bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of time‐to‐onset in statistical signal detection of adverse drug reactions: a comparison with disproportionality analysis in spontaneous reports from the Netherlands
Authors: Scholl Joep H. G. , van Puijenbroek Eugène P. 
Published: September 2016

AbstractPurposeIn pharmacovigilance, the commonly used disproportionality analysis (DPA) in statistical signal detection is known to have its limitations. The aim of this study was to investigate the value of the time to onset (TTO) of ADRs in addition to DPA.MethodsWe performed a pilot study using individual case safety reports (ICSRs) for three drugs (Cervarix®, nitrofurantoin and simvastatin) from the Lareb spontaneous reporting database. TTO distributions for drug – ADR associations were compared to other ADRs for the same drug and to other drugs for the same ADR using two‐sample Anderson–Darling testing. Statistically significant associations were considered true positive (TP) signals if the association was present in the official product information of the drug. Sensitivity and specificity for the TTO method were compared with the DPA method. As a measure of disproportionality, the reporting odds ratio (ROR) was used.ResultsIn general, sensitivity was lower, and specificity was higher for the TTO method compared to DPA. The TTO method showed similar sensitivity for all three drugs, whereas specificity was lower for Cervarix®. Eight additional TP signals were found using the TTO method compared to DPA.ConclusionsOur study shows that statistical signal detection based on the TTO alone resulted in a limited number of additional signals compared to DPA. We therefore conclude that the TTO method is of limited value for full database statistical screening in our setting. Copyright © 2016 John Wiley & Sons, Ltd.
PV degradation curves: non‐linearities and failure modes
Authors: Jordan Dirk C. , Silverman Timothy J. , Sekulic Bill , Kurtz Sarah R. 
Published: September 2016

AbstractPhotovoltaic (PV) reliability and durability have seen increased interest in recent years. Historically, and as a preliminarily reasonable approximation, linear degradation rates have been used to quantify long‐term module and system performance. The underlying assumption of linearity can be violated at the beginning of the life, as has been well documented, especially for thin‐film technology. Additionally, non‐linearities in the wear‐out phase can have significant economic impact and appear to be linked to different failure modes. In addition, associating specific degradation and failure modes with specific time series behavior will aid in duplicating these degradation modes in accelerated tests and, eventually, in service life prediction. In this paper, we discuss different degradation modes and how some of these may cause approximately linear degradation within the measurement uncertainty (e.g., modules that were mainly affected by encapsulant discoloration) while other degradation modes lead to distinctly non‐linear degradation (e.g., hot spots caused by cracked cells or solder bond failures and corrosion). The various behaviors are summarized with the goal of aiding in predictions of what may be seen in other systems. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Redox‐responsive core cross‐linked micelles of poly(ethylene oxide)‐b‐poly(furfuryl methacrylate) by Diels‐Alder reaction for doxorubicin release
Authors: Le Cuong M. Q. , Thi Hai Ha Pham , Cao Xuan Thang , Kim Gun‐Do , Oh Chul‐Woong , Lim Kwon Taek 
Published: September 2016

ABSTRACTRedox‐responsive core cross‐linked (CCL) micelles of poly(ethylene oxide)‐b‐poly(furfuryl methacrylate) (PEO‐b‐PFMA) block copolymers were prepared by the Diels‐Alder click‐type reaction. First, the PEO‐b‐PFMA amphiphilic block copolymer was synthesized by the reversible addition‐fragmentation chain transfer polymerization. The hydrophobic blocks of PFMA were employed to encapsulate the doxorubicin (DOX) drug, and they were cross‐linked using dithiobismaleimidoethane at 60 °C without any catalyst. Under physiological circumstance, the CCL micelles demonstrated the enhanced structural stability of the micelles, whereas dissociation of the micelles took place rapidly through the breaking of disulfide bonds in the cross‐linking linkages under reduction environment. The core‐cross‐linked micelles showed fine spherical distribution with hydrodynamic diameter of 68 ± 2.9 nm. The in vitro drug release profiles presented a slight release of DOX at pH 7.4, while a significant release of DOX was observed at pH 5.0 in the presence of 1,4‐dithiothreitol. MTT assays demonstrated that the block copolymer did not have any practically cytotoxicity against the normal HEK293 cell line while DOX‐loaded CCL micelles exhibited a high antitumor activity towards HepG2 cells. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3741–3750
Simulation study of the ability of a computationally‐designed peptide to recognize target tRNALys3 and other decoy tRNAs
Authors: Xiao Xingqing , Zhao Binwu , Agris Paul F. , Hall Carol K. 
Published: September 2016

AbstractIn this paper, we investigate the ability of our computationally‐designed peptide, Pept10 (PNWNGNRWLNNCLRG), to recognize the anticodon stem and loop (ASL) domain of the hypermodified tRNALys3 (mcm5s2U34,ms2t6A37), a reverse transcription primer of HIV replication. Five other ASLs, the singly modified ASLLys3(ms2t6A37), ASLLys3(s2U34), ASLLys3(Ψ39), ASLLys1,2(t6A37), and ASLGlu(s2U34), were used as decoys. Explicit‐solvent atomistic molecular dynamics simulations were performed to examine the process of binding of Pept10 with the target ASLLys3(mcm5s2U34,ms2t6A37) and the decoy ASLs. Simulation results demonstrated that Pept10 is capable of recognizing the target ASLLys3(mcm5s2U34,ms2t6A37) as well as one of the decoys, ASLLys3(Ψ39), but screens out the other four decoy ASLs. The interchain van der Waals (VDW) and charge–charge (ELE + EGB) energies for the two best complexes were evaluated to shed light on the molecular recognition mechanism between Pept10 and ASLs. The results indicated that Pept10 recognizes and binds to the target ASLLys3 (mcm5s2U34,ms2t6A37) through residues W3 and R7 which interact with the nucleotides mcm5s2U34, U35, and ms2t6A37 via the interchain VDW energy. Pept10 also recognizes the decoy ASLLys3(Ψ39) through residue R14 which contacts the nucleotide U36 via the interchain VDW energy. Regardless of the type of ASL, the positively charged arginines on Pept10 are attracted to the negatively charged phosphate linkages on the ASL via the interchain ELE + EGB energy, thereby enhancing the binding affinity.
Establishment of in vitro soybean aphids, Aphis glycines (Hemiptera: Aphididae): a tool to facilitate studies of aphid symbionts, plant–insect interactions and insecticide efficacy
Authors: Gunadi Andika , Bansal Raman , Finer John J , Michel Andy 
Published: September 2016

AbstractBACKGROUNDStudies on plant–insect interactions of the soybean aphid, Aphis glycines (Matsumura), can be influenced by environmental fluctuations, status of the host plant and variability in microbial populations. Maintenance of aphids on in vitro‐grown plants minimizes environmental fluctuations, provides uniform host materials and permits the selective elimination of aphid‐associated microbes for more standardized controls in aphid research.RESULTSAphids were reared on sterile, in vitro‐grown soybean seedlings germinated on plant tissue culture media amended with a mixture of antimicrobials. For initiation and maintenance of in vitro aphid colonies, single aphids were inoculated onto single in vitro seedlings. After three rounds of transfer of ‘clean’ aphids to fresh in vitro seedlings, contamination was no longer observed, and aphids performed equally well when compared with those reared on detached leaves. The addition of the insecticides thiamethoxam and chlorantraniliprole to the culture medium confirmed uptake and caused significant mortality to the in vitro aphids. The use of the antimicrobial mixture removed the associated bacteria Arsenophonus but retained Buchnera and Wolbachia within the in vitro aphids.CONCLUSIONThe in vitro aphid system is a novel and highly useful tool to understand insecticidal efficacy and expand our knowledge of tritrophic interactions among plants, insects and symbionts. © 2016 Society of Chemical Industry
Vibrational band structure of nanoscale phononic crystals
Authors: Meyer R. 
Published: September 2016

AbstractThe vibrational properties of two‐dimensional phononic crystals are studied with large‐scale molecular dynamics simulations and finite element method calculation. The vibrational band structure derived from the molecular dynamics simulations shows the existence of partial acoustic band gaps along the –M direction. The band structure is in excellent agreement with the results from the finite element model, proving that molecular dynamics simulations can be used to study the vibrational properties of such complex systems. An analysis of the structure of the vibrational modes reveals how the acoustic modes deviate from the homogeneous bulk behavior for shorter wavelengths and hints toward a decoupling of vibrations in the phononic crystal.
In Situ Electrochemical Impedance Spectroscopy to Monitor Oxidative Polymerization of Aniline by HAuCl4 in Nanochannels of Track‐Etched Membrane
Authors: Sharma Manoj K. , Agarwal Rahul 
Published: September 2016

AbstractOxidative polymerisation of aniline by HAuCl4 to form gold‐polyaniline (Au‐PANI) nanocomposite in nanochannels of track‐etched membrane is monitored in situ by electrochemical impedance spectroscopy.
Facile Preparation of Fe3O4 from Fe2O3 via Reduction of Mixed Vapors Containing Lactic Acid and Water: Catalytic Deoxygenation of Lactic Acid into Propionic Acid
Authors: Zhang Yu , Li Xinli , Sun Liangwei , Tang Congming 
Published: September 2016

AbstractAn efficient and simple method for reduction of Fe2O3 into Fe3O4 using the mixed vapors including lactic acid‐water has been developed. Various characterizations such as XRD, FT‐IR, XPS, TG, BET and SEM were used to investigate in the process of Fe2O3 converted into Fe3O4. An interesting result was found: Fe2O3 is easily reduced into Fe3O4, and it stays in the state of Fe3O4 even if the time for its reduction further lengthened. The as‐prepared Fe3O4 was used to catalyze deoxygenation of lactic acid into propionic acid. Reaction temperature, residence time and stability were also discussed. It was found that enhancing reaction temperature favors deoxygenation of lactic acid into propionic acid, and shortening residence time also favors the formation of propionic acid. Especially, it offered an excellent adaptability for fluctuation of lactic acid feed flow rate.
Fused Dihydrodibenzobarrelene (Dibenzobicylco[2.2.2]octadiene) and Lactone Rings via Tandem Diels‐Alder and Condensation Reactions of Dialkyl Fumarates and 9‐Anthracenemethanol
Authors: Rowlett Jarrett R. , Plenk Christian , Deglmann Peter , Sprafke Johannes , Mülhaupt Rolf , Bruchmann Bernd 
Published: September 2016

AbstractA series of fused dihydrodibenzobarrelene (dibenzobicyclo[2.2.2]octadiene) and lactone rings were prepared from dialkyl fumarates and 9‐anthracenemethanol. These products were prepared via a one‐pot synthesis in which a Diels‐Alder reaction occurred followed by an intramolecular transesterification to form the lactone ring. A key feature of this synthetic methodology is the straightforward purification of the reaction products, in most cases without the need for chromatography. The ease of work‐up along with the simple setup of the reaction (no catalysts or other reagents needed) make this methodology a convenient and potentially scalable route to complex, multicyclic structures. Molecular modeling of the transition structures for Diels‐Alder reaction suggested that transesterification could precede cycloaddition, but NMR in situ studies confirmed the opposite occurrence. Product formed exclusively in the trans configuration for all alkyl fumarates used.
Evaluation of Antioxidant and Antitrypanosomal Properties of a Selected Series of Synthetic 3‐Carboxamidocoumarins
Authors: Muñoz Andrea , Fonseca André , Matos Maria J. , Uriarte Eugenio , Santana Lourdes , Borges Fernanda , Figueroa Roberto , Olea Azar Claudio 
Published: September 2016

AbstractOxidative stress is involved in several parasitic diseases such as Chagas. Agents able to selectively modulate biochemical processes involved in the disease represent promising multifunctional agents for the delay or abolishment of the progression of this pathology. In the current work, differently substituted 3‐carboxamidocoumarins exerting both antioxidant and trypanocidal activities are described. Among the compounds synthesized, compound 3 (N‐(4‐hydroxyphenyl)coumarin‐3‐carboxamide) showed the most interesting antioxidant profile, presenting 53.2 % superoxide radical scavenging and the highest ORAC‐FL value (ORAC‐FL=1.87) of the series. In the trypanocidal study, compounds 9 (N‐(quinolin‐6‐yl)coumarin‐3‐carboxamide) and 10 (N‐(quinolin‐3‐yl)coumarin‐3‐carboxamide) presented high activity in epimastigote stage and low activity in trypomastigote stage, as well as low cytotoxic effects. Additionally, these compounds decreased mitochondrial transmembrane potential in epimastigote Dm28c. Based on these results, compounds 9 and 10 proved to be good candidates for further studies. Interestingly, the current study revealed that small structural changes in this scaffold allow modulating both activities, suggesting that these molecules present the desirable properties for the development of promising classes of antichagasic compounds.
Data and syntax centric anomaly detection for relational databases
Authors: Sallam Asmaa , Fadolalkarim Daren , Bertino Elisa , Xiao Qian 
Published: September 2016

Recent studies show that insider attacks that aim at exfiltrating data are very common and that these attacks are performed according to specific patterns. Protecting against such threats requires complementing existing security techniques, such as access control and encryption, with tools able to detect anomalies in data accesses. In this paper, we present a technique specifically tailored for detecting anomalous database accesses. Our technique extracts users’ access patterns based on both the syntax of the input queries and the amount of data in their output results. Our technique is based on miningSQLqueries in database audit logs in order to form profiles of the normal users’ access patterns. New queries are checked upon these profiles, and deviations from these profiles are considered anomalous and thus indicative of possible attempts to exfiltrate or misuse the data. Our technique works under two application scenarios. The first is when the database has role‐based access control (RBAC) in place. Under anRBACsystem, users belong to roles and privileges are associated with roles rather than individual users. For this scenario, we form profiles of roles which make our approach usable for database management systems(DBMSs)that have a large user population; in this scenario, we apply the naive Bayesian classifier which shows accurate results in practice. We also employ multilabeling classification to enhance accuracy when the access patterns are common to multiple roles. The second application scenario is when theDBMSdoes not applyRBAC. In this scenario, we apply theCOBWEBclustering method. Experimental results indicate that our techniques are very effective.WIREs Data Mining Knowl Discov2016, 6:231–239. doi: 10.1002/widm.1195This article is categorized under:Application Areas > Science and Technology
Bioproduction of riboflavin: a bright yellow history
Authors: Revuelta José Luis , Ledesma-Amaro Rodrigo , Lozano-Martinez Patricia , Díaz-Fernández David , Buey Rubén M , Jiménez Alberto 
Published: September 2016

AbstractRiboflavin (vitamin B2) is an essential nutrient for humans and animals that must be obtained from the diet. To ensure an optimal supply, riboflavin is used on a large scale as additive in the food and feed industries. Here, we describe a historical overview of the industrial process of riboflavin production starting from its discovery and the need to produce the vitamin in bulk at prices that would allow for their use in human and animal nutrition. Riboflavin was produced industrially by chemical synthesis for many decades. At present, the development of economical and eco-efficient fermentation processes, which are mainly based on Bacillus subtilis and Ashbya gossypii strains, has replaced the synthetic process at industrial scale. A detailed account is given of the development of the riboflavin overproducer strains as well as future prospects for its improvement.
Pathogenic variants in HTRA2 cause an early‐onset mitochondrial syndrome associated with 3‐methylglutaconic aciduria
Authors: Oláhová Monika , Thompson Kyle , Hardy Steven A. , Barbosa Inês A. , Besse Arnaud , Anagnostou Maria‐Eleni , White Kathryn , Davey Tracey , Simpson Michael A. , Champion Michael , Enns Greg , Schelley Susan , Lightowlers Robert N. , Chrzanowska‐Lightowlers Zofia M. A. , McFarland Robert , Deshpande Charu , Bonnen Penelope E. , Taylor Robert W. 
Published: September 2016

AbstractMitochondrial diseases collectively represent one of the most heterogeneous group of metabolic disorders. Symptoms can manifest at any age, presenting with isolated or multiple‐organ involvement. Advances in next‐generation sequencing strategies have greatly enhanced the diagnosis of patients with mitochondrial disease, particularly where a mitochondrial aetiology is strongly suspected yet OXPHOS activities in biopsied tissue samples appear normal. We used whole exome sequencing (WES) to identify the molecular basis of an early‐onset mitochondrial syndrome—pathogenic biallelic variants in the HTRA2 gene, encoding a mitochondria‐localised serine protease—in five subjects from two unrelated families characterised by seizures, neutropenia, hypotonia and cardio‐respiratory problems. A unifying feature in all affected children was 3‐methylglutaconic aciduria (3‐MGA‐uria), a common biochemical marker observed in some patients with mitochondrial dysfunction. Although functional studies of HTRA2 subjects’ fibroblasts and skeletal muscle homogenates showed severely decreased levels of mutant HTRA2 protein, the structural subunits and complexes of the mitochondrial respiratory chain appeared normal. We did detect a profound defect in OPA1 processing in HTRA2‐deficient fibroblasts, suggesting a role for HTRA2 in the regulation of mitochondrial dynamics and OPA1 proteolysis. In addition, investigated subject fibroblasts were more susceptible to apoptotic insults. Our data support recent studies that described important functions for HTRA2 in programmed cell death and confirm that patients with genetically‐unresolved 3‐MGA‐uria should be screened by WES with pathogenic variants in the HTRA2 gene prioritised for further analysis.
Perioperative Heat Loss Prevention‐A Feasibility Trial
Authors: Kurnat‐Thoma Emma L. , Roberts Mary M. , Corcoran Eleanor B. 
Published: September 2016

AbstractPreventing unplanned perioperative hypothermia is crucial. Thermal reflective blankets may reduce heat loss, promote normothermia, increase patient comfort, and decrease cotton blanket expenses. Our purpose was to determine whether a thermal reflective blanket plus one warmed cotton blanket provides better temperature control and thermal comfort than warmed cotton blankets only. We compared two groups of perioperative patients who received a thermal reflective blanket plus one warmed cotton blanket (n = 110) or warmed cotton blankets only (n = 114) for temperature control and comfort, and we evaluated outcomes in the preoperative holding area, the OR, and the postanesthesia care unit. There were no significant differences in patient temperature or comfort between groups. Use of thermal reflective blankets led to significantly reduced use of warmed cotton blankets (t209 = −10.51, P < .001), and a cost threshold for clinical adoption was identified. The hospital opted not to purchase thermal reflective blankets because of equivalent performance and minimal cost savings.
Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis
Authors: Proitsi Petroula , Kim Min , Whiley Luke , Simmons Andrew , Sattlecker Martina , Velayudhan Latha , Lupton Michelle K. , Soininen Hillka , Kloszewska Iwona , Mecocci Patrizia , Tsolaki Magda , Vellas Bruno , Lovestone Simon , Powell John F. , Dobson Richard J.B. , Legido-Quigley Cristina 
Published: September 2016

AbstractIntroductionThe aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex).MethodsWe performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods.ResultsWe replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R2 = 0.10, test data set) and brain atrophy (R2 ≥ 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines.DiscussionBlood lipids are promising AD biomarkers that may lead to new treatment strategies.
Amyloid tracers binding sites in autosomal dominant and sporadic Alzheimer's disease
Authors: Ni Ruiqing , Gillberg Per‐Göran , Bogdanovic Nenad , Viitanen Matti , Myllykangas Liisa , Nennesmo Inger , Långström Bengt , Nordberg Agneta 
Published: September 2016

IntroductionAmyloid imaging has been integrated into diagnostic criteria for Alzheimer's disease (AD). How amyloid tracers binding differ for different tracer structures and amyloid‐β aggregates in autosomal dominant AD (ADAD) and sporadic AD is unclear.MethodsBinding properties of different amyloid tracers were examined in brain homogenates from six ADAD with APPswe, PS1 M146V, and PS1 EΔ9 mutations, 13 sporadic AD, and 14 control cases.Results3H‐PIB, 3H‐florbetaben, 3H‐AZD2184, and BTA‐1 shared a high‐ and a varying low‐affinity binding site in the frontal cortex of sporadic AD. AZD2184 detected another binding site (affinity 33 nM) in the frontal cortex of ADAD. The 3H‐AZD2184 and 3H‐PIB binding were significantly higher in the striatum of ADAD compared to sporadic AD and control. Polyphenol resveratrol showed strongest inhibition on 3H‐AZD84 binding followed by 3H‐florbetaben and minimal on 3H‐PIB.DiscussionThis study implies amyloid tracers of different structures detect different sites on amyloid‐β fibrils or conformations.