bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Analysis of Well Logs and Seismic Data to Deduce the Possible Distribution in Depth of Gas Hydrate in Shenhu Area, South China Sea
Authors: Hua‐Ning XU , Guang‐Xue ZHANG , Xiao‐Dong ZHENG , Ming‐Jun WANG , Sheng‐Xiong YANG , Rui YANG , Bei‐Wen LIANG
Published: December 2014

The available geological and geophysical information indicates the presence of gas hydrate at Shenhu Area of Northern South China Sea. The drilling cores recovered in 2007 testify the expectation and reveal that the gas hydrate disseminates evenly within the hydrate stable zone (HSZ), but its regional distribution is inhomogeneous. However, the logging record length and coring depth coverage are limited, which causes the depth distribution of gas hydrate to be indeterminate. Logs at well site SH7 were used to link the information of physical properties of sediments to the coincident seismic data acquired in this area. According to the relation between physical properties of sediments and seismic reflection characteristics, three primary formations were calibrated and the pseudo‐well constrained impedance inversion was then applied on post‐stack seismic data. The results showed a high velocity zone below the interval bearing gas hydrate. To determine whether this high velocity zone is related to the occurrence of gas hydrate or not, the technique of AVO forward modeling was further used to analyze the reflecting characteristic of pre‐stack seismic data. The comparison between synthetic seismic models and real seismic data indicates that the HSZ was composed of thin interbeds of gas hydrate‐bearing sediments and water‐saturated sediments, which suggests that another gas hydrate deposit exists most likely below the depth where gas hydrate‐bearing sediments were cored in the hole.
Power allocation in the energy harvesting full‐duplex Gaussian relay channels
Authors: Feghhi Mahmood Mohassel , Mirmohseni Mahtab , Abbasfar Aliazam
Published: December 2014

In this paper, we propose a general model to study the full‐duplex non‐coherent (NC) decode‐and‐forward Gaussian relay channel (RC) with energy harvesting (EH) nodes, called NC‐EH‐
, in three cases: (i) no energy transfer (ET), (ii) one‐way ET from the source (S) to the relay (R), and (iii) two‐way ET. We consider the problem of optimal power allocation in NC‐EH‐
in order to maximize the total transmitted bits from S to the destination in a given time duration. General stochastic energy arrivals at S and R with known EH times and values are assumed. In NC‐EH‐
with no ET, the complicated min‐max optimization form along with its constraints make the problem intractable. It is shown that this problem can be transformed to a solvable convex form; however, convex optimization solution does not provide the structural properties of the optimal solution. Therefore, following an alternative perspective, we investigate conditions on harvesting process of S and R where we find optimal algorithmic solution. Further, we propose some suboptimal algorithms and provide some examples, in which the algorithms are optimal. Moreover, we find a class of problems for NC‐EH‐
with one‐way ET from S to R, where the optimal algorithmic solution is devised. For NC‐EH‐
with two‐way ET, we propose general optimal algorithmic solution. Furthermore, the performance of the proposed algorithms are evaluated numerically and compared with optimal numerical convex optimization tools. Copyright © 2014 John Wiley & Sons, Ltd.
Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome
Authors: Carsetti Rita , Valentini Diletta , Marcellini Valentina , Scarsella Marco , Marasco Emiliano , Giustini Ferruccio , Bartuli Andrea , Villani Alberto , Ugazio Alberto G.
Published: December 2014

Children with Down syndrome (DS) have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B‐cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B‐cell populations of 19 children with DS with those in healthy age‐matched controls. We found that all steps of peripheral B‐cell development are altered in DS, with a more severe defect during the later stages of B‐cell development. Transitional and mature‐naïve B‐cell numbers are reduced by 50% whereas switched memory B cells represent 10–15% of the numbers in age‐matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with DS have an increased ability to differentiate into antibody‐forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in DS.
Acetaminophen/paracetamol: A history of errors, failures and false decisions
Authors: Brune K. , Renner B. , Tiegs G.
Published: December 2014

Acetaminophen/paracetamol is the most widely used drug of the world. At the same time, it is probably one of the most dangerous compounds in medical use, causing hundreds of deaths in all industrialized countries due to acute liver failure (ALF). Publications of the last 130 years found in the usual databases were analyzed. Personal contacts existed to renowned researchers having contributed to the medical use of paracetamol and its precursors as H.U. Zollinger, S. Moeschlin, U. Dubach, J. Axelrod and others. Further information is found in earlier reviews by Eichengrün, Rodnan and Benedek, Sneader, Brune; comp. references. The history of the discovery of paracetamol starts with an error (active against worms), continues with a false assumption (paracetamol is safer than phenacetin), describes the first side‐effect ‘epidemy’ (phenacetin nephropathy, drug‐induced interstitial nephritis) and ends with the discovery of second‐generation problems due to the unavoidable production of a highly toxic metabolite of paracetamol N‐acetyl‐p‐benzoquinone imine (NAPQI) that may cause not only ALF and kidney damage but also impaired development of the fetus and the newborn child. It appears timely to reassess the risk/benefit ratio of this compound.
New results on the sum of Gamma random variates with application to the performance of wireless communication systems over Nakagami‐m fading channels
Authors: Ansari Imran Shafique , Yilmaz Ferkan , Alouini Mohamed‐Slim , Kucur Oğuz
Published: December 2014

The probability density function (PDF) and cumulative distribution function of the sum of L‐independent but not necessarily identically distributed Gamma variates, applicable to the output statistics of maximal ratio combining receiver operating over Nakagami‐m fading channels or in other words to the statistical analysis of the scenario where the sum of squared Nakagami‐m distributions is user‐of‐interest, are presented in closed form in terms of well‐known Meijer's G function and easily computable Fox's H̄ function for integer‐valued and non‐integer‐valued m fading parameters. Further analysis, particularly on bit error rate via a PDF‐based approach, is also offered in closed form in terms of Meijer's G function and Fox's H̄ function for integer‐valued fading parameters and extended Fox's H̄ function (
) for non‐integer‐valued fading parameters. Our proposed results complement previous known results that are either expressed in terms of infinite sums, nested sums or higher‐order derivatives of the fading parameter m. Copyright © 2014 John Wiley & Sons, Ltd.
Essential oil chemotypification and secretory structures of the neglected vegetable Smyrnium olusatrum L. (Apiaceae) growing in central Italy
Authors: Maggi Filippo , Papa Fabrizio , Giuliani Claudia , Maleci Bini Laura , Venditti Alessandro , Bianco Armandodoriano , Nicoletti Marcello , Iannarelli Romilde , Caprioli Giovanni , Sagratini Gianni , Cortese Manuela , Ricciutelli Massimo , Vittori Sauro
Published: December 2014

As part of our research on local plants, including neglected horticultural crops to be rediscovered as culinary vegetables, we focused on Smyrnium olusatrum, a biennal herb used in cuisine for many centuries by Romans that has now been replaced by celery. We investigated the essential oil compositions of different plant organs collected in 18 populations of central Italy (Marche, Umbria, Abruzzo, Tuscany and Latium) by gas chromatography (GC) with a flame ionization detector and GC with mass spectrometry (MS) to identify the main chemotypes that occur. Owing to the presence of thermosensitive molecules such as isofuranodiene, curzerene and germacrone undergoing Cope‐rearrangement during the GC run, a truthful quantitative determination of these constituents was accomplished by high‐performance liquid chromatography with a diode‐array detector (HPLC‐DAD). Chemical data were supported by a chemometric technique in the form of principal component analysis, which allowed identification of chemical differences among organs. Furanosesquiterpenoids were the main fraction of the oils, with isofuranodiene as the most abundant in flowers and roots, furanoeremophil‐1‐one in leaves and roots and 1‐β‐acetoxyfuranoeudesm‐4(15)‐ene in fruits. To complete the phytochemical analysis, polar compounds such as chlorogenic acid, isoquercitin, 3‐indoleacetic acid and saccharose were isolated from the ethanolic extracts of the plant by column chromatography and structurally elucidated by nuclear magnetic resonance. Moreover, a morphological and histochemical survey on the secretory structures was performed, with the special aim to localize the sites of terpenes biosynthesis in both above‐ and belowground organs. Overall, the results can be considered important in the light of the recent interest in neglected edible plants for botanical food supplements and functional foods market. Copyright © 2014 John Wiley & Sons, Ltd.
STIM1, STIM2, and Orai1 regulate store‐operated calcium entry and purinergic activation of microglia
Authors: Michaelis Marlen , Nieswandt Bernhard , Stegner David , Eilers Jens , Kraft Robert
Published: December 2014

Activation of microglia is the first and main immune response to brain injury. Release of the nucleotides ATP, ADP, and UDP from damaged cells regulate microglial migration and phagocytosis via purinergic P2Y receptors. We hypothesized that store‐operated Ca2+ entry (SOCE), the prevalent Ca2+ influx mechanism in non‐excitable cells, is a potent mediator of microglial responses to extracellular nucleotides. Expression analyses of STIM Ca2+ sensors and Orai Ca2+ channel subunits, that comprise the molecular machinery of SOCE, showed relevant levels of STIM1, STIM2, and Orai1 in cultured mouse microglia. STIM1 expression and SOCE were down‐regulated by treatment of microglia with lipopolysaccharide, suggesting that inflammation limits SOCE by lower STIM1 abundance. Ca2+ entry induced by cyclopiazonic acid, ATP, the P2Y6 receptor agonist UDP, or the P2Y12 receptor agonist 2‐methylthio‐ADP (2‐MeSADP) was clearly affected in microglia from Stim1–/–, Stim2–/–, and Orai1–/– mice. SOCE blockers or ablation of STIM1, STIM2, or Orai1 severely impaired nucleotide‐induced migration and phagocytosis in microglia. Thus, this study assigns SOCE, regulated by STIM1, STIM2, and Orai1 an essential role in purinergic signaling and activation of microglia. GLIA 2015;63:652–663
Microglial K+ channel expression in young adult and aged mice
Authors: Schilling Tom , Eder Claudia
Published: December 2014

The K+ channel expression pattern of microglia strongly depends on the cells' microenvironment and has been recognized as a sensitive marker of the cells' functional state. While numerous studies have been performed on microglia in vitro, our knowledge about microglial K+ channels and their regulation in vivo is limited. Here, we have investigated K+ currents of microglia in striatum, neocortex and entorhinal cortex of young adult and aged mice. Although almost all microglial cells exhibited inward rectifier K+ currents upon membrane hyperpolarization, their mean current density was significantly enhanced in aged mice compared with that determined in young adult mice. Some microglial cells additionally exhibited outward rectifier K+ currents in response to depolarizing voltage pulses. In aged mice, microglial outward rectifier K+ current density was significantly larger than in young adult mice due to the increased number of aged microglial cells expressing these channels. Aged dystrophic microglia exhibited outward rectifier K+ currents more frequently than aged ramified microglia. The majority of microglial cells expressed functional BK‐type, but not IK‐ or SK‐type, Ca2+‐activated K+ channels, while no differences were found in their expression levels between microglia of young adult and aged mice. Neither microglial K+ channel pattern nor K+ channel expression levels differed markedly between the three brain regions investigated. It is concluded that age‐related changes in microglial phenotype are accompanied by changes in the expression of microglial voltage‐activated, but not Ca2+‐activated, K+ channels. GLIA 2015;63:664–672
Novel CLC3 transcript variants in blood eosinophils and increased CLC3 expression in nasal lavage and blood eosinophils of asthmatics
Authors: Gaurav Rohit , Bewtra Againdra K. , Agrawal Devendra K.
Published: December 2014

Eosinophilia is a characteristic feature of allergic airway inflammation and remodeling. Chloride channel‐3 (CLC3) in eosinophils has been associated with superoxide generation and respiratory burst. The CLC3 gene may produce multiple transcript variants through alternative splicing. However, the presence of CLC3 variants in human eosinophils is unknown. We examined the expression of CLC3 transcript variants in peripheral blood eosinophils of allergic asthmatics and healthy individuals. Potential of these obligatory dimers to form homo‐ or hetero‐dimers was examined in HEK293 cells co‐transfected with CLC3b‐GFP and CLC3e‐RFP. Eosinophils were isolated from peripheral blood by negative selection. Expression of CLC3 and CLC3 transcript variants was examined by qPCR, Western blot, and immunofluorescence. Confocal micrographs were analyzed with Image J software. Higher levels of novel transcript variants of CLC3 (CLC3b and CLC3e) were found in peripheral blood eosinophils of asthmatics compared to healthy non‐atopic subjects. We also found higher CLC3 protein expression in the blood and nasal lavage eosinophils of asthmatics than healthy subjects. Both membranous and intracellular CLC3 expression were observed. Also, we found the presence of both homodimers and heterodimers of CLC3b‐GFP and CLC3e‐RFP in HEK293 cells. Higher and differential expression of novel CLC3 transcript variants in mild‐to‐moderate and moderate‐to‐severe asthmatic eosinophils suggest their critical role in allergic asthma. Membranous and intracellular (granular) expression of CLC3 in nasal lavage and peripheral blood eosinophils suggest their involvement in the activation and migration of eosinophils in allergic asthma. Moreover, homo‐ and hetero‐dimerization of these transcript variants may change the channel properties to exhibit these states. Presence of CLC3 variants may serve as a biomarker in allergic asthma and additional knowledge of interaction between CLC3 transcript variants and their specific role in the activation and migration of eosinophils will allow to explore novel therapeutic approach in allergic asthma.
Long‐term risk of cervical intraepithelial neoplasia grade 3 or worse according to high‐risk human papillomavirus genotype and semi‐quantitative viral load among 33,288 women with normal cervical cytology
Authors: Thomsen Louise T. , Frederiksen Kirsten , Munk Christian , Junge Jette , Iftner Thomas , Kjaer Susanne K.
Published: December 2014

In this prospective cohort study, we estimated the long‐term risk of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) by high‐risk human papillomavirus (hrHPV) genotype and semi‐quantitative viral load at baseline among 33,288 women aged 14–90 years with normal baseline cytology. During 2002–2005, residual liquid‐based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV‐tested with Hybrid Capture 2 (HC2) and genotyped with INNO‐LiPA. Semi‐quantitative viral load was measured by HC2 relative light units in women with single hrHPV infections. The cohort was followed in a nationwide pathology register for up to 11.5 years. In women aged ≥30 years at baseline, the 8‐year absolute risk for CIN3+ following baseline detection of HPV16 was 21.8% (95% confidence interval [CI]: 18.0–25.6%). The corresponding risks for HPV18, HPV31, HPV33, and other hrHPV types, respectively, were 12.8% (95% CI: 7.6–18.0%), 11.3% (95% CI: 7.7–14.9%), 12.9% (95% CI: 7.0–18.8%) and 3.9% (95% CI: 2.7–5.2%). Similar absolute risk estimates were observed in women aged <30 years. Higher HPV16‐viral load was associated with increased risk of CIN3+ (hazard ratio = 1.34, 95% CI: 1.10–1.64, per 10‐fold increase in viral load). A similar trend, although statistically nonsignificant, was found for viral load of HPV18. The 8‐year absolute risk of CIN3+ in women with HPV16‐viral load ≥100.0 pg/ml was 30.2% (95% CI: 21.9–38.6%). Our results support that hrHPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+.
A positive genotype–phenotype correlation in a large cohort of patients with Pseudohypoparathyroidism Type Ia and Pseudo‐pseudohypoparathyroidism and 33 newly identified mutations in the GNAS gene
Authors: Thiele Susanne , Werner Ralf , Grötzinger Joachim , Brix Bettina , Staedt Pia , Struve Dagmar , Reiz Benedikt , Farida Jennane , Hiort Olaf
Published: December 2014

Maternally inherited inactivating GNAS mutations are the most common cause of parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO) leading to pseudohypoparathyroidism type Ia (PHPIa) due to Gsα deficiency. Paternally inherited inactivating mutations lead to isolated AHO signs characterizing pseudo‐pseudohypoparathyroidism (PPHP). Mutations are distributed throughout the Gsα coding exons of GNAS and there is a lack of genotype–phenotype correlation. In this study, we sequenced exon 1–13 of GNAS in a large cohort of PHPIa‐ and PPHP patients and identified 58 different mutations in 88 patients and 27 relatives. Thirty‐three mutations including 15 missense mutations were newly discovered. Furthermore, we found three hot spots: a known hotspot (p.D190MfsX14), a second at codon 166 (p.R166C), and a third at the exon 5 acceptor splice site (c.435 + 1G>A), found in 15, 5, and 4 unrelated patients, respectively. Comparing the clinical features to the molecular genetic data, a significantly higher occurrence of subcutaneous calcifications in patients harboring truncating versus missense mutations was demonstrated. Thus, in the largest cohort of PHPIa patients described to date, we extend the spectrum of known GNAS mutations and hot spots and demonstrate for the first time a correlation between the genetic defects and the expression of a clinical AHO‐feature.
A branch‐and‐cut algorithm for the multi‐vehicle traveling purchaser problem with pairwise incompatibility constraints
Authors: Manerba Daniele , Mansini Renata
Published: December 2014

We introduce a problem where a fleet of vehicles is available to visit suppliers offering various products at different prices and quantities, with the aim to select a subset of suppliers so to satisfy products demand at the minimum traveling and purchasing costs. Vehicles have a predefined capacity and pairs of products may be incompatible to be carried simultaneously on a same vehicle. We call this problem the multi‐vehicle traveling purchaser problem with pairwise incompatibility constraints. We show how a three‐index one‐commodity flow formulation for the problem is easy to implement with a common MILP solver, but highly nonefficient when solving large size instances. We concentrate on a formulation using connectivity constraints to exclude subtours and introduce a branch‐and‐cut framework using a preprocessing routine and the separation of different valid inequalities. We also propose a four‐step heuristic based on the solution of different subproblems and use it to provide an initial feasible solution. We run computational tests on a large set of instances with up to 50 suppliers, 100 products, and 20% of crossed incompatibility between products. Results show that two different streamlined versions of the proposed exact method largely outperform the plain solution by the commercial solver Cplex 12.3. Also, the heuristic approach is observed to be rather effective and efficient providing a valid solving alternative. © 2014 Wiley Periodicals, Inc. NETWORKS, Vol. 65(2), 139–154 2015
Polymers in gene therapy technology
Authors: Hosseinkhani Hossein , Abedini Fatemeh , Ou Keng‐Liang , Domb Abraham J.
Published: December 2014

There are several barriers to gene delivery. One of the biggest challenges is the design of appropriate vectors. Currently, nonviral vectors have received significant attention because of low toxicity, potential for tissue specificity, stability during storage, lack of immunogenicity, and relatively low production cost. Despite the high efficiency of viral vectors, they show limited clinical applications because of potentially fatal adverse effects and because of the likelihood of the immune response shutting down the transgene expression system. Nonviral technologies comprise plasmid‐based expression systems harboring a gene that encodes a therapeutic protein along with a synthetic gene delivery system. This review provides a broad perspective on recent improvements in the development of four kinds of nonviral vectors that are based on polymers, peptides, lipids, and DNA and discusses the cytotoxicity associated with gene therapy. Copyright © 2014 John Wiley & Sons, Ltd.
Bone substitute of poly(amino acid)/β‐Ca2SiO4 biocomposite: Degradability and bioactivity
Authors: Wang Jie , Li Hong , Fan Xiaoxia , Li Tianwei , Lv Guoyu , Yan Yonggang
Published: December 2014

A poly(amino acid)/β‐Ca2SiO4(PAA/β‐Ca2SiO4) bioactive composite was prepared by in situ melting polymerization. The composition, structure, and morphology were characterized by infrared spectrometry, X‐ray diffraction, X‐ray photoelectron spectroscopy, scanning electron microscopy, and differential scanning calorimeter. The results indicated that the β‐Ca2SiO4 particles were uniformly distributed in the PAA matrix and some interaction was found at the interface between PAA and β‐Ca2SiO4. The crystallinity of PAA in the composite was found decreasing with the increase of β‐Ca2SiO4 content. The bioactivity of the composite was evaluated by soaking the composite in simulated body fluid (SBF) and results showed that the PAA/β‐Ca2SiO4 composite (PSC) could induce a dense and continuous layer of apatite after soaking for 1 week. In addition, the PSC was soaked SBF for 2 months, and the weight loss reached 8.77%, showing the composite could be degradable. Collectively, these results suggested that the incorporation of β‐Ca2SiO4 produced a biocomposite with enhanced bioactivity and might have potential applications as a bone tissue substitute. POLYM. COMPOS., 37:1335–1341, 2016. © 2014 Society of Plastics Engineers
Balance of Academic Responsibilities of Clinical Track Pharmacy Faculty in the United States: A Survey of Select American College of Clinical Pharmacy Practice and Research Network Members
Authors: Nutescu Edith A. , Engle Janet P. , Bathija Sacheeta , Grim Shellee A. , Chan Juliana , Mucksavage Jeffrey J. , Ohler Kirsten H. , Tesoro Eljim P. , Thielke James J. , Shapiro Nancy L. , Donnelly Andrew J. , Garofalo John , DiDomenico Robert J.
Published: December 2014

Study Objectives

To characterize the balance of clinical and academic responsibilities of clinical track pharmacy faculty in the United States and evaluate organizational structures that promote satisfactory balance between these responsibilities.

Design

Prospective cross‐sectional survey.

Setting

A 22‐item online survey was developed and distributed via Qualtrics software.

Participants

Clinical faculty members of the American College of Clinical Pharmacy Adult Medicine, Ambulatory Care, Cardiology, Critical Care, Gastrointestinal/Liver/Nutrition, Immunology/Transplantation, Infectious Disease, and Pediatrics Practice and Research Networks (PRNs) were invited to participate via the PRN electronic mailing list.

Measurements and Main Results

The survey comprised questions related to demographics, organizational structure, and balance of clinical and academic responsibilities. A total of 344 participants responded to some or all of the survey questions. The demographics were relatively equally balanced between faculty at state and private academic institutions, academic rank, and practice setting. Expected and actual effort allocations were similar for each of the clinical and academic responsibilities, with direct patient care and clinical teaching representing more than 50% effort allocation cumulatively. Clinical faculty at state institutions devoted a larger proportion of time to clinical service, whereas clinical faculty at private institutions devoted a greater proportion of time to didactic teaching. When asked about time constraints, 157 (69.8%) of the 225 survey participants responding to this question did not believe they had sufficient time to fulfill their nonclinical academic needs. Clinical faculty who were provided “protected time” away from clinical service had a significantly more favorable opinion of this question.

Conclusion

Most of the clinical track pharmacy faculty indicated that they have insufficient time to fulfill their nonclinical academic responsibilities. Provision of protected time may alleviate some of these time constraints.
Successful Use of Tetrabenazine in a Patient with Intractable Hiccups After Stroke
Authors: Naro Antonino , Bramanti Placido , Calabrò Rocco Salvatore
Published: December 2014

A hiccup is a myoclonic jerk of the diaphragm, and cases of hiccups may last for more than 48 hours (persistent hiccups) or even more than 2 months (intractable hiccups). Current pharmacologic treatment of persistent or intractable hiccups mainly includes antidopaminergic drugs. We describe the case of a 60‐year‐old man with a recent diagnosis of right insular ischemic stroke who presented with frequent, intense, and disabling hiccups for more than 1 month. As diagnosis of poststroke hiccups was assumed, the patient was treated over the next 6 months with adequate doses of various antipsychotic drugs commonly used for the treatment of hiccups; however, all were discontinued because of adverse effects. Indeed, dyskinesia after chlorpromazine (up to 75 mg/day for 4 wks), as well as somnolence and dyskinesia after haloperidol (up to 6 mg/day for 6 wks), somnolence after gabapentin (up to 1800 mg/day for 8 wks), and severe somnolence and hypotension after baclofen (up to 50 mg/day for 6 wks) were reported. The patient was then prescribed tetrabenazine at a starting dose of 12.5 mg twice/day (25 mg/day), with a nearly complete remission of the hiccup symptomatology after ~6 weeks, when a daily dose of 150 mg was reached. We therefore hypothesize that a supratentorial lesion may disrupt the modulation of dopaminergic pathways involved in the regulation of medullar centers responsible for the hiccup reflex. To our knowledge, this is the first case report of poststroke hiccups responding to tetrabenazine. The dramatic response of our patient to tetrabenazine monotherapy suggests that this drug may be a valuable pharmacologic alternative for patients with hiccups after stroke who are intolerant or unresponsive to classic antipsychotic agents.
Intraluminal proteome and peptidome of human urinary extracellular vesicles
Authors: Liu Xinyu , Chinello Clizia , Musante Luca , Cazzaniga Marta , Tataruch Dorota , Calzaferri Giulio , James Smith Andrew , De Sio Gabriele , Magni Fulvio , Zou Hequn , Holthofer Harry
Published: December 2014

Purpose

Urinary extracellular vesicles (UEVs) are a novel source for disease biomarker discovery. However, Tamm–Horsfall protein (THP) is still a challenge for proteomic analysis since it can inhibit detection of low‐abundance proteins. Here, we introduce a new approach that does not involve an ultracentrifugation step to enrich vesicles and that reduces the amount of THP to manageable levels.

Experimental design

UEVs were dialyzed and ultrafiltered after reduction and alkylation. The retained fraction was digested with trypsin to reduce the remaining THP and incubated with deoxycholate (DOC). The internal peptidome and internal proteome were analyzed by LC‐ESI‐MS.

Results

A total of 942 different proteins and 3115 unique endogenous peptide fragments deriving from 973 different protein isoforms were identified. Around 82% of the key endosomal sorting complex required for transport components of UEVs generation could be detected from the intraluminal content.

Conclusions and clinical relevance

Our UEVs preparation protocol provides a simplified way to investigate the intraluminal proteome and peptidome, in particular the subpopulation of UEVs of the trypsin‐resistant class of exosomes (positive for tumor susceptibility gene101) and eliminates the majority of interfering proteins such as THP. This method allows the possibility to study endoproteome and endopeptidome of UEVs, thus greatly facilitating biomarker discovery.
Immunological detection of glutamyl aminopeptidase in urine samples from cisplatin‐treated rats
Authors: Montoro‐Molina Sebastián , Quesada Andrés , Zafra‐Ruiz Piedad V. , O'Valle Francisco , Vargas Félix , de Gracia María del Carmen , Osuna Antonio , Wangensteen Rosemary
Published: December 2014

Purpose

The aim of this work is to demonstrate if urinary excretion of glutamyl aminopeptidase (GluAp) can be quantified by immunological methods.

Experimental design

Urine samples from control and cisplatin‐treated rats (n = 10 each group) were obtained at 1, 8, and 15 days after cisplatin injection. GluAp was analyzed by kinetic fluorimetry, ELISA, and immunoblotting. Sensitivity and specificity was studied for fluorimetric activity and ELISA 24 h after cisplatin injection. We also analyzed the predictive value over renal dysfunction at the end of the experiment.

Results

GluAp was easily detected by immunoblotting and ELISA, and its urinary excretion was increased in cisplatin‐treated rats (p < 0.01). Results obtained with ELISA were strongly correlated (r = 0.8186; p < 0.0001) with fluorimetric activity. Kinetic fluorimetry was the method with the highest AUC (AUC = 1) and the highest predictive value over serum creatinine (r = 0.7630; p = 0.0001) and body weight increase (r = –0.8721; p < 0.0001).

Conclusions and clinical relevance

GluAp can be detected in urine samples with immunological methods, making possible the development of an antibody‐based kit for its determination. Its excretion correlates with the extent of renal dysfunction in cisplatin‐treated rats, confirming its value as an early marker of renal damage that can be a diagnostic aid in renal diseases.
Thermal behaviour of wheat starch and flour at different water levels: Effect of pectins, modified celluloses and NaCl
Authors: Correa María J. , Ferrero Cristina
Published: December 2014

Rapid viscoanalyser (RVA) and differential scanning calorimetry (DSC) can be applied to study thermal transitions in starch based systems at different water levels. The effect of different hydrocolloids on wheat starch thermal transitions in the presence and absence of NaCl (2%) was evaluated in flour–hydrocolloid suspensions, starch–hydrocolloid mixtures and dough. These hydrocolloids include microcrystalline cellulose (MCC), carboxymethyl cellulose (CMC), two types of hydroxypropylmethylcellulose (HPMC F 4 M and F50), a low methoxyl pectin (LMP) and a high methoxyl pectin (HMP). The suspensions were submitted to a heating/cooling cycle in an RVA and a DSC was used to evaluate gelatinization and ALC transition in dough and mixtures. All of the suspensions containing NaCl exhibited higher hot paste stability. Furthermore, CMC and pectins showed an inhibitory effect on amylose retrogradation. Results also showed that starch thermal transitions in limited and excess water can be highly affected by hydrocolloids, particularly when NaCl is present.
Chemistry of Sumanene
Authors: Amaya Toru , Hirao Toshikazu
Published: December 2014

Sumanene (C21H12) is a bowl‐shaped π‐conjugated molecule with C3v symmetry, consisting of alternating benzene rings and cyclopentadiene rings around the central benzene ring. The structure corresponds to the smallest C3v‐symmetric fragment for the structural motifs of fullerenes or end‐caps of carbon nanotubes. The presence of three sp3‐hybridized benzylic sites is one of the most characteristic structural features in sumanene, which allows the different chemistry from that of corannulene. Since our first synthesis in 2003, we have engaged in the study of sumanene. This article summarizes our continuous study, including the synthesis, structure, dynamics, derivatization, complexation with transition metals, charge carrier mobility, and conversion to nitrogen‐doped graphitic carbon, of sumanene.
The neurotoxicity of amphetamines during the adolescent period
Authors: Teixeira‐Gomes Armanda , Costa Vera Marisa , Feio‐Azevedo Rita , Bastos Maria de Lourdes , Carvalho Félix , Capela João Paulo
Published: December 2014

Amphetamine‐type psychostimulants (ATS), such as amphetamine (AMPH), 3,4‐methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) are psychoactive substances widely abused, due to their powerful central nervous system (CNS) stimulation ability. Young people particularly use ATS as recreational drugs. Moreover, AMPH is used clinically, particularly for attention deficit hyperactivity disorder, and has the ability to cause structural and functional brain alterations. ATS are known to interact with monoamine transporter sites and easily diffuse across cellular membranes, attaining high levels in several tissues, particularly the brain. Strong evidence suggests that ATS induce neurotoxic effects, raising concerns about the consequences of drug abuse.

Considering that many teenagers and young adults commonly use ATS, our main aim was to review the neurotoxic effects of amphetamines, namely AMPH, MDMA, and METH, in the adolescence period of experimental animals. Reports agree that adolescent animals are less susceptible than adult animals to the neurotoxic effects of amphetamines. The susceptibility to the neurotoxic effects of ATS seems roughly located in the early adolescent period of animals. Many authors report that the age of exposure to ATS is crucial for the neurotoxic outcome, showing that the stage of brain maturity has a strong importance. Moreover, recent studies have been undertaken in young adults and/or consumers during adolescence that clearly indicate brain or behavioural damage, arguing for long‐term neurotoxic effects in humans. There is an urgent need for more studies during the adolescence period, in order to unveil the mechanisms and the brain dysfunctions promoted by ATS.
Efficacy of exogenous xylanases for improvingin vitrofermentation of forages
Authors: HE Z. X. , YANG L. Y. , YANG W. Z. , BEAUCHEMIN K. A. , TANG S. X. , HUANG J. Y. , ZHOU C. S. , HAN X. F. , WANG M. , KANG J. H. , ODONGO N. E. , TAN Z. L.
Published: December 2014

Batch cultures of mixed rumen micro-organisms were used to evaluate varying enzyme products with high xylanase activity (EPX), four of which were recombinant single xylanase activity developmental enzyme products (EPX1–EPX4, products of xylanase genes derived fromTrichoderma harzianum, Trichoderma reesei, OrpinomycesandAspergillus oryzae, respectively), for their potential to improvein vitroruminal fermentation of three forages [maize (Zea mays) stover (MS), rice (Oryza sativa) straw (RS) and Guimu No. 1 grass (Pennisetum americanum×Pennisetum purpureum, GM)]. The enzyme product EPX5, derived fromTrichoderma longibrachiatum, was used as a positive control that could improvein vitrofermentation of forages. Enzymes were supplied at dose rates of 0 (control), 20 (low), 50 (medium) and 80 (high) enzymic units of xylanase/g of dry matter (DM). There were no interactions between EPX and dose for the fermentation characteristics evaluated. Increasing EPX dose linearly increased gas production (GP) kinetic characters [i.e. asymptotic GP (VF), half time when GP is half of the theoretical maximum GP (t0·5), and initial fractional rate of degradation (FRD0)] and methane (CH4) production from RS and GM at 24 h, and increased degradability of DM at 24 h for MS and RS. A linear increase in degradability of neutral detergent fibre (NDF) of the three forages at 24 h was observed with increasing dose of EPX, but at 48 h only NDF degradability of RS was increased. There were differences in the effects of EPX on degradability of DM and NDF from RS at 24 h, with EPX4 having the highest and EPX1 having the lowest. In addition, increasing EPX dose linearly increased acetate proportion at 24 h and total volatile fatty acids (TVFA) at 48 h in MS. Increasing EPX dose linearly increased TVFA at 24 h, and ammonia-nitrogen (NH3-N) concentration at 48 h in RS. For GM, linear or quadratic effects of dose on acetate and butyrate concentration were observed at 24 and 48 h. The present study indicates that applying EPX to low-quality forages has the potential to improve rumen degradability and utilization. Furthermore, EPX from different sources differed in their effects when applied at the same dose rate, with the responses being forage-specific. For RS, the EPX derived fromA. oryzaeshowed the greatest positive effects on forage degradation; whereas for MS and GM, the source of micro-organism where EPX gene was derived did not affect the degradation, with little difference among the EPX evaluated.
Superbanana and superbanana plateau transport in finite aspect ratio tokamaks with broken symmetry
Authors: Shaing K. C.
Published: December 2014

Superbanana and superbanana plateau transport processes are critical to plasma confinement in tokamaks with broken symmetry. The transport is caused by the superbanana resonance, which occurs at a pitch angle that makes the toroidal drift speed vanish, i.e. the tips of the superbananas. The physics consequences of the resonance on the symmetry breaking induced toroidal momentum damping and on the energetic alpha particle transport have been demonstrated using large aspect ratio expansion. Here, the existing theory for the superbanana and superbanana plateau transport is extended for finite aspect ratio tokamaks with broken symmetry. The effects of finite plasma β, and magnetic field shear are naturally included. Here, β is the ratio of the thermal plasma pressure to the magnetic field pressure. The explicit expressions for the transport fluxes in these regimes in terms of the equilibrium quantities are presented. It is shown that the main effects are to modify the resonance function G(k) and the expression for the pitch angle parameter k in the existing theory.
Impact of the cestodeTriaenophorus nodulosuson the exoticLepomis gibbosusand the autochthonousPerca fluviatilis
Authors: MASSON G. , VANACKER M. , FOX M. G. , BEISEL J.-N.
Published: December 2014

The effects of plerocercoids of the cestodeTriaenophorus nodulosusinfecting the livers of native Eurasian perchPerca fluviatilisand non-native pumpkinseedLepomis gibbosuswas investigated in 17 sites along the Moselle watershed. With a single exception, infected individuals were not observed in the main channel whether or not northern pikeEsox lucius, a final host, was present. In ponds where the pike was present, the prevalence ofT. nodulosusaveraged 86% in Eurasian perch and 15% in pumpkinseed. The parasite was not present at all in ponds when pike were absent. Parasite load, hepatosomatic index (HSI), gonadosomatic index (GSI) and body condition index (CI) were compared between hosts in one site where parasite prevalence and fish abundance was highest. HSI in infected perch was significantly higher than in uninfected perch, whereas no differences in HSI were detected between infected and uninfected pumpkinseed. While perch were more frequently infected and had a greater average parasite load than pumpkinseed, there were no significant differences in either indicator between the two species. Furthermore, no significant differences in GSI or CI were observed between infected and uninfected fish in either species, by either gender or maturity stage. We hypothesize that pumpkinseed is more resistant to the parasite or less likely to feed upon infected copepods than perch.
Smartphone Shadow Matching for Better Cross-street GNSS Positioning in Urban Environments
Authors: Wang Lei , Groves Paul D , Ziebart Marek K
Published: December 2014

Global Navigation Satellite System (GNSS) shadow matching is a new positioning technique that determines position by comparing the measured signal availability and strength with predictions made using a three-dimensional (3D) city model. It complements conventional GNSS positioning and can significantly improve cross-street positioning accuracy in dense urban environments. This paper describes how shadow matching has been adapted to work on an Android smartphone and presents the first comprehensive performance assessment of smartphone GNSS shadow matching. Using GPS and GLONASS data recorded at 20 locations within central London, it is shown that shadow matching significantly outperforms conventional GNSS positioning in the cross-street direction. The success rate for obtaining a cross-street position accuracy within 5 m, enabling the correct side of a street to be determined, was 54·50% using shadow matching, compared to 24·77% for the conventional GNSS position. The likely performance of four-constellation shadow matching is predicted, the feasibility of a large-scale implementation of shadow matching is assessed, and some methods for improving performance are proposed. A further contribution is a signal-to-noise ratio analysis of the direct line-of-sight and non-line-of-sight signals received on a smartphone in a dense urban environment.
Optimising the attractiveness of winter oilseed rape fields as foraging habitat for the West Pannonian Great BustardOtis tardapopulation during winter
Authors: RAAB RAINER , SCHÜTZ CLAUDIA , SPAKOVSZKY PÉTER , JULIUS EIKE , SCHULZE CHRISTIAN H.
Published: December 2014

Winter oilseed rape represents an important food source for Great Bustards. Great Bustard surveys during four consecutive winters (2005/2006–2008/2009) were used to identify characteristics of oilseed rape fields, which increase their attractiveness for the species in its West Pannonian wintering area. The study was conducted in study areas in Eastern Austria, around the Austrian–Slovakian–Hungarian border and in the Hungarian Moson Plain. To test for effects of field size and isolation of fields from other rape fields, and the distance to the nearest paved road on occurrence and abundance of Great Bustards (maximum number of birds counted in individual rape fields per winter), we calculated generalized linear mixed models (GLMMs) including all three predictor variables as fixed effects and winter as random effect for each of the three study areas. Field size most strongly affected occurrence and abundance of Great Bustards. The availability of large (>>15 ha) winter rape fields far from paved roads is recommended as a prime conservation measure to improve the quality of rape fields as foraging habitat for Great Bustards during the winter months (November–March).
Modules over relative monads for syntax and semantics
Authors: AHRENS BENEDIKT
Published: December 2014

We give an algebraic characterization of the syntax and semantics of a class of untyped functional programming languages.

To this end, we introduce a notion of 2-signature: such a signature specifies not only the terms of a language, but also reduction rules on those terms. To any 2-signature (S, A) we associate a category of ‘models’. We then prove that this category has an initial object, which integrates the terms freely generated by S, and which is equipped with reductions according to the rules given in A. We call this initial object the programming language generated by (S, A). Models of a 2-signature are built from relative monads and modules over such monads. Through the use of monads, the models – and in particular, the initial model – come equipped with a substitution operation that is compatible with reduction in a suitable sense.

The initiality theorem is formalized in the proof assistant Coq, yielding a machinery which, when fed with a 2-signature, provides the associated programming language with reduction relation and certified substitution.
Relating timed and register automata
Authors: FIGUEIRA DIEGO , HOFMAN PIOTR , LASOTA SŁAWOMIR
Published: December 2014

Timed and register automata are well-known models of computation over timed and data words, respectively. The former has clocks that allow to test the lapse of time between two events, whilst the latter includes registers that can store data values for later comparison. Although these two models behave differently in appearance, several decision problems have the same (un)decidability and complexity results for both models. As a prominent example, emptiness is decidable for alternating automata with one clock or register, both with non-primitive recursive complexity. This is not by chance.

This work confirms that there is indeed a tight relationship between the two models. We show that a run of a timed automaton can be simulated by a register automaton over ordered data domain, and conversely that a run of a register automaton can be simulated by a timed automaton. These are exponential time reductions hold both in the finite and infinite words settings. Our results allow to transfer decidability results back and forth between these two kinds of models, as well complexity results modulo an exponential time reduction. We justify the usefulness of these reductions by obtaining new results on register automata.
Role of non-genomic androgen signalling in suppressing proliferation of fibroblasts and fibrosarcoma cells
Authors: Castoria G , Giovannelli P , Di Donato M , Ciociola A , Hayashi R , Bernal F , Appella E , Auricchio F , Migliaccio A
Published: December 2014

The functions of androgen receptor (AR) in stromal cells are still debated in spite of the demonstrated importance of these cells in organ development and diseases. Here, we show that physiological androgen concentration (10 nM R1881 or DHT) fails to induce DNA synthesis, while it consistently stimulates cell migration in mesenchymal and transformed mesenchymal cells. Ten nanomolar R1881 triggers p27 Ser10 phosphorylation and its stabilization in NIH3T3 fibroblasts. Activation of Rac and its downstream effector DYRK 1B is responsible for p27 Ser10 phosphorylation and cell quiescence. Ten nanomolar androgen also inhibits transformation induced by oncogenic Ras in NIH3T3 fibroblasts. Overexpression of an AR mutant unable to interact with filamin A, use of a small peptide displacing AR/filamin A interaction, and filamin A knockdown indicate that the androgen-triggered AR/filamin A complex regulates the pathway leading to p27 Ser10 phosphorylation and cell cycle arrest. As the AR/filamin A complex is also responsible for migration stimulated by 10 nM androgen, our report shows that the androgen-triggered AR/filamin A complex controls, through Rac 1, the decision of cells to halt cell cycle and migration. This study reveals a new and unexpected role of androgen/AR signalling in coordinating stromal cell functions.