attracted much attention for the physical layer security of wireless systems, where the so‐called artificial‐noise solution can be applied to enhance the communication confidentiality. In the first part of this study, the authors consider secure communication over a multiple‐input single‐output Rayleigh‐fading channel in the presence of a multiple‐antenna eavesdropper – referred to as a multiple‐input single‐output multiple‐eavesdropper (MISOME) wiretap channel. Specifically, secure beamforming with artificial noise is treated when the transmitter has access to full channel state information (CSI) of a legitimate channel but only partial CSI of an eavesdropper channel. First, the optimal power allocation between the information‐bearing signal and artificial noise (or simulated interference) is derived to maximise the achievable secrecy rate in the presence of a weak or strong eavesdropper. Then, the first‐order optimal power allocation strategy is developed in a switched fashion by selecting the best of weak‐ and strong‐eavesdropper solutions for a general eavesdropping attack, and a closed‐form expression is derived for the ergodic secrecy rate achieved by secure beamforming with this switched power allocation in the MISOME wiretap channel. The numerical results show that the switched power allocation is a simple but effective approach that nearly achieves the optimal secrecy rate.
Design of improved Luby transform codes with decreasing ripple size and feedback
Authors: Zhang Lei , Liao Jianxin , Wang Jingyu , Li Tonghong , Qi Qi
Published: May 2014

In this study, the design of improved Luby transform codes with decreasing ripple size (LTC‐DRS) with feedback is presented. Under the proposed design, a new degree distribution algorithm named generalised degree distribution algorithm (GDDA) is proposed, which can achieve arbitrary ripple size revolution accurately. On the basis of GDDA, an accurate ripple size revolution based on binomial fitting is proposed, which can keep the ripple size to a suitable value throughout the decoding process. Furthermore, the authors introduce the feedback and propose a shifted ripple size revolution to diversify the degree values. The improved LTC‐DRS with feedback is evaluated and compared with the existing schemes. The simulation results demonstrate that it outperforms other existing schemes in terms of average overhead, average degree of encoded symbols, memory usage and energy consumption.
Enseignement de la microélectronique à Supélec :
une nouvelle pédagogie mise en place en 2012
Authors: Benabes Philippe , Lelandais-Perrault Caroline , Avignon Emilie , Roger Morgan , Bourgois Laurent , Vinci Filipe , Trélin Francis
Published: May 2014

La rentrée 2012 a été le cadre d’une réforme de l’enseignement de l’électronique intégrée au sein
de la majeure MNE (Micro et Nano Electronique) à Supélec. Les objectifs étaient de proposer une nouvelle
forme d’enseignement pratique au moyen d’un projet long, de regrouper un ensemble de cours dans un
ensemble cohérent, de faire intervenir tous les enseignants de l’équipe auprès des élèves dès la rentrée, et
surtout de proposer un maximum de pratique aux élèves de manière à remotiver les élèves autour d’une
discipline qui n’est pas toujours très à la mode dans le monde numérique actuel. L’évaluation des élèves a
aussi été repensée de manière à sortir les élèves d’un cadre scolaire et les mettre dans la peau d’un
responsable de projet au sein de l’industrie. L’introduction de points de passage formels avec remise de
rapports et présentation orale permet aux élèves de découvrir la réalité de leur métier de futur ingénieur. Le
retour des élèves a montré que ce nouvel enseignement a été très apprécié de l’ensemble des élèves.
Relativistic self-focusing of ultra-high intensity X-ray laser beams in warm quantum plasma with upward density profile
Authors: Habibi M. , Ghamari F.
Published: May 2014

The results of a numerical study of high-intensity X-ray laser beam interaction with warm quantum plasma (WQP) are presented. By means of an upward ramp density profile combined with quantum factors specially the Fermi velocity, we have demonstrated significant relativistic self-focusing (RSF) of a Gaussian electromagnetic beam in the WQP where the Fermi temperature term in the dielectric function is important. For this purpose, we have considered the quantum hydrodynamics model that modifies refractive index of inhomogeneous WQPs with the inclusion of quantum correction through the quantum statistical and diffraction effects in the relativistic regime. Also, to better illustration of the physical difference between warm and cold quantum plasmas and their effect on the RSF, we have derived the envelope equation governing the spot size of X-ray laser beam in Q-plasmas. In addition to the upward ramp density profile, we have found that the quantum effects would be caused much higher oscillation and better focusing of X-ray laser beam in the WQP compared to that of cold quantum case. Our computational results reveal the importance of the use of electrons density profile and Fermi speed in enhancing self-focusing of laser beam.
Adaptive fuzzy logic control based optimal Hopfield neural network of standalone photovoltaic system with battery storage
Authors: Arulmurugan R. , Suthanthiravanitha N.
Published: May 2014

This paper presents the optimized Hopfield Neural Network (HFNN) based Fuzzy Logic Control (FLC) Maximum Power Tracking structure for a renewable Photovoltaic (PV) system under changing climatic conditions. Changing climatic condition of photovoltaic panel yield multiple local and global maximum power points, which creates tracing of the extreme power which is a problematic task. Most of existing traditional techniques fail to operate accurately under this changing weather condition. This paper advances the technique by considering wide search and changing climate so that the designed HFNN trace the maximum power for the entire situation. It is verified for dissimilar weather condition through simulation and proved experimentally. In this paper, the major merit of using optimized new FLC is also presented. HFNN neurons are optimized using new FLC. Comparative tests have been conducted for conventional Perturb and Observe and Incremental Conductance methods. From the outcomes of the simulation results, it is measured that the HFNN technique decreases error and it contributes quick reaction to climatic variations. Moreover, it does not need any external fine-tuning of the structure, unlike existing traditional FLC technique, wherein the regulator gain components want to be altered when solar illumination varies.
Influence of plasma density on the chemical composition and structural properties of pulsed laser deposited TiAlN thin films
Authors: Quiñones-Galván J. G. , Camps Enrique , Muhl S. , Flores M. , Campos-González E.
Published: May 2014

Incorporation of substitutional Al into the TiN lattice of the ternary alloy TiAlN results in a material with improved properties compared to TiN. In this work, TiAlN thin films were grown by the simultaneous ablation of Ti and Al targets in a nitrogen containing reactive atmosphere. The deposit was formed on silicon substrates at low deposition temperature (200 °C). The dependence of the Al content of the films was studied as a function of the ion density of the plasma produced by the laser ablation of the Al target. The plasma parameters were measured by means of a planar Langmuir probe and optical emission spectroscopy. The chemical composition of the films was measured by energy dispersive X-ray spectroscopy. The results showed a strong dependence of the amount of aluminum incorporated in the films with the plasma density. The structural characterization of the deposits was carried out by Raman spectroscopy, X-ray diffraction, and transmission electron microscopy, where the substitutional incorporation of the Al into the TiN was demonstrated.
Note: Real-time absolute air refractometer
Authors: Huang Pei , Zhang Jitao , Li Yan , Wei Haoyun
Published: May 2014

We present a real-time absolute air refractometer benefiting from the synthetic pseudo-wavelength (SPW) method. Based on laser heterodyne interferometry, the SPW method uses three vacuum cells with specific lengths to synthesize a set of synthetic pseudo-wavelengths, by combination of which the refractive index can be determined directly without ambiguity. In addition, owing to the parallel arrangement of the vacuum cells in the optical path, the measured data can be collected simultaneously so that one measurement process can be less than 2 ms. The real-time feature makes it possible for instantaneous compensation for laser interferometers.
Ultraviolet laser crystallized ZnO:Al films on sapphire with high Hall mobility for simultaneous enhancement of conductivity and transparency
Authors: Nian Qiong , Zhang Martin Y. , Schwartz Bradley D. , Cheng Gary J.
Published: May 2014

One of the most challenging issues in transparent conductive oxides (TCOs) is to improve their conductivity without compromising transparency. High conductivity in TCO films often comes from a high carrier concentration, which is detrimental to transparency due to free carrier absorption. Here we show that UV laser crystallization (UVLC) of aluminum-doped ZnO (AZO) films prepared by pulsed laser deposition on sapphire results in much higher Hall mobility, allowing relaxation of the constraints of the conductivity/transparency trade-off. X-ray diffraction patterns and morphological characterizations show grain growth and crystallinity enhancement during UVLC, resulting in less film internal imperfections. Optoelectronic measurements show that UVLC dramatically improves the electron mobility, while the carrier concentration decreases which in turn simultaneously increases conductivity and transparency. AZO films under optimized UVLC achieve the highest electron mobility of 79 cm2/V s at a low carrier concentration of 7.9 × 10+19 cm−3. This is realized by a laser crystallization induced decrease of both grain boundary density and electron trap density at grain boundaries. The infrared (IR) to mid-IR range transmittance spectrum shows UVLC significantly enhances the AZO film transparency without compromising conductivity.
Coliphage HK022 Nun protein inhibits RNA polymerase translocation
Authors: Vitiello Christal L. , Kireeva Maria L. , Lubkowska Lucyna , Kashlev Mikhail , Gottesman Max
Published: May 2014

Significance

Gene expression can be regulated at the level of transcription elongation. Coliphage HK022 Nun protein suppresses coliphage λ development by inhibiting transcription elongation. We have determined the mechanism of Nun action in a purified in vitro transcription system. Nun blocks RNA polymerase (RNAP) lateral movement on the DNA template, thereby preventing translocation. Nun requires a 9- to 10-bp RNA–DNA hybrid and recognizes RNA or DNA sequences at the 5′ end of the hybrid. Suppression of lateral movement of RNAP represents a newly described regulatory mechanism.
Refining normative stakeholder theory: insights from Judaism, Christianity, and Islam
Authors: Ray Donna E. , Berman Shawn L. , Johnson-Cramer Michael E. , Van Buren Harry J.
Published: May 2014

Given the historical and ongoing influence of religion, religious faith traditions might provide a compelling and coherent normative core for stakeholder theory. This paper explores the three Abrahamic faith traditions – Judaism, Christianity, and Islam – and applies principles derived from these traditions to stakeholder theory. Our analysis of these faith traditions yields four elements of a common normative core that is germane to stakeholder theory: (1) the need to place community at the center of human activity, including business activity; (2) skepticism about economic power and its misapplication; (3) a tempering of our commitment to individual liberty as the highest normative good to be achieved by society; and (4) the dignity of the individual person and, with that, an obligation of reciprocity between the individual and society (including businesses). We then identify two current issues in stakeholder research, considering ways that the three faith traditions would advance discussion about them. We conclude by offering implications for future research.
Mythical Past and Historied Present: Another Interpretation of a Polychrome Vessel from Nochixtlan, Oaxaca
Authors: Urcid Javier
Published: May 2014

This study presents an alternative interpretation of one of the most aesthetically charged objects known from southwestern Mesoamerica, a tripod vessel seemingly manufactured in the fifteenth century CE. The analysis links the content of the visual narrative painted on the vessel with the use of the object, a function glyphically described around its neck. I argue that the binary structure of the depicted imagery and of the myth of origin encoded in the narrative was dialectically projected into the historical social field that motivated the commissioning of the artifact: a marital alliance to unite two powerful noble houses in order to forge a new dynasty. The deployment of the vessel to drink cacao during a marriage ceremony helps explain how its inscribed surface was meant to be read, and the depicted archetypical toponyms are hypothetically identified with lived places in the valleys of Nochixtlan and Coixtlahuaca.
Characterization of fractures and faults: a multi‐component passive microseismic study from the Ekofisk reservoir
Authors: Jones G.A. , Kendall J.‐M. , Bastow I. , Raymer D.G. , Wuestefeld A.
Published: May 2014

Fractures and faults within a reservoir can provide important pathways for the movement of reservoir fluids. Understanding the character and properties of these features on a range of length scales can be vital for the efficient exploitation of natural resources, whether it be enhanced oil and gas recovery, the safe storage of CO2, or better exploitation of geothermal heat. The monitoring of microseismicity within a reservoir illuminates active faults, but these events can be also used to characterize fracture networks through measurements of seismic anisotropy. In this study we use microseismic data acquired over an 18‐day period in April 1997 at the Ekofisk oil field in the North Sea. Using the analysis of seismic multiplets we delineate a number of sub‐vertical tectonic faults, which are consistent with previous core data analysis and seismic reflection work. We use shear wave splitting measurements, which are indicative of fracture‐induced seismic anisotropy, to infer the orientation of aligned aseismic fracture sets within the reservoir. The estimated fracture dip and strike from the shear wave splitting analysis are consistent with the active tectonic fractures characterized by the multiplets, but this analysis also illuminates spatial variations in fracture properties. Such monitoring on a longer term and with multiple wells is a promising tool for better understanding fracture and fault‐controlled flow within reservoirs.
National Academy of Sciences “Standardization”: On What Terms?
Authors: Bunch Ann W.
Published: May 2014

The frequently cited 2009 National Academy of Sciences Report entitled “Strengthening Forensic Science in the United States: A Path Forward” has become a focal point of forensic science practitioners' discussions and research since its publication. One of its recommendations is “Standardized Terminology and Reporting”. Little has been published to date on this topic, although conversations and dialogs on the subject are ongoing. The upshot of this communication is to draw attention to the problem of one term in particular, perimortem, which may be only the proverbial “tip of the iceberg” in the lexicon‐related concerns of forensic scientists. Even if it is an isolated issue, it is one that reflects the need for a consensus on term use and definitions by interdisciplinary practitioners who are currently using the term haphazardly, to the confusion of colleagues and potentially finders‐of‐fact in the courts.
Pyriproxyfen promotes lipid accumulation in 3T3‐L1 adipocytes by enhancement of TR4 activity
Authors: Choi Hojung , Kim Eungseok
Published: May 2014

Insect hormones and their synthetic analogs have been suggested to modulate gene expression in mammals. Thus, we investigated to determine the role of pyriproxyfen, a juvenile hormone (JH) analog, in the transcriptional activity of TR4, which functions as a key modulator of energy homeostasis. Here, we demonstrate that 100 μM pyriproxyfen enhances TR4 transcriptional activity with increase of expression of TR4 target genes such as FATP1 and PEPCK in 3T3‐L1 adipocytes. Furthermore, pyriproxyfen treatment resulted in increase of lipid accumulation during adipocyte differentiation of 3T3‐L1 cells. In reporter gene assays, pyriproxyfen promotes TR4 transactivation of the reporter genes linked to different target gene promoters. Knockdown of TR4 in 3T3‐L1 cells abolished promoting effect of 100 μM pyriproxyfen on lipid accumulation and expression of lipogenic genes, suggesting that pyriproxyfen may regulate adipogenesis of 3T3‐L1 cells via modulation of TR4 transcriptional activity. Together, our results suggest that pyriproxyfen, a JH analog, may modulate lipid homeostasis in adipocytes via regulation of TR4 activity.
Predicting walnut (Juglans spp.) crop yield using meteorological and airborne pollen data
Authors: Prentović M. , Radišić P. , Smith M. , Šikoparija B.
Published: May 2014

Crop yield determines economy by influencing prices on the trade market, and so accurate forecasts of the yield are important for planning various aspects of agricultural production. The main aim of this study is to construct a model for predicting walnut yield in an important walnut production area (the region of Novi Sad in Northern Serbia). Relationships between the amount of walnuts produced annually (2000–2011) and abiotic (e.g. meteorological) and biotic (e.g. airborne pollen data) factors were examined using Pearson correlation analysis. Walnut yield data were then entered into linear regression models with variables that had the highest correlations. The models were constructed using 10 years of data, and tested using 2 years of data not included in constructing the model. This paper has shown that walnut yield is greatly dependent on weather conditions, particularly during fertilisation and seed growth, but the amount of available airborne pollen also plays an important role. The introduction of the seasonal pollen index, as a proxy for the amount of pollen available for fertilisation, improved the performance of models predicting walnut yield.
Plasma profile of pro‐inflammatory cytokines and chemokines in cocaine users under outpatient treatment: influence of cocaine symptom severity and psychiatric co‐morbidity
Authors: Araos Pedro , Pedraz María , Serrano Antonia , Lucena Miguel , Barrios Vicente , García‐Marchena Nuria , Campos‐Cloute Rafael , Ruiz Juan J. , Romero Pablo , Suárez Juan , Baixeras Elena , de la Torre Rafael , Montesinos Jorge , Guerri Consuelo , Rodríguez‐Arias Marta , Miñarro José , Martínez‐Riera Roser , Torrens Marta , Chowen Julie A. , Argente Jesús , Mason Barbara J. , Pavón Francisco J. , Rodríguez de Fonseca Fernando
Published: May 2014

The treatment for cocaine use constitutes a clinical challenge because of the lack of appropriate therapies and the high rate of relapse. Recent evidence indicates that the immune system might be involved in the pathogenesis of cocaine addiction and its co‐morbid psychiatric disorders. This work examined the plasma pro‐inflammatory cytokine and chemokine profile in abstinent cocaine users (n = 82) who sought outpatient cocaine treatment and age/sex/body mass‐matched controls (n = 65). Participants were assessed with the diagnostic interview Psychiatric Research Interview for Substance and Mental Diseases according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM‐IV‐TR). Tumor necrosis factor‐alpha, chemokine (C‐C motif) ligand 2/monocyte chemotactic protein‐1 and chemokine (C‐X‐C motif) ligand 12 (CXCL12)/stromal cell‐derived factor‐1 (SDF‐1) were decreased in cocaine users, although all cytokines were identified as predictors of a lifetime pathological use of cocaine. Interleukin‐1 beta (IL‐1β), chemokine (C‐X3‐C motif) ligand 1 (CX3CL1)/fractalkine and CXCL12/SDF‐1 positively correlated with the cocaine symptom severity when using the DSM‐IV‐TR criteria for cocaine abuse/dependence. These cytokines allowed the categorization of the outpatients into subgroups according to severity, identifying a subgroup of severe cocaine users (9–11 criteria) with increased prevalence of co‐morbid psychiatric disorders [mood (54%), anxiety (32%), psychotic (30%) and personality (60%) disorders]. IL‐1β was observed to be increased in users with such psychiatric disorders relative to those users with no diagnosis. In addition to these clinical data, studies in mice demonstrated that plasma IL‐1β, CX3CL1 and CXCL12 were also affected after acute and chronic cocaine administration, providing a preclinical model for further research. In conclusion, cocaine exposure modifies the circulating levels of pro‐inflammatory mediators. Plasma cytokine/chemokine monitoring could improve the stratification of cocaine consumers seeking treatment and thus facilitate the application of appropriate interventions, including management of heightened risk of psychiatric co‐morbidity. Further research is necessary to elucidate the role of the immune system in the etiology of cocaine addiction.
Depression screening among older adults attending low‐vision rehabilitation and eye‐care services: Characteristics of those who screen positive and client acceptability of screening
Authors: Holloway Edith E. , Sturrock Bonnie A. , Lamoureux Ecosse L. , Keeffe Jill E. , Rees Gwyneth
Published: May 2014

Aim

To investigate characteristics associated with screening positive for depressive symptoms among older adults accessing low‐vision rehabilitation and eye‐care services and to determine client acceptability of depression screening using the Patient Health Questionnaire‐2 (PHQ‐2) in these settings.

Methods

One‐hundred and twenty‐four older adults (mean = 77.02 years, SD = 9.12) attending low‐vision rehabilitation and eye‐care services across Australia were screened for depression and invited to complete a telephone‐administered questionnaire to determine characteristics associated with depressive symptoms and client acceptability of screening in these settings.

Results

Thirty‐seven per cent (n = 46/124) of participants screened positive for depressive symptoms, and the majority considered the new depression screening method to be a ‘good idea’ in vision services (85%). Severe vision loss (<6/60 in the better eye) was associated with an increased odds of screening positive for depressive symptoms (odds ratio 2.37; 95% confidence interval 1.08–6.70) even after adjusting for potential confounders. Participants who screened positive had a preference for ‘talking’ therapy or a combination of medication and ‘talking therapy’ delivered within their own home (73%) or via telephone (67%).

Conclusion

The PHQ‐2 appears to be an acceptable method for depression screening in eye‐care settings among older adults. Targeted interventions that incorporate home‐based or telephone delivered therapy sessions may improve outcomes for depression in this group.
Effect of captopril on collagen metabolisms in keloid fibroblast cells
Authors: Chen Junjie , Zhao Sha , Liu Yong , Cen Ying , Nicolas Crook
Published: May 2014

Background

Keloid is a proliferative disease of fibrous tissues. The mechanism and consistently effective treatments of keloid remained unknown. Although there was a report about treating keloid with topical captopril, the further investigation about captopril affecting keloid has not been performed so far.

Objectives

The aim of this study was to analyse the effect of captopril on collagen metabolisms in keloid fibroblast cells, and to provide information for the mechanism and therapy of keloid.

Methods

To investigate the effects and relative mechanism of captopril on keloid fibroblast cells, we examined the changes of collagen metabolism, expression of angiotensin, transforming growth factor (TGF)‐β1, platelet‐derived growth factor (PDGF)‐BB and heat shock protein 47 (HSP47), and cellular proliferation in keloid fibroblast cells.

Results

We found that all collagen metabolisms, expression of TGF‐β1, PDGF‐BB and HSP47, and cellular proliferation decreased significantly with effective captopril concentrations in keloid fibroblast cells.

Conclusions

With a comprehensive analysis of test results, we proposed that captopril may decrease the expression of angiotensin, PDGF‐BB, TGF‐β1 and HSP47, and further inhibit proliferation and collagen synthesis of keloid fibroblast cells, which were the key in keloid formation.
USL255 extended‐release topiramate: Dose‐proportional pharmacokinetics and tolerability in healthy volunteers
Authors: Clark Annie M. , Halvorsen Mark B. , Braun Tricia L. , Johnson Krista M. , Cloyd James C.
Published: May 2014

Objective

Evaluate the pharmacokinetics (PK), safety, and tolerability of single doses of once‐daily USL255, Qudexy XR (topiramate) extended‐release capsules, over a wide dosing range.

Methods

Two single‐dose, phase I studies in healthy adults were used to evaluate the PK profile and maximum tolerated dose (MTD) of USL255 from 25–1,400 mg. Standard PK parameters assessed included area under the plasma concentration‐time curve (AUC) and maximum plasma concentration (Cmax). Dose proportionality, linearity, and intersubject and intrasubject variability (coefficient of variation [%CV]) of AUC and Cmax were evaluated. Investigator‐reported adverse events (AEs) were obtained throughout the studies.

Results

After the initial increase in plasma concentration levels immediately following administration of USL255 25–1,400 mg, plasma topiramate concentration‐time profiles were flat up to 24 h after dosing. AUC was dose proportional from 25–1,400 mg, and Cmax was dose proportional from 50–1,400 mg; both AUC and Cmax were linear across the entire dose range. Low intersubject and intrasubject %CV values were observed for AUC0−t, AUC0−∞, and Cmax (intersubject %CV: 20.2, 19.6, and 22.4%, respectively; intrasubject %CV of dose‐normalized mean values: 10.8, 8.2, and 13.2%, respectively). USL255 was generally safe and well tolerated with MTD established at 1,200 mg.

Significance

These results demonstrate that USL255 provides consistent plasma topiramate exposure across an extended‐dosing interval and predictable plasma topiramate concentrations over a wide dosing range. Overall, the favorable safety profile and consistency of exposure suggest once‐daily USL255 can be a useful treatment option for patients with epilepsy.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Antiepileptic activity of preferential inhibitors of persistent sodium current
Authors: Anderson Lyndsey L. , Thompson Christopher H. , Hawkins Nicole A. , Nath Ravi D. , Petersohn Adam A. , Rajamani Sridharan , Bush William S. , Frankel Wayne N. , Vanoye Carlos G. , Kearney Jennifer A. , George Alfred L.
Published: May 2014

Objective

Evidence from basic neurophysiology and molecular genetics has implicated persistent sodium current conducted by voltage‐gated sodium (NaV) channels as a contributor to the pathogenesis of epilepsy. Many antiepileptic drugs target NaV channels and modulate neuronal excitability, mainly by a use‐dependent block of transient sodium current, although suppression of persistent current may also contribute to the efficacy of these drugs. We hypothesized that a drug or compound capable of preferential inhibition of persistent sodium current would have antiepileptic activity.

Methods

We examined the antiepileptic activity of two selective persistent sodium current blockers ranolazine, a U.S. Food and Drug Administration (FDA)–approved drug for treatment of angina pectoris, and GS967, a novel compound with more potent effects on persistent current, in the epileptic Scn2aQ54 mouse model. We also examined the effect of GS967 in the maximal electroshock model and evaluated effects of the compound on neuronal excitability, propensity for hilar neuron loss, development of mossy fiber sprouting, and survival of Scn2aQ54 mice.

Results

We found that ranolazine was capable of reducing seizure frequency by approximately 50% in Scn2aQ54 mice. The more potent persistent current blocker GS967 reduced seizure frequency by >90% in Scn2aQ54 mice and protected against induced seizures in the maximal electroshock model. GS967 greatly attenuated abnormal spontaneous action potential firing in pyramidal neurons acutely isolated from Scn2aQ54 mice. In addition to seizure suppression in vivo, GS967 treatment greatly improved the survival of Scn2aQ54 mice, prevented hilar neuron loss, and suppressed the development of hippocampal mossy fiber sprouting.

Significance

Our findings indicate that the selective persistent sodium current blocker GS967 has potent antiepileptic activity and that this compound could inform development of new agents.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Helicobacter hepaticus Cholesterol‐α‐glucosyltransferase is Essential for Establishing Colonization in Male A/JCr Mice
Authors: Ge Zhongming , Feng Yan , Muthupalani Sureshkumar , Whary Mark T. , Versalovic James , Fox James G.
Published: May 2014

Background

Helicobacter pylori cholesterol‐α‐glucosyltransferase (cgt) is essential for survival of H. pylori in mice. Enterohepatic H. hepaticus, the cause of colonic and hepatocellular carcinoma in susceptible mouse strains, contains an ortholog of the H. pylori cgt. However, the role of cgt in the pathogenesis of H. hepaticus has not been investigated.

Materials and Methods

Two cgt‐deficient isogenic mutants of wild‐type H. hepaticus (WT) 3B1 were generated and used to inoculate male A/JCr mice. Cecal and hepatic colonization levels of the mutants and WT 3B1 as well as select inflammation‐associated cytokines were measured by qPCR at 4 months postinoculation.

Results

Both mutants were undetectable in the cecum of any inoculated mice (10 per mutant) but were detected in two livers (one for each mutant); by contrast, 9 and 7 of 10 mice inoculated with WT 3B1 were qPCR positive in the ceca and livers, respectively. The mice inoculated with the mutants developed significantly less severe hepatic inflammation (p < .05) and also produced significantly lower hepatic mRNA levels of proinflammatory cytokines Ifn‐γ (p < .01) and Tnf‐α (p ≤ .02) as well as anti‐inflammatory factors Il10 and Foxp3 compared with the WT 3B1‐inoculated mice. Additionally, the WT 3B1‐inoculated mice developed significantly higher Th1‐associated IgG2a (p < .0001) and Th2‐associated IgG1 responses (p < .0001) to H. hepaticus infection than mice dosed with isogenic cgt mutants.

Conclusion

Our data indicate that the cholesterol‐α‐glucosyltransferase is required for establishing colonization of the intestine and liver and therefore plays a critical role in the pathogenesis of H. hepaticus.
Impaired compensatory beta‐cell function and growth in response to high‐fat diet in LDL receptor knockout mice
Authors: Oliveira Ricardo B. d. , Carvalho Carolina P. d. F. , Polo Carla C. , Dorighello Gabriel d. G. , Boschero Antônio C. , Oliveira Helena C. F. d. , Collares‐Buzato Carla B.
Published: May 2014

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta‐cells in C57BL/6 mice fed a high‐fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild‐type (WT) and LDLr−/− mice were assessed. HF diet‐fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta‐cell secretory response to glucose. Overall, LDLr−/− mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose‐stimulated insulin secretion. HF diet induced similarly in WT and LDLr−/− mice, a significant decrease in Cx36 beta‐cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta‐cell mass mainly due to beta‐cell hypertrophy/replication. Nevertheless, HF diet‐fed LDLr−/− mice showed no significant changes in beta‐cell mass, but lower islet–duct association (neogenesis) and higher beta‐cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr−/− mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta‐cell expansion.
Chaetal loss and replacement in Pseudopotamilla reniformis (Sabellida, Annelida)
Authors: Kolbasova Glafira D. , Tzetlin Alexander B. , Kupriyanova Elena K.
Published: May 2014

Chaetae are continually being replaced during the life of a polychaete, but the process of chaetal degeneration during replacement is still poorly known. Chaetal loss occurs either one at a time through special degenerative sites, or all chaetae in a chaetal sac are lost simultaneously in the absence of degenerative sites. Old chaetae can be either resorbed inside the coelom or shed. This study describes chaetal degradation, loss, and subsequent replacement during experimentally induced regeneration in the sabellid polychaete Pseudopotamilla reniformis. During post‐traumatic regeneration in P. reniformis, abdominal‐type chaetae fall from the chaetal sac simultaneously without degenerative sites, and are replaced by thoracic‐type chaetae. Chaetal sac degradation occurs in three main stages: (1) formation of numerous lysosomes and small electron‐transparent vesicles in follicle cell cytoplasm; (2) disintegration of follicular cell membranes; and (3) disintegration of follicular cell cytoplasm. Description of changes during parapodial transformation allows identification of signs of degradation that can serve as histological indicators of chaetal degeneration in a wide range of polychaetes. Our study suggests that chaetal degeneration and loss in polychaetes can occur either with degenerative sites or without them, depending on the type of chaetal replacement.
Value of incisional negative pressure wound therapy in orthopaedic surgery
Authors: Brem Matthias H , Bail Hermann J , Biber Roland
Published: May 2014

Soft tissue and wound treatment after orthopaedic interventions (especially after trauma) is still an enormously challenging situation for every surgeon. Since development of negative pressure wound therapy (NPWT), new indications have been consistently added to the original field of application. Recently, NPWT has been applied directly over high‐risk closed surgical incisions. Review of the literature indicates that this therapy has shown positive effects on incisions after total ankle replacement or calcaneal fractures, preventing haematoma and wound dehiscence. In those cases reduced swelling, decreased pain and healing time of the wound were seen. Additionally, NPWT applied on incisions after acetabular fractures showed a decreased rate of infection and wound healing problems compared with published infection rates. Even after total hip arthroplasty, incisional NPWT reduced incidence of postoperative seroma and improved wound healing. In patients with tibial plateau, pilon or calcaneus fractures requiring surgical stabilisation after blunt trauma, reduced risk of developing acute and chronic wound dehiscence and infection was observed when using incisional NPWT. To conclude, incisional NPWT can help to reduce risk of delayed wound healing and infection after severe trauma and orthopaedic interventions.
Clinical Experience of Combined HeartWare Ventricular Assist Device and Implantable Cardioverter Defibrillator Therapy
Authors: PECHA SIMON , WILKE IRIS , BERNHARDT ALEXANDER , HAKMI SAMER , YILDIRIM YALIN , STEVEN DANIEL , REICHENSPURNER HERMANN , WILLEMS STEPHAN , DEUSE TOBIAS , AYDIN ALI
Published: May 2014

HeartWare Ventricular Assist Device and Implantable Cardioverter Defibrillator

Introduction

The HeartWare continuous flow ventricular assist device (HVAD) is used in an increasing number of heart failure patients. In those patients, ventricular arrhythmias (VAs) are common and, consequently, many patients already have an implanted implantable cardioverter defibrillator (ICD) in place or receive ICD implantation after left ventricular assist device implantation. However, limited data on feasibility and necessity of combined ICD and HVAD therapy are available. In this study we present our technical and clinical experience.

Methods and Results

Between 01/2010 and 06/2013, 41 patients received HVAD implantation. Twenty‐six HVAD patients who already had an ICD device placed prior to HVAD implantation or received ICD implantation afterwards were enrolled in this study. Peri‐ and postoperative complications as well as ICD interrogations were documented and analyzed retrospectively.

Mean patients age was 58.4 ± 12.6 years; 88.5% of patients were male. During mean follow‐up of 12.2 ± 8.9 months, appropriate ICD interventions occurred in 9 patients (34.6%) due to ventricular tachyarrhythmia (n = 7) or ventricular fibrillation (n = 2). An inappropriate ICD intervention was seen in 1 patient (3.9%) due to tachycardic atrial fibrillation. Patients on HVAD with a history of VAs (n = 13) had a significantly higher incidence of ICD interventions compared to patients with primary prophylactic indication for ICD (n = 13; 53.8% vs. 7.7%; P = 0.015). No disturbance of ICD function was seen after HVAD implantation.

Conclusion

Combined ICD and HVAD therapy was safe and feasible, without electromagnetic interference between ICD and ventricular assist device. The incidence of ICD interventions was high in patients with a history of VAs, but low in patients with ICD implantation for primary prevention.