bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective visual design and communication practices for research posters: Exemplars based on the theory and practice of multimedia learning and rhetoric
Authors: Pedwell Rhianna K. , Hardy James A. , Rowland Susan L.
Published: December 2016

Evidence shows that science graduates often do not have the communication skills they need to meet workplace standards and expectations. One common mode of science communication is the poster. In a review of the literature we show that poster design is historically problematic, and that the guidance provided to students as they create posters for assessment is frequently inconsistent. To address this inconsistency we provide some guiding design principles for posters that are grounded in communication theory and the fundamentals of rhetoric. We also present three nondiscipline‐specific example posters with accompanying notes that explain why the posters are examples of poor, average, and excellent poster design. The subject matter for the posters is a fabricated set of experiments on a topic that could not actually be the subject of research. Instructors may use these resources with their students, secure in the knowledge that they do not and will never represent an answer set to an extant assessment item. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(3):249–261, 2017.
An HPLC‐UV method for determining plasma dimethylacetamide concentrations in patients receiving intravenous busulfan
Authors: Cendana Mildred , Lee Samiuela , Upadhyay Parth J. , Byrne Jennifer A. , Shaw Peter J. , Earl John , Nath Christa E.
Published: December 2016

Dimethylacetamide (DMA) is a solvent used in the preparation of intravenous busulfan, an alkylating agent used in blood or marrow transplantation. DMA may contribute to hepatic toxicity, so it is important to monitor its clearance. The aim of this study was to develop an HPLC‐UV assay for measurement of DMA in human plasma. After precipitation of plasma proteins with acetonitrile followed by dilution (1:4) with water, the extract was injected onto the HPLC and detected at 195 nm. Separation was performed using a Cogent‐HPS 5 μm C18 column (250 × 4.6 mm) preceded by a Brownlee 7 μm RP18, pre‐column (1.5 cm × 3.2 mm). The mobile phase was 25 mm sodium phosphate buffer (pH 3), containing 2.5% (v/v) acetonitrile and 0.0005% (v/v) sodium‐octyl‐sulfonate. Using a flow rate of 1 mL/min, the retention times of DMA and the internal standard (IS), 2‐chloroacetamide, were 9.5 and 3.5 min, respectively. Peak area ratio (DMA:IS) was a linear function of concentration from 1 to 1000 μg/mL. There was excellent intraday precision (<5% for 5–700 μg/mL DMA), accuracy (<3% deviation from the true concentration) and recovery (74–98%). The limits of detection and quantification were 1 and 5 μg/mL, respectively. In eight children who received intravenous busulfan, DMA concentrations ranged from 110 to 438 μg/mL.
Discovery and identification of potential biomarkers for alcohol‐induced oxidative stress based on cellular metabolomics
Authors: Hu Qingping , Wei Jianteng , Liu Yewei , Fei Xiulan , Hao Yuwei , Pei Dong , Di Duolong
Published: December 2016

Biomarkers involved in alcohol‐induced oxidative stress play an important role in alcoholic liver disease prevention and diagnosis. Alcohol‐induced oxidative stress in human liver L‐02 cells was used to discover the potential biomarkers. Metabolites from L‐02 cells induced by alcohol were measured by high‐performance liquid chromatography and mass spectrometry. Fourteen metabolites that allowed discrimination between control and model groups were discovered by multivariate statistical data analysis (i.e. principal components analysis, orthogonal partial least‐squares discriminate analysis). Based on the retention time, UV spectrum and LC–MS findings of the samples and compared with the authentic standards, eight biomarkers involved in alcohol‐induced oxidative stress, namely, malic acid, oxidized glutathione, γ‐glutamyl‐cysteinyl‐glycine, adenosine triphosphate, phenylalanine, adenosine monophosphate, nitrotyrosine and tryptophan, were identified. These biomarkers offered important targets for disease diagnosis and other researches.
Analytical method for urinary metabolites as biomarkers for monitoring exposure to phthalates by gas chromatography/mass spectrometry
Authors: Yoshida Toshiaki
Published: December 2016

Phthalates, widely used as plasticizers, have been detected in indoor air, but there have been few reports on methods of analyzing urinary metabolites as biomarkers to monitor exposure to di‐n‐pentyl phthalate or di‐n‐hexyl phthalate. Presented here is a cost‐effective and sensitive analytical method for the determination of urinary metabolites of phthalates containing these two compounds. Nine urinary phthalate metabolites were enzymatically hydrolyzed and extracted with toluene: monomethyl phthalate, monoethyl phthalate, monoisobutyl phthalate, mono‐n‐butyl phthalate, mono‐n‐pentyl phthalate, mono‐n‐hexyl phthalate, monocyclohexyl phthalate, monobenzyl phthalate and mono(2‐ethyl‐5‐carboxypentyl) phthalate. After transformation to their tert‐butyldimethylsilyl derivatives, they were analyzed by gas chromatography/mass spectrometry in the electron impact ionization mode. The calibration curves for the metabolites were linear at urinary concentrations of up to 30 μg/L, showing that they could be determined accurately and precisely (detection limits 0.1–0.4 μg/L, quantification limits 0.3–1.3 μg/L). The urine samples collected could be stored for up to 1 month at −20°C. The proposed analytical method was used to examine urine samples from seven healthy volunteers. This method should be useful for monitoring phthalate exposure in the general population.
Skeletal muscle atrophy is induced by Fbxw7β via atrogene upregulation
Authors: Shin Kyungshin , Ko Young‐Gyu , Jeong Jaemin , Kwon Heechung
Published: December 2016

Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin‐1 and MuRF‐1) and reduced myoblast differentiation. In addition, endogenous expression of Fbxw7β was also upregulated by dexamethasone, which mimics muscle atrophy in vitro, accompanied by induction of myogenin and atrogene expression in primary myoblasts. Functional analysis of Fbxw7β using short hairpin RNA (shRNA) and a dominant‐negative mutant (ΔFbox) suggested that Fbxw7β regulated muscle atrophy in vitro and in vivo. In particular, ΔFbox did not reduce the sizes of muscle fibers and did not induce myogenin and atrogene expression in vivo. Therefore, our findings demonstrated, for the first time, that Fbxw7β induced muscle atrophic phenotypes via atrogenes in adult muscle precursor cells and myofibers; this mechanism could be a potential therapeutic target for skeletal muscle atrophy.
The Chemistry of a Non‐Interacting Vicinal Frustrated Phosphane/Borane Lewis Pair
Authors: Elmer Lisa‐Maria , Kehr Gerald , Daniliuc Constantin G. , Siedow Melanie , Eckert Hellmut , Tesch Matthias , Studer Armido , Williams Kamille , Warren Timothy H. , Erker Gerhard
Published: December 2016

The dimesitylphosphinocyclopentene/HB(C6F5)2‐derived vicinal trans‐1,2‐P/B frustrated Lewis pair (FLP) 4 shows no direct phosphane–borane interaction. Toward some reagents it behaves similar to an intermolecular FLP; it cleaves dihydrogen, deprotonates terminal alkynes, and adds to organic carbonyl compounds including CO2. It shows typical intramolecular FLP reaction modes (cooperative 1,1‐additions) to mesityl azide, to carbon monoxide, and to NO. The latter reaction yields a persistent P/B FLPNO nitroxide radical, which undergoes H‐atom abstraction reactions. The FLP 4 serves as a template for the CO reduction by [HB(C6F5)2] to generate a FLP‐η2‐formylborane. The formylborane moiety is removed from the FLP template by reaction with pyridine to yield a genuine pyridine stabilized formylborane that undergoes characteristic borane carbaldehyde reactions (Wittig olefination, imine formation). Most new products were characterized by X‐ray diffraction.
Graphene‐Oxide‐Based Enzyme Nanoarchitectonics for Substrate Channeling
Authors: Mathesh Motilal , Liu Jingquan , Barrow Colin J. , Yang Wenrong
Published: December 2016

The controlled spatial organization or compartmentalization of multi‐enzyme cascade reactions to transfer a substrate from one enzyme to another for substrate channeling on scaffolds has sparked increasing interest in recent years. Here, we use graphene oxides to study the dependence of the activity of cascade reactions in a closely packed, randomly immobilized enzyme system on a 2 D scaffold. We first observe that the hydrophobicity of graphene oxides and various enzyme architectures for co‐immobilized systems are important attributes for achieving high product‐conversion rates. A transient time close to 0 s can be achieved if enzymes are randomly immobilized close to one another, owing to direct molecular channeling. This contributes to overcoming complications regarding control of the spatial arrangement of the enzymes. Furthermore, a fabricated bienzyme paper can be used for glucose detection with high stability, reusability, and enhanced substrate channeling. Our findings provide new guidance for enzyme orientation on 2 D scaffolds, which may be extrapolated to other multienzyme cascade systems.
Three‐Dimensional Fibrous Network of Na0.21MnO2 for Aqueous Sodium‐Ion Hybrid Supercapacitors
Authors: Karikalan Natarajan , Karuppiah Chelladurai , Chen Shen‐Ming , Velmurugan Murugan , Gnanaprakasam Periyasami
Published: December 2016

Sodium‐ion hybrid supercapacitors are potential energy‐storage devices and have recently received enormous interest. However, the development of cathode materials and the use of nonaqueous electrolyte remain a great challenge. Hence, aqueous Na‐ion hybrid supercapacitors based on a three‐dimensional network of NaMnO2 were developed. The cathode material was synthesized by the electro‐oxidation of potassium manganese hexacyanoferrate nanocubes. The oxidized compound was confirmed to be Na0.21MnO2 by various physical characterization methods. Manganese dioxide is a well‐characterized material for aqueous asymmetric pseudocapacitors, but its usage at high operating voltages is limited due to the electrochemical stability of water. Nevertheless, high‐potential and high‐performance aqueous supercapacitors exhibiting a cell potential of 2.7 V were developed. Further, the practical applicability of an asymmetric supercapacitor based on NaMnO2 (cathode) and reduced graphene oxide (anode) was demonstrated by powering a 2.1 V red LED.
A Simple Approach To Develop Tailored Mesoporosity in Nanostructured Heteropolysalts
Authors: Alcañiz‐Monge Juan , Trautwein Guido , El Bakkali Bouchra , Reinoso Santiago
Published: December 2016

In this study, we describe a very simple approach to the development of tailored mesoporosity in any nanostructured heteropolysalt with control over both the mesoporous volume and the pore size. This approach, which consists in the treatment of a solid microporous precursor with a basic agent, has been tested on the ammonium salt of the Keggin‐type [PMo12O40]3− heteropolyanion and constitutes a novel procedure for the preparation of mesoporous solids with no precedents. The results obtained in this study allow two main conclusions to be drawn: 1) the micro‐ and mesoporous structures in the heteropolysalt nanoparticles are independent from each other and 2) the development of mesoporosity in the solid material must be related to a process of alkaline degradation within the core of the nanocrystals that aggregate into the particles. These results afford valuable additional information to the present model of porosity that has been established for heteropolysalts.
The Delicate Balance of Preorganisation and Adaptability in Multiply Bonded Host–Guest Complexes
Authors: von Krbek Larissa K. S. , Achazi Andreas J. , Schoder Stefan , Gaedke Marius , Biberger Tobias , Paulus Beate , Schalley Christoph A.
Published: December 2016

Rigidity and preorganisation are believed to be required for high affinity in multiply bonded supramolecular complexes as they help reduce the entropic penalty of the binding event. This comes at the price that such rigid complexes are sensitive to small geometric mismatches. In marked contrast, nature uses more flexible building blocks. Thus, one might consider putting the rigidity/high‐affinity notion to the test. Multivalent crown/ammonium complexes are ideal for this purpose as the monovalent interaction is well understood. A series of divalent complexes with different spacer lengths and rigidities has thus been analysed to correlate chelate cooperativities and spacer properties. Too long spacers reduce chelate cooperativity compared to exactly matching ones. However, in contrast to expectation, flexible guests bind with chelate cooperativities clearly exceeding those of rigid structures. Flexible spacers adapt to small geometric host–guest mismatches. Spacer–spacer interactions help overcome the entropic penalty of conformational fixation during binding and a delicate balance of preorganisation and adaptability is at play in multivalent complexes.
Total Synthesis of Mycobacterium tuberculosis Dideoxymycobactin‐838 and Stereoisomers: Diverse CD1a‐Restricted T Cells Display a Common Hierarchy of Lipopeptide Recognition
Authors: Cheng Janice M. H. , Liu Ligong , Pellicci Daniel G. , Reddiex Scott J. J. , Cotton Rachel N. , Cheng Tan‐Yun , Young David C. , Van Rhijn Ildiko , Moody D. Branch , Rossjohn Jamie , Fairlie David P. , Godfrey Dale I. , Williams Spencer J.
Published: December 2016

Mycobacterium tuberculosis produces dideoxymycobactin‐838 (DDM‐838), a lipopeptide that potently activates T cells upon binding to the MHC‐like antigen‐presenting molecule CD1a. M. tuberculosis produces DDM‐838 in only trace amounts and a previous solid‐phase synthesis provided sub‐milligram quantities. We describe a high‐yielding solution‐phase synthesis of DDM‐838 that features a Mitsunobu substitution that avoids yield‐limiting epimerization at lysine during esterification, and amidation conditions that prevent double‐bond isomerization of the Z‐C20:1 acyl chain, and provides material with equivalent antigenicity to natural DDM‐838. Isomers of DDM‐838 that varied in stereochemistry at the central lysine and the C20:1 acyl chain were compared for their ability to be recognised by CD1a‐restricted T cell receptors (TCRs). These TCRs, derived from unrelated human donors, exhibited a similar spectrum of reactivity towards the panel of DDM‐838 isomers, highlighting the exquisite sensitivity of lipopeptide‐reactive T cells for the natural DDM stereochemistry.
Chiral Primary Amine Catalyzed Asymmetric α‐Benzylation with In Situ Generated ortho‐Quinone Methides
Authors: Zhu Yunbo , Zhang Wen‐Zhao , Zhang Long , Luo Sanzhong
Published: December 2016

A dual activation strategy integrating primary amine catalysis and Lewis base activation has been developed for an asymmetric α‐benzylation reaction. Enamines derived from β‐ketocarbonyls could react effectively with in situ generated ortho‐quinone methides under Lewis base activation in asymmetric α‐benzylation of β‐ketocarbonyls and α‐branched aldehydes. The approach enables the creation of acyclic all‐carbon quaternary stereocenters with excellent enantioselectivities and good activity.
Frustrated Lewis Pair‐Like Reactivity of Rare‐Earth Metal Complexes: 1,4‐Addition Reactions and Polymerizations of Conjugated Polar Alkenes
Authors: Xu Pengfei , Yao Yingming , Xu Xin
Published: December 2016

Three rare‐earth aryloxide ion pairs {[L1REOAr]+/[B(C6F5)4]−; L1=CH3C(2,6‐iPr2C6H3N)CHC(CH3)(NCH2CH2PPh2); RE=Sc, Y, Lu; Ar=2,6‐tBu2C6H3} were reported that feature rare‐earth/phosphorus (RE/P) combinations exhibiting frustrated Lewis pair (FLP)‐like 1,4‐addition reactions towards conjugated carbonyl substrates (e.g., enone, ynone, and acrylic substrates). Furthermore, these RE/P complexes were found to be effective catalysts for the polymerization of conjugated polar alkene monomers. Mechanistic studies revealed that the rare‐earth metal‐catalyzed polymerizations were initiated by new FLP‐type 1,4‐additions rather than traditional and ubiquitous covalent RE−E (E=H, C, N, etc.) bond insertion or single‐electron transfer.
DaNa 2.0 – verlässliche Informationen zur Sicherheit von marktüblichen Nanomaterialien
Authors: Steinbach Christoph , Bohmer Nils , Krug Harald F. , Kühnel Dana , Nau Katja , Paul Florian , Reithel Sarah , Marquardt Clarissa
Published: December 2016

Sowohl Wissenschaftler als auch der Bürger brauchen verlässliche Informationen, wenn sie faktenorientiert über die Sicherheit von Nanomaterialien diskutieren wollen. Nicht alle Artikel zu diesem Thema eignen sich für eine Risikoabschätzung. Deshalb ist es notwendig, geeignete von ungeeigneten Artikeln zu trennen. Dies ist das Ziel des vom Bundesministerium für Bildung und Forschung geförderten Projekts DaNa 2.0. Hier werden wissenschaftliche Veröffentlichungen in einem transparenten Verfahren unter Verwendung eines Literatur‐Kriterienkatalog evaluiert und die Ergebnisse in Form von allgemeinverständlichen Artikeln auf der Projekt‐Website publiziert.
A soft sensor for the sulphur dioxide converter in an industrial smelter
Authors: He Jianjun , Zhang Junfeng , Shang Helen
Published: December 2016

In metal productions from sulphide ores, sulphur dioxide (SO2) is generated when the ore concentrate is smelted. To minimize emission of SO2 to the atmosphere, sulphuric acid plants are used to convert SO2 gas into sulphuric acid product in smelters. A SO2 to sulphur dioxide (SO3) converter, where SO2 is oxidized to SO3 with the help of catalyst, is the key unit in a sulphuric acid plant. For monitoring the converter, temperature of the reactor is extensively measured at various locations, but the concentration of SO2 is barely measured or only measured at very limited points due to the difficulty and costs involved. In this paper, a soft sensor is developed to estimate the conversion ratio and concentration of SO2. The soft sensor is derived based on the steady state mass balance model of the converter and dynamic data analysis. From the proposed soft sensor, conversion ratio and concentration of SO2 can be estimated from available industrial real‐time measurement.
Synuclein‐γ in uterine serous carcinoma impacts survival: An NRG Oncology/Gynecologic Oncology Group study
Authors: Winder Abigail D. , Maniar Kruti P. , Wei Jian‐Jun , Liu Dachao , Scholtens Denise M. , Lurain John R. , Schink Julian C. , Buttin Barbara M. , Filiaci Virginia L. , Lankes Heather A. , Ramirez Nilsa C. , Park Kay , Singh Meenakshi , Lieberman Richard W. , Mannel Robert S. , Powell Matthew A. , Backes Floor J. , Mathews Cara A. , Pearl Michael L. , Secord Angeles Alvarez , Peace David J. , Mutch David G. , Creasman William T. , Kim J. Julie
Published: December 2016

BACKGROUND

Synuclein‐γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG‐8023).

METHODS

High‐density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression‐free survival were assessed using log‐rank tests and Cox proportional‐hazards models, which also were adjusted for age, race, and stage.

RESULTS

The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log‐rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91‐1.9 in adjusted Cox model). The progression‐free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log‐rank P = .0081; HR, 1.36; 95% CI, 0.96‐1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54‐11.45]; p16: HR, 1.95 [95% CI, 1.01‐3.75]) and progression‐free survival (p53: HR, 2.16 [95% CI, 1.09‐4.27]; p16: HR, 1.53 [95% CI, 0.87‐2.69]) compared with low levels.

CONCLUSIONS

This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144–1155. © 2016 American Cancer Society.
Interobserver reproducibility of cytologic p16INK4a/Ki‐67 dual immunostaining in human papillomavirus‐positive women
Authors: Benevolo Maria , Allia Elena , Gustinucci Daniela , Rollo Francesca , Bulletti Simonetta , Cesarini Elena , Passamonti Basilio , Giovagnoli Maria Rosaria , Carico Elisabetta , Carozzi Francesca M. , Mongia Alessandra , Fantacci Giulia , Confortini Massimo , Rubino Teresa , Fodero Cristina , Prandi Sonia , Marchi Natalina , Farruggio Angelo , Coccia Anna , Macrì Luigia , Ghiringhello Bruno , Ronco Guglielmo , Bragantini Emma , Polla Enzo , Maccallini Vincenzo , Negri Giovanni , Giorgi Rossi Paolo ,   for the New Technologies for Cervical Cancer Screening 2 (NTCC2) Working Group
Published: December 2016

BACKGROUND

The accumulation of cyclin‐dependent kinase inhibitor 2A (p16ink4a) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16ink4a and Ki‐67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed.

METHODS

Forty‐two immunostained, liquid‐based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists.

RESULTS

The overall κ value was 0.612 (95% confidence interval [CI], 0.523‐0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643‐0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388‐0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358‐0.642] and κ = 0.521 [95% CI, 0.240‐0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384‐0.866]; second evaluation, κ = 0.403 [95% CI, 0.182‐0.643]).

CONCLUSIONS

Dual staining for p16 ink4a and Ki‐67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212–220. © 2016 American Cancer Society.
Low latency flexible FPGA implementation of point multiplication on elliptic curves over GF(p)
Authors: Javeed Khalid , Wang Xiaojun
Published: December 2016

Elliptic curve cryptography (ECC) is a branch of Public‐Key cryptography that is widely accepted for secure data exchange in many resource‐limited devices. This paper presents a novel hardware cryptographic processor for ECC over general prime field GF(p). It is optimized on circuit level by introducing new parallel modular multiplication algorithm with its efficient hardware architecture, which offers significant improvement over the previously used techniques. Subsequently, on the system level, it is optimized by exploiting available high degree of parallelism using projective coordinates by incorporating four parallel multiplier units. The proposed hardware is implemented on Xilinx Virtex‐4 and Virtex‐6 field programmable gate arrays. A 256‐bit scalar multiplication is completed in 1.43 ms and 2.96 ms in a cycle count of 207 1K on Virtex‐6 and Virtex‐4 field programmable gate array paltforms, respectively. The Virtex‐6 implementation attains a maximum frequency of 144 MHz, occupies 32 4K look‐up‐tables, whereas on Virtex‐4 it is about 70 MHz with 35 7K slices. The results show that the proposed design offers a significant improvement in computation time with a significant reduction in cycle count as compared with the other reported designs. Therefore, it is a good choice to be used in many ECC‐based schemes. Copyright © 2016 John Wiley & Sons, Ltd.
A novel clinical score (InterTAK Diagnostic Score) to differentiate takotsubo syndrome from acute coronary syndrome: results from the International Takotsubo Registry
Authors: Ghadri Jelena R. , Cammann Victoria L. , Jurisic Stjepan , Seifert Burkhardt , Napp L. Christian , Diekmann Johanna , Bataiosu Dana Roxana , D'Ascenzo Fabrizio , Ding Katharina J. , Sarcon Annahita , Kazemian Elycia , Birri Tanja , Ruschitzka Frank , Lüscher Thomas F. , Templin Christian ,   InterTAK co‐investigators
Published: December 2016

Aims

Clinical presentation of takotsubo syndrome (TTS) mimics acute coronary syndrome (ACS) and does not allow differentiation. We aimed to develop a clinical score to estimate the probability of TTS and to distinguish TTS from ACS in the acute stage.

Methods and results

Patients with TTS were recruited from the International Takotsubo Registry (
www.takotsubo‐registry.com) and ACS patients from the leading hospital in Zurich. A multiple logistic regression for the presence of TTS was performed in a derivation cohort (TTS, n = 218; ACS, n = 436). The best model was selected and formed a score (InterTAK Diagnostic Score) with seven variables, and each was assigned a score value: female sex 25, emotional trigger 24, physical trigger 13, absence of ST‐segment depression (except in lead aVR) 12, psychiatric disorders 11, neurologic disorders 9, and QTc prolongation 6 points. The area under the curve (AUC) for the resulting score was 0.971 [95% confidence interval (CI) 0.96–0.98] and using a cut‐off value of 40 score points, sensitivity was 89% and specificity 91%. When patients with a score of ≥50 were diagnosed as TTS, nearly 95% of TTS patients were correctly diagnosed. When patients with a score ≤31 were diagnosed as ACS, ∼95% of ACS patients were diagnosed correctly. The score was subsequently validated in an independent validation cohort (TTS, n = 173; ACS, n = 226), resulting in a score AUC of 0.901 (95% CI 0.87–0.93).

Conclusion

The InterTAK Diagnostic Score estimates the probability of the presence of TTS and is able to distinguish TTS from ACS with a high sensitivity and specificity.

Trial registration: NCT0194762
Improved consistency in 2D gel electrophoresis: Sheep plasma as a test case
Authors: Brown Stuart , Norris Gillian
Published: December 2016

Two‐dimensional (2D) gel electrophoresis is a well‐proven proteomic technique; however, sample‐specific optimisation can often be necessary in order to get consistent quantitation. In particular, plasma samples are often smeared on 2D gels making spot matching difficult. A variety of different sample preparation and 2D methods were tested by using sheep plasma, and it was found that lowering sample pH prior to precipitation, using a long voltage gradient for isoelectric focusing and the inclusion of carrier ampholytes in the electrode wicks, improved both the quality and consistency of spot resolution. Analysis of the internal standards from two different DIGE experiments, one with conventional methodology and one with the improved method, showed that along with substantially improving the number of spots resolved, the average CV (coefficient of variation) of matched standards was lower with the new method. 428 matched spots were found using the improved method compared to 208 matched spots using conventional methodology. For the 174 spots that were matched between the two DIGE experiments, the average CV's of spot volumes were also significantly lower, at 0.20 for the new method compared to 0.24 for the conventional method (p < 0.001).
EpiNet as a way of involving more physicians and patients in epilepsy research: Validation study and accreditation process
Authors: Bergin Peter S. , Beghi Ettore , Sadleir Lynette G. , Brockington Alice , Tripathi Manjari , Richardson Mark P. , Bianchi Elisa , Srivastava Kavita , Jayabal Jayaganth , Legros Benjamin , Ossemann Michel , McGrath Nicole , Verrotti Alberto , Tan Hui Jan , Beretta Simone , Frith Richard , Iniesta Ivan , Whitham Emma , Wanigasinghe Jithangi , Ezeala‐Adikaibe Birinus , Striano Pasquale , Rosemergy Ian , Walker Elizabeth B. , Alkhidze Maia , Rodriguez‐Leyva Ildefonso , Ramírez González Jose Alfredo , D'Souza Wendyl J. ,   the EpiNet Study Group
Published: December 2016

Objective

EpiNet was established to encourage epilepsy research. EpiNet is used for multicenter cohort studies and investigator‐led trials. Physicians must be accredited to recruit patients into trials. Here, we describe the accreditation process for the EpiNet‐First trials.

Methods

Physicians with an interest in epilepsy were invited to assess 30 case scenarios to determine the following: whether patients have epilepsy; the nature of the seizures (generalized, focal); and the etiology. Information was presented in two steps for 23 cases. The EpiNet steering committee determined that 21 cases had epilepsy. The steering committee determined by consensus which responses were acceptable for each case. We chose a subset of 18 cases to accredit investigators for the EpiNet‐First trials. We initially focused on 12 cases; to be accredited, investigators could not diagnose epilepsy in any case that the steering committee determined did not have epilepsy. If investigators were not accredited after assessing 12 cases, 6 further cases were considered. When assessing the 18 cases, investigators could be accredited if they diagnosed one of six nonepilepsy patients as having possible epilepsy but could make no other false‐positive errors and could make only one error regarding seizure classification.

Results

Between December 2013 and December 2014, 189 physicians assessed the 30 cases. Agreement with the steering committee regarding the diagnosis at step 1 ranged from 47% to 100%, and improved when information regarding tests was provided at step 2. One hundred five of the 189 physicians (55%) were accredited for the EpiNet‐First trials. The kappa value for diagnosis of epilepsy across all 30 cases for accredited physicians was 0.70.

Significance

We have established criteria for accrediting physicians using EpiNet. New investigators can be accredited by assessing 18 case scenarios. We encourage physicians with an interest in epilepsy to become EpiNet‐accredited and to participate in these investigator‐led clinical trials.
Survey on covert channels in virtual machines and cloud computing
Authors: Betz Johann , Westhoff Dirk , Müller Günter
Published: December 2016

Covert channels have been known for a long time because of their versatile forms of appearance. For nearly every technical improvement or change in technology, such channels have been (re‐)created or known methods have been adapted. For example, the introduction of hyperthreading technology has introduced new possibilities for covert communication between malicious processes because they can now share the arithmetic logical unit as well as the L1 and L2 caches, which enable establishing multiple covert channels. Even virtualization, which is known for its isolation of multiple machines, is prone to covert‐ and side‐channel attacks because of the sharing of resources. Therefore, it is not surprising that cloud computing is not immune to this kind of attacks. Moreover, cloud computing with multiple, possibly competing users or customers using the same shared resources may elevate the risk of illegitimate communication. In such a setting, the “air gap” between physical servers and networks disappears, and only the means of isolation and virtual separation serve as a barrier between adversary and victim. In the work at hand, we will provide a survey on vulnerable spots that an adversary could exploit trying to exfiltrate private data from target virtual machines through covert channels in a cloud environment. We will evaluate the feasibility of example attacks and point out proposed mitigation solutions in case they exist.
Cognitive impairment in Parkinson's disease: impact on quality of life of carers
Authors: Lawson RA , Yarnall AJ , Johnston F , Duncan GW , Khoo TK , Collerton D , Taylor JP , Burn DJ ,   On behalf of the ICICLE‐PD study group
Published: December 2016

Background

The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers.

Methods

Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains.

Results

Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01).

Conclusions

Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self‐efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.
Bisphosphonate Withdrawal: Effects on Bone Formation and Bone Resorption in Maturing Male Mice
Authors: Ko Frank C , Karim Lamya , Brooks Daniel J , Bouxsein Mary L , Demay Marie B
Published: December 2016

Bisphosphonates are being increasingly used to treat pediatric patients with skeletal disorders. However, the effects of long-term bisphosphonate therapy and cessation of therapy during growth are unclear. Thus, studies were undertaken to determine the effects of alendronate discontinuation after treatment of C57Bl/6 mice during the period of rapid skeletal growth. Compared with vehicle-treated mice, 16 weeks of alendronate treatment starting at age 18 days resulted in a 3.7-fold increase in trabecular bone in the setting of suppressed bone formation. Alendronate therapy for 8 weeks followed by 8 weeks of vehicle treatment resulted in a more pronounced increase in trabecular bone compared with mice treated with alendronate for 16 weeks (1.7-fold) and to vehicle-treated controls (6.5-fold). Mice that received alendronate for 8 weeks followed by 8 weeks of vehicle exhibited increased osteoblast surface (2.5-fold), mineralizing surface (5.7-fold), and bone formation rate (5.1-fold) compared with mice treated continuously with alendronate. However, these parameters were not restored to the levels observed in the vehicle-treated mice. Thus, partial resumption of bone formation upon cessation of bisphosphonate therapy leads to a greater increase in trabecular bone than that found when bisphosphonates are administered continuously to growing mice. These data suggest that intermittent administration of bisphosphonates may optimize their beneficial effects on the growing skeleton. © 2017 American Society for Bone and Mineral Research.
On the Hamilton–Waterloo Problem with Odd Orders
Authors: Burgess A. C. , Danziger P. , Traetta T.
Published: December 2016

Given nonnegative integers , the Hamilton–Waterloo problem asks for a factorization of the complete graph into α ‐factors and β ‐factors. Without loss of generality, we may assume that . Clearly, v odd, , , and are necessary conditions. To date results have only been found for specific values of m and n. In this paper, we show that for any integers , these necessary conditions are sufficient when v is a multiple of and , except possibly when or 3. For the case where we show sufficiency when with some possible exceptions. We also show that when are odd integers, the lexicographic product of with the empty graph of order n has a factorization into α ‐factors and β ‐factors for every , , with some possible exceptions.
Vascular endothelial growth factor G+405C polymorphism may contribute to the risk of developing papillary thyroid carcinoma
Authors: Bingül İlknur , Vural Pervin , Doğru‐Abbasoğlu Semra , Çil Esra , Uysal Müjdat
Published: December 2016

Background

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Vascular endothelial growth factor (VEGF) is a mediator implicated with cell proliferation, differentiation and migration, and monocyte/macrophage chemotaxis. In present study, we aimed to investigate the relationship between VEGF gene polymorphisms (G+405C, T‐460C, and A‐2578C) and PTC susceptibility.

Methods

DNA was isolated from peripheral blood leukocytes of 127 patients with PTC and 203 healthy controls. Genotyping was performed by real‐time PCR. Association of genotypes with susceptibility of PTC was analyzed with multivariate logistic regression adjusted for age, gender and smoking status.

Results and Conclusion

In G+405C polymorphism, the frequencies of C allele (related with increased VEGF production) and combined CG+CC genotype were found to be higher (3.5 and 5‐fold, respectively) among patients with PTC than controls (P<.001). However, VEGF T‐460C and A‐2578C polymorphisms are not associated with PTC risk. There was no relationship between VEGF polymorphisms and clinical/laboratory parameters of PTC. Haplotype analysis demonstrated that there was a strong linkage disequilibrium (LD) between −460/−2578 (D’=.89, r2=.79), weak LD between +405/−460 (D’=.422, r2=.035), and +405/−2578 (D’=.43, r2=.038) locuses. Additionally, the +405/−460/−2578 GTA haplotype was found to be protective, whereas CTA haplotype to be related with increased PTC risk. As a conclusion, we suggest that VEGF G+405C polymorphism is associated with increased risk of PTC.
Rabs, Membrane Dynamics, and Parkinson's Disease
Authors: Tang Bor Luen
Published: December 2016

Genes encoding cellular membrane trafficking components, namely RAB7L1 and RAB39B, are more recently recognized factors associated with Parkinson's disease (PD). Encoded by a gene within the PARK16 locus, RAB7L1 interacts with Leucine‐rich repeat kinase 2 (LRRK2) to act in intracellular transport processes that are likely important for neuronal survival and function. LRRK2 also directly phosphorylates a number of other Rab proteins. On the other hand, nonsense and missense mutations of the X‐chromosome localized RAB39B were shown to underlie X‐linked intellectual disability (ID) in male patients with early‐onset PD. The cellular or neuronal functions of RAB39B are not yet known with certainty, but it has recently been shown to play a role in glutamate receptor trafficking. Importantly, RAB39B is also functionally connected to components for autophagy regulation, which affects α‐synuclein processing and clearance. In this review, we discuss the association of Rabs with PD pathology, and potential etiological mechanisms whereby defects or deficiencies in certain Rab proteins could lead to PD susceptibility. J. Cell. Physiol. 232: 1626–1633, 2017. © 2016 Wiley Periodicals, Inc.
Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPARα‐Dependent AMPK Activation
Authors: de Souza Camila O. , Teixeira Alexandre A.S. , Biondo Luana A. , Lima Junior Edson A. , Batatinha Helena A.P. , Rosa Neto Jose C.
Published: December 2016

Background: Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5′AMP‐activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator‐activated receptor‐α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. Objective: To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. Methods: C57BL6 and PPARα knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high‐fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. Results: Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP‐1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF‐21 and stimulated the expression of PPARα. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF‐21 in liver of PPARα KO mice. Conclusions: In mice fed with a high‐fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF‐21, dependent on PPARα. J. Cell. Physiol. 232: 2168–2177, 2017. © 2016 Wiley Periodicals, Inc.
Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway
Authors: Barreca Maria M. , Spinello Walter , Cavalieri Vincenzo , Turturici Giuseppina , Sconzo Gabriella , Kaur Punit , Tinnirello Rosaria , Asea Alexzander A. A. , Geraci Fabiana
Published: December 2016

Mouse mesoangioblasts are vessel‐associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. Therefore, they represent a promising tool in the regeneration of injured tissues. Several studies have demonstrated that homing of mesoangioblasts into blood and injured tissues are mainly controlled by cytokines/chemokines and other inflammatory factors. However, little is known about the molecular mechanisms regulating their ability to traverse the extracellular matrix (ECM). Here, we demonstrate that membrane vesicles released by mesoangioblasts contain Hsp70, and that the released Hsp70 is able to interact by an autocrine mechanism with Toll‐like receptor 4 (TLR4) and CD91 to stimulate migration. We further demonstrate that Hsp70 has a positive role in regulating matrix metalloproteinase 2 (MMP2) and MMP9 expression and that MMP2 has a more pronounced effect on cell migration, as compared to MMP9. In addition, the analysis of the intracellular pathways implicated in Hsp70 regulated signal transduction showed the involvement of both PI3K/AKT and NF‐κB. Taken together, our findings present a paradigm shift in our understanding of the molecular mechanisms that regulate mesoangioblast stem cells ability to traverse the extracellular matrix (ECM). J. Cell. Physiol. 232: 1845–1861, 2017. © 2016 Wiley Periodicals, Inc.
SV40 Infection of Mesenchymal Stromal Cells From Wharton's Jelly Drives the Production of Inflammatory and Tumoral Mediators
Authors: Cason Carolina , Campisciano Giuseppina , Zanotta Nunzia , Valencic Erica , Delbue Serena , Bella Ramona , Comar Manola
Published: December 2016

The Mesenchymal Stromal Cells from umbilical cord Wharton's jelly (WJSCs) are a source of cells with high potentiality for the treatment of human immunological disorders. Footprints of the oncogenic viruses Simian Virus 40 (SV40) and JC Virus (JCPyV) have been recently detected in human WJSCs specimens. The aim of this study is to evaluate if WJSCs can be efficiently infected by these Polyomaviruses and if they can potentially exert tumoral activity. Cell culture experiments indicated that WJSCs could sustain both SV40 and JCPyV infections. A transient and lytic replication was observed for JCPyV, while SV40 persistently infected WJSCs over a long period of time, releasing a viral progeny at low titer without evident cytopathic effect (CPE). Considering the association between SV40 and human tumors and the reported ability of the oncogenic viruses to drive the host innate immune response to cell transformation, the expression profile of a large panel of immune mediators was evaluated in supernatants by the Bioplex platform. RANTES, IL‐3, MIG, and IL‐12p40, involved in chronic inflammation, cells differentiation, and transformation, were constantly measured at high concentration comparing to control. These findings represent a new aspect of SV40 biological activity in the humans, highlighting its interaction with specific host cellular pathways. In view of these results, it seems to be increasingly urgent to consider Polyomaviruses in the management of WJSCs for their safely use as promising therapeutic source. J. Cell. Physiol. 232: 3060–3066, 2017. © 2016 Wiley Periodicals, Inc.
Cancer Cell Plasticity: Rapid Reversal of Chemosensitivity and Expression of Stemness Markers in Lung and Breast Cancer Tumorspheres
Authors: Yakisich Juan Sebastian , Azad Neelam , Kaushik Vivek , Iyer Anand Krishnan V.
Published: December 2016

In cancer cells, the reversible nature of the stemness status in terms of chemoresistance has been poorly characterized. In this study, we have simulated one cycle of environmental conditions to study such reversibility by first generating floating tumorspheres (FTs) from lung and breast cancer cells by culturing them in serum‐free media without the addition of any external mitogenic stimulation, and subsequently (after 2 weeks) re‐incubating them back in serum‐containing media to simulate routine culture conditions (RCCs). We found that cancer cells are extremely plastic: cells grown under RCCs become multidrug‐resistant when grown as FTs, but upon re‐incubation under RCCs quickly re‐attach and lose the acquired resistance. These phenotypic changes are accompanied by concomitant changes in the expression of key proteins associated with multiple pathways important for chemoresistance, survival, and stemness maintenance. Therefore, our strategy provides an excellent experimental model to study environmental factors that modulate the plasticity of cancer cells. J. Cell. Physiol. 232: 2280–2286, 2017. © 2016 Wiley Periodicals, Inc.
A brief history of the Open Discovery Initiative
Authors: Varnum Kenneth J.
Published: December 2016

Key points

The Open Discovery Initiative (ODI) was created in 2011 to improve participation among content providers in the then‐novel web‐scale discovery services.

The issues addressed by the ODI included metadata standards, content indexing, and availability of licensed content in discovery services.

After adoption of the recommended practice in June 2014, a new Standing Committee has been formed to address unfinished business and implementation.

A challenge for the ODI is finding the right balance between the needs of commercial partners and library customers.