bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC by intranasal administration of multiple escalating dose in healthy male subjects
Authors: Thennati Rajamannar , Khanna Aman , Khanna Mallika , Sonaiya Tushar , Mehta Tejas , Mehta Kalpana , Shahi Pradeep , Patel Jigneshkumar
Published: June 2014

A novel corticosteroid compound (short form of IUPAC name: SFDAC) has been discovered by Sun Pharma Advanced Research Company (SPARC) Ltd. A randomized, observer‐blind, active‐controlled, parallel‐groups, intranasal multiple escalating dose study was conducted in healthy male subjects to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of compound SFDAC formulated as an aqueous suspension for intranasal administration. Intranasal sprays of SFDAC, active control fluticasone propionate (FP) and placebo were administered once in a day for 14 days as per randomization. Various clinical evaluations including 24‐hour serum cortisol and urinary free cortisol (UFC) profiles were carried out. Blood samples were collected at pre‐defined time‐points and analyzed using a validated chromatographic method for estimation of SFDAC and its metabolite. The results of the study indicate that multiple dose of SFDAC intranasal spray upto 3,200 µg is safe and tolerated. Clinically significant suppression of hypothalamic pituitary adrenal (HPA) axis was not observed. The plasma concentration of SFDAC was found to be below the lower limit of quantification (LLQ) at most time‐points for all subjects. SFDAC M1 metabolite was detected only at picogram level in plasma. The safety and pharmacokinetic characteristics of SFDAC observed in this study support further clinical development of the SFDAC nasal spray.
Slide Fastener Reduction of Graphene‐Oxide Edges by Calcium: Insight from Ab Initio Molecular Dynamics
Authors: Xie Sheng‐Yi , Li Xian‐Bin , Tian Wei Quan , Wang Dan , Chen Nian‐Ke , Han Dong , Sun Hong‐Bo
Published: June 2014

The reduction of graphene oxide can be used as a simple way to produce graphene on a large scale. However, the numerous edges produced by the oxidation of graphite seriously degrade the quality of the graphene and its carrier transport property. In this work, the reduction of oxygen‐passivated graphene edges and the subsequent linking of separated graphene sheets by calcium are investigated by using first‐principles calculations. The calculations show that calcium can effectively remove the oxygen groups from two adjacent edges. The joining point of the edges serves as the starting point of the reduction and facilitates the reaction. Once the oxygen groups are removed, the crack is sutured. If the joining point is lacking, it becomes difficult to zip the separated fragments. A general electron‐reduction model and a random atom‐reduction model are suggested for these two situations. The present study sheds light on the reduction of graphene‐oxide edges by using reactive metals to give large‐sized graphene through a simple chemical reaction.
Enzymes in lipid modification: Past achievements and current trends
Authors: Bornscheuer Uwe T.
Published: June 2014

In this minireview, the application of enzymes for the modification of fats and oils is covered with special emphasis on lipase‐catalyzed synthesis of structured triglycerides. Furthermore, protein engineering methods to alter the fatty acid chain‐length or the trans‐fatty acid selectivity of lipase A from Candida antarctica and an enzymatic two‐step method to remove the contaminant 3‐monochloro‐1,2‐propane diol are presented. Also the combination of several enzymes enables cascade reactions to obtain products such as ω‐hydroxycarboxylic acids useful for oleochemistry and recently published achievements to produce valuable compounds by metabolic engineering of microorganisms as exemplified for PUFA or fatty acid esters starting from sugars as renewable resources are covered. Special emphasis is given on achievements made in the authors group.

This review highlights developments in the field of enzymatic lipid modification covering the use of commercial enzymes, the design of lipases via protein engineering as well as recently established enzyme cascade reactions and examples for metabolic engineering to yield fatty acids and their derivatives.
Neighbouring Group Participation During Glycosylation: Do 2‐Substituted Ethyl Ethers Participate?
Authors: Cox Daniel J. , Singh Govind P. , Watson Andrew J. A. , Fairbanks Antony J.
Published: June 2014

The development of new protecting groups that undergo neighbouring group participation (NGP) via six‐membered ring intermediates to promote the formation of α‐1,2‐cis glycosidic linkages complements the established use of 5‐ring NGP in terms of stereochemical outcome. A selection of glycosyl donors was synthesised that possessed novel 2‐iodo‐ and 2‐(phenylseleno)ethyl ether protecting groups in an attempt to promote highly α‐selective glycosylation by 6‐ring NGP. Although the fully armed donors produced α‐glucosides as the predominant reaction products, low‐temperature NMR studies did not show NGP by the observation of cyclised reaction intermediates. The corresponding disarmed glycosyl donors were unexpectedly less stereoselective. NMR spectroscopy revealed that the 2‐iodoethyl ether did not participate in any of the glycosylation processes; however, the 2‐(phenylseleno)ethyl ether did participate, and β‐configured cyclic intermediates were observed. The fact that considerable amounts of β‐glycoside product were formed in these latter cases indicated that the predominant reaction pathway to product did not occur through the observed cyclic species. Clearly, a fine balance exists during glycosylation reactions, and the reaction pathway to product depends on a variety of factors. Notably, the formation of cyclised intermediates by 6‐ring NGP is not on its own sufficient to ensure high levels of α‐stereoselectivity.
Detection of α‐Methylacyl‐CoA Racemase in Serum and Urine Using a Highly Sensitive Electrochemical Immunodetector
Authors: Wang Jiapeng , Yau Siu‐Tung
Published: June 2014

The detection of α‐methylacyl‐CoA racemase (AMACR), a novel biomarker for prostate cancer, is demonstrated in serum and urine using a novel immuno‐detection method. The detection system consists of a three‐electrode conventional electrochemical cell modified with a gating electrode for applying a gating voltage VG to the immune complex immobilized on the working electrode to provide signal amplification. The detection system is realized by integrating gating electrodes with screen‐printed electrodes. This detection method does not require involved sample preparation procedures. The detection was demonstrated in serum and urine samples on the nanogram/mL level with VG equal to 0.6 V. Detection in serum was also performed on the picogram/mL level with a limit of 100 picogram/mL with VG=0.6 V being a necessary condition.
Exergetic Approach to Investigate the Arrangement of Compressors of a Pipeline Boosting Station
Authors: Mohamadi‐Baghmolaei Mohamad , Tabkhi Firooz , Sargolzaei Javad
Published: June 2014

Different arrangements of variable‐speed turbo‐compressor units in a pipeline boosting station are investigated by estimating the exergy destruction and exergetic efficiency; a thermodynamic method for quantifying irreversibility. Fuel consumption is determined by using the performance curves of compressors and turbines that are unique for each turbo‐compressor. Exergy destruction values of eight possible configurations, including coolers, are estimated for a specific station and result in the following values: 2.932 kg s−1 fuel consumption, 132.13 MW exergy destruction, and 99.4 MW exergetic efficiency for the optimum configuration. The case study is focused on the transmission of sour gas through a 56 inch (1 inch=2.54 cm) pipeline. Corresponding state theory within a simple virial equation of state is used to determine the effect of H2S and CO2. The results show that the exergetic efficiency of each configuration depends on the operating conditions and number of compressors in use. The optimum configuration depends on the station delivery flow rate and its compression ratio.
Automated recognition of quasi‐planar ignimbrite sheets as paleosurfaces via robust segmentation of digital elevation models: an example from the Central Andes
Authors: Székely Balázs , Koma Zsófia , Karátson Dávid , Dorninger Peter , Wörner Gerhard , Brandmeier Melanie , Nothegger Clemens
Published: June 2014

Quasi‐planar morphological surfaces may become dissected or degraded with time, but still retain original features related to their geologic‐geomorphic origin. To decipher the information hidden in the relief, recognition of such features is required, possibly in an automated manner. In our study, using Shuttle Radar Topography Mission (SRTM) digital elevation model (DEM), an existing algorithm has been adapted to recognize quasi‐planar features fulfilling specified criteria. The method has been applied to a study area of the Central Andes with Miocene to Quaternary volcanic edifices, tilted ignimbrite surfaces, and basin‐filling sediments. The result is a surface segmentation, whereas non‐planar features (gullies, tectonic faults, etc.) are sorted out. The main types of geomorphic features that can be distinguished and interpreted are as follows. (1) The west‐dipping western margin of the Altiplano is differentiated into segments of the lower sedimentary cover that of increased erosion by tectonic steepening at intermediate levels, and an upper plane with limited erosion. (2) In the central part of the Western Cordillera, the Oxaya ignimbrite block shows a ‘striped’ bulging pattern that results from a smoothly changing surface dip. This pattern is due to continuous folding/warping of the ignimbrite block possibly related to gravitational movements. (3) To the west, large, uniform planes correspond to flat, smooth, tectonically undisturbed surfaces of young sedimentary cover of the Central Basin. (4) The evolution of Taapaca volcanoes with sector collapse events and cone‐building phases is shown by several segments with overlapping clastic aprons. (5) To the east, on the western margin of the Altiplano, young intermontane basins filled by Upper Miocene sediments show progressively increasing dip toward basin margins, reflected by a circular pattern of the segmentation planes. We show that the segmentation models provide meaningful images and additional information for geomorphometric analysis that can be interpreted in terms of geological and surface evolution models. Copyright © 2014 John Wiley & Sons, Ltd.
Chromium resistance of dandelion (Taraxacum platypecidum Diels.) and bermudagrass (Cynodon dactylon [Linn.] Pers.) is enhanced by arbuscular mycorrhiza in Cr(VI)-contaminated soils
Authors: Wu Song-Lin , Chen Bao-Dong , Sun Yu-Qing , Ren Bai-Hui , Zhang Xin , Wang You-Shan
Published: June 2014

In a greenhouse pot experiment, dandelion (Taraxacum platypecidum Diels.) and bermudagrass (Cynodon dactylon[Linn.] Pers.), inoculated with and without arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis, were grown in chromium (Cr)-amended soils (0 mg/kg, 5 mg/kg, 10 mg/kg, and 20 mg/kg Cr[VI]) to test whether arbuscular mycorrhizal (AM) symbiosis can improve Cr tolerance in different plant species. The experimental results indicated that the dry weights of both plant species were dramatically increased by AM symbiosis. Mycorrhizal colonization increased plant P concentrations and decreased Cr concentrations and Cr translocation from roots to shoots for dandelion; in contrast, mycorrhizal colonization decreased plant Cr concentrations without improvement of P nutrition in bermudagrass. Chromium speciation analysis revealed that AM symbiosis potentially altered Cr species and bioavailability in the rhizosphere. The study confirmed the protective effects of AMF on host plants under Cr contaminations. Environ Toxicol Chem 2014; 33:2105–2113. © 2014 SETAC
Disassociation of verbal learning and hippocampal volume in type 2 diabetes and major depression
Authors: Ajilore O. , Lamar M. , Medina J. , Watari K. , Elderkin‐Thompson V. , Kumar A.
Published: June 2014

Objective

The purpose of this study was to examine the relationship between verbal learning and memory performance and hippocampal volume in subjects with co‐morbid type 2 diabetes and major depression compared with healthy control subjects and subjects with type 2 diabetes alone.

Methods

Twenty four subjects with type 2 diabetes and 20 subjects with type 2 diabetes and major depression were recruited from endocrinology clinics and were compared with 32 healthy control subjects recruited from the community. Subjects were scanned on a 1.5 T GE scanner, and hippocampal volumes were measured using Freesurfer. The California Verbal Learning Test assessed learning and memory. Significant predictors of verbal learning performance (e.g., age, gender, education, blood pressure, stroke risk, hemoglobin A1c, and hippocampal volume) were determined using a stepwise linear regression.

Results

Subjects with diabetes and depression had significantly worse performance on verbal list learning compared with healthy control subjects. Hippocampal volume was a strong predictor of performance in healthy control subjects, and age and hippocampal volume were strong predictors in subjects with type 2 diabetes alone. Age alone was a significant predictor of verbal learning performance in subjects with diabetes and depression.

Conclusions

The relationship between hippocampal volume and performance on the California Verbal Learning Test is decoupled in subjects with type 2 diabetes and major depression and this decoupling may contribute to poor verbal learning and memory performance in this study population. Copyright © 2014 John Wiley & Sons, Ltd.
The relationship between changes in quality of life outcomes and progression of Alzheimer's disease: results from the Dependence in AD in England 2 longitudinal study
Authors: Trigg Richard , Jones Roy W. , Knapp Martin , King Derek , Lacey Loretto A. ,   for the DADE‐2 Investigator Groups
Published: June 2014

Objective

The relationship between conventional indicators of Alzheimer's disease (AD) progression and quality of life (QoL) outcomes is unclear. Dependence on others has been recommended as a unifying construct in defining AD severity. This study examined the relationship between indicators of disease severity (including dependence) and changes in QoL and utility over 18 months.

Methods

A multi‐centre, cohort study was conducted across 18 UK sites. One hundred and forty‐five patients with possible/probable AD and their caregivers completed assessments of disease severity (Dependence Scale, Mini‐mental state examination, Neuropsychiatric Inventory, Disability Assessment for Dementia), dementia‐specific QoL (DEMQOL, DEMQOL‐Proxy) and generic health‐related utility (EQ‐5D) at both time points.

Results

There was evidence of individual change in QoL over 18 months, with over 50% of patients reporting either maintenance or improvement of life quality. The EQ‐5D proxy suggested a mean decline in QoL, whereas the DEMQOL‐Proxy indicated overall improvement. In the subsample of people who self‐reported QoL and utility, no mean change was evident. Changes in dependence did not explain changes on any QoL or utility outcome. There was a weak association between the EQ‐5D proxy and changes in cognition, whereas changes on the DEMQOL‐Proxy were partly explained by changes in behavioural disturbance.

Conclusions

The natural progression of AD over 18 months does not lead to inevitable decline in QoL or utility. There are no clear or consistent direct relationships between changes in disease severity and QoL outcomes. The impact of increasing dependence and worsening disease severity is likely buffered by a combination of psychological, social and environmental factors. Copyright © 2014 John Wiley & Sons, Ltd.
The clock drawing test, mortality, incident cardiovascular events and dementia
Authors: Peters Ruth , Beckett Nigel , Pereira Lisa , Poulter Ruth , Pinto Elisabete , Ma Shuping , Dumitrascu Dan , Barrowdale Daniel , Butler Michael , Fletcher Astrid , Bulpitt Christopher
Published: June 2014

Objective

The purpose of this study is to examine the association of the clock drawing test (CDT) with incident dementia, cardiovascular events and mortality in very elderly hypertensive patients.

Method

All participants were hypertensive and aged 80 years and over. The CDT was administered at baseline and annually thereafter. Data on incident cardiovascular, fatal events and dementia were collected over follow‐up.

Results

There were 3845 participants recruited and followed up for a mean of 2.1 years. Of these, 2701 completed a CDT with 2259 available at baseline. Of this group, 6.6% had a cardiovascular event, 6.1% died, and 10% were diagnosed with dementia. There was no relationship between baseline CDT score and subsequent cardiovascular events or mortality. For incident dementia, the hazard ratio was 0.88 (95% confidence intervals 0.83–0.94) suggesting that better performance on the baseline CDT was associated with a lower risk of dementia.

Conclusion

These results provide tentative support for the CDT alongside other cognitive screening tools in a hypertensive elderly population. Copyright © 2014 John Wiley & Sons, Ltd.
Charge‐Transfer Complexes of Conjugated Polymers
Authors: Sosorev Andrey Yu. , Paraschuk Dmitry Yu.
Published: June 2014

Donoracceptor blends of conjugated polymers (CPs) are workhorse materials for the state‐of‐the‐art polymer solar cells. Although earlier it was suggested that charge transfer in these blends occurred only in the excited electronic state, a body of evidence for ground‐state charge transfer and the corresponding charge‐transfer complex (CTC) formation has been reported in the last decade. In some CP:acceptor blends, the CTC is pronounced and can be noticed visually as a colour change, while in more common CP:fullerene blends it is very weak. However, in both, the CTC governs charge separation, which is the key photophysical process for organic solar cells, through so‐called charge‐transfer states. Moreover, the pronounced CTC can substantially modify the blend properties: extend the blend absorption in the red and infrared regions, change the morphology to facilitate donoracceptor intermixing, stimulate polymer self‐organization and ordering, and increase the polymer photooxidation stability. Addition of one of the strongest organic acceptors, 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane (F4‐TCNQ), to the CP:fullerene blend is an example of organic doping (a CTC with full charge transfer), improving the blend structural and electronic properties and finally the solar cell performance. In this review, we summarize the current knowledge on CTCs in various CP:acceptor blends and the impact of CTC on the blend properties and the device performance.
DESIGNING AN IF–THEN RULES‐BASED ENSEMBLE OF HETEROGENEOUS BANKRUPTCY CLASSIFIERS: A GENETIC ALGORITHM APPROACH
Authors: Davalos Sergio , Leng Fei , Feroz Ehsan H. , Cao Zhiyan
Published: June 2014

This paper proposes a framework for an ensemble bankruptcy classifier that uses if–then rules to combine the outputs from a heterogeneous set of classifiers. A genetic algorithm (GA) induces the rules using an asymmetric, cost‐sensitive fitness function that includes accuracy and misclassification costs. The GA‐based ensemble classifier outperforms individual classifiers and ensemble classifiers generated by other methods. The results of the classifier are in the form of if–then rules. We apply the approach to a balanced dataset and an imbalanced dataset. Both are composed of firms subject to financial distress and cited in the US Securities and Exchange Commission's Accounting and Auditing Enforcement Releases. Copyright © 2014 John Wiley & Sons, Ltd.
Surface modification of SU‐8 for enhanced cell attachment and proliferation within microfluidic chips
Authors: Hamid Qudus , Wang Chengyang , Snyder Jessica , Sun Wei
Published: June 2014

Advances in micro‐electro‐mechanical systems (MEMS) have led to an increased fabrication of micro‐channels. Microfabrication techniques are utilized to develop microfluidic channels for continuous nutrition supply to cells inside a micro‐environment. The ability of cells to build tissues and maintain tissue‐specific functions depends on the interaction between cells and the extracellular matrix (ECM). SU‐8 is a popular photosensitive epoxy‐based polymer in MEMS. The patterning of bare SU‐8 alone does not provide the appropriate ECM necessary to develop microsystems for biological applications. Manipulating the chemical composition of SU‐8 will enhance the biological compatibility, giving the fabricated constructs the appropriate ECM needed to promote a functional tissue array. This article investigates three frequently used surface treatment techniques: (1) plasma treatment, (2) chemical reaction, and (3) deposition treatment to determine which surface treatment is the most beneficial for enhancing the biological properties of SU‐8. The investigations presented in this article demonstrated that the plasma, gelatin, and sulfuric acid treatments have a potential to enhance SU‐8's surface for biological application. Of course each treatment has their advantages and disadvantages (application dependent). Cell proliferation was studied with the use of the dye Almar Blue, and a micro‐plate reader. After 14 days, cell proliferation to plasma treated surfaces was statistically significantly enhanced (p < 0.00001), compared to untreated surfaces. The plasma treated surface is suggested to be the better of the three treatments for biological enhancement followed by gelatin and sulfuric acid treatments, respectively. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 473–484, 2015.
Rapid Skeletal Turnover in a Radiographic Mimic of Osteopetrosis
Authors: Whyte Michael P , Madson Katherine L , Mumm Steven , McAlister William H , Novack Deborah V , Blair Jo C , Helliwell Timothy R , Stolina Marina , Abernethy Laurence J , Shaw Nicholas J
Published: June 2014

Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover, leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis (OPT), but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was >5000 IU/L (normal <850 IU/L). After partial resection, the granuloma re-grew but then regressed and stabilized during 3 years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished, but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, bone mineral density (BMD) Z-scores reached +9.1 and +5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of lipoprotein receptor-related protein 4 (LRP4), LRP5, or TGFβ1, and for defective sclerostin (SOST), osteoprotegerin (OPG), RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his nonconsanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown. © 2014 American Society for Bone and Mineral Research.
Bay‐type H···H “bonding” in cis‐2‐butene and related species: QTAIM versus NBO description
Authors: Weinhold Frank , Schleyer Paul von Ragué , McKee William Chadwick
Published: June 2014

We use comparative natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) methods to analyze the proximal bay‐type H···H interactions in cis‐2‐butene and related species, which lead to controversial interpretation as attractive “HH bonding” in the QTAIM framework. We address the challenging questions concerning well established structural, conformational, and vibrational properties of such species that appear to be sharply at odds with the QTAIM interpretation. In contrast to the purported “HH bonding” of QTAIM theory, NBO‐based evaluation of steric (donor–donor) and hyperconjugative (donor–acceptor) interactions unambiguously portrays such H···H contacts as dominated by steric clashes that are only partially softened by weak secondary hyperconjugative interactions, contributing negligibly (bHH < 0.01) to H···H bond order. Additional details of NBO‐based versus QTAIM‐based description are provided by natural bond critical point analysis of topological bond critical point properties, which further emphasizes the contrast between the problematic bay‐type H···H contacts and remaining noncontroversial (consensus) chemical bonds. NBO analysis is thereby shown to be fully consistent with the traditional physical organic concept of repulsive bay‐type H···H contacts, including the corollary array of structural, conformational, and vibrational properties. © 2014 Wiley Periodicals, Inc.
Implicit treatment of solvent dispersion forces in protein simulations
Authors: Hassan Sergio A.
Published: June 2014

A model is proposed for the evaluation of dispersive forces in a continuum solvent representation for use in large‐scale computer simulations. The model captures the short‐ and long‐range effects of water‐exclusion in conditions of partial and anisotropic hydration. The model introduces three parameters, one of which represents the degree of hydration (water occupancy) at any point in the system, which depends on the solute conformation, and two that represent the strength of water–water and water–solute dispersive interactions. The model is optimized for proteins, using hydration data of a suboptimally hydrated binding site and results from dynamics simulations in explicit water. The model is applied to a series of aliphatic‐alcohol/protein complexes and a set of binary and ternary complexes of various sizes. Implications for weak and ultra‐weak protein‐protein association and for simulation in crowded media are discussed. Published 2014. This article is a U.S. Government work and is in the public domain in the USA
New Synthesis of 3,6‐Dibromophthalonitrile and Phthalocyanine Having Eight Thienyl Substituents at Peripheral α‐Positions
Authors: Wang Rongrong , Zhao Yan , Zhu Chunli , Huang Xuebin
Published: June 2014

3,6‐Dibromophthalonitrile was successfully synthesized from 3,6‐dihydroxyphthalonitrile using triphenylphosphine dibromide as bromation reagent. Starting from 3,6‐dibromophthalonitrile, synthesis of 1,4,8,11,15,18,22,25‐octakis(4‐dodecylthiophen‐2‐yl)phthalocyaninatozinc(II) (ZnPc) was described. TGA demonstrated the perfect stability of ZnPc. The newly prepared ZnPc that was symmetrically substituted with thienyl substituents results in an intensively red‐shifted Q‐band. The HOMO and LUMO values of ZnPc were acquired by CV.
An Efficient Synthesis of Polyfunctionalized Indole Derivatives via Three‐component Domino Reaction Catalyzed by L‐Proline
Authors: Fu Lei , Lin Wei , Huang Zhi‐Bin , Shi Da‐Qing
Published: June 2014

A facile and efficient one‐pot procedure for the preparation of indeno[1,2‐b]indole derivatives via three‐component domino reaction of ninhydrin, enaminones, and malononitrile catalyzed by L‐proline is described. In this reaction, two rings and four bonds were formed by one‐pot.
N‐Arylation of Heterocycles Promoted by Cyclen Derivatives
Authors: Zhang Bao‐Hua , Shi Lan‐xiang , Liu Si‐Jie , Guo Rui‐Xia
Published: June 2014

An efficient copper‐catalyzed N‐arylation reactions of imidazole, indole, and triazole with aryl or heteroaryl halides using cyclen derivatives as efficient organic base and ligand at moderate temperature have been investigated. The cross‐couplings proceed smoothly with good to excellent yields.
Disulfide linkage Raman markers: a reconsideration attempt
Authors: Hernández Belén , Pflüger Fernando , López‐Tobar Eduardo , Kruglik Sergei G. , Garcia‐Ramos José V. , Sanchez‐Cortes Santiago , Ghomi Mahmoud
Published: June 2014

During the last decades, Raman spectroscopy has been routinely used for probing the conformational features of disulfide linkages in peptides and proteins. However, the interpretation of disulfide Raman markers is currently performed by a simple rule derived from the earliest observations on dialkyl disulfides. More precisely, this rule consists of the following: (1) in analyzing the Raman bands in the 550–500 cm−1 region ascribed to disulfide bond stretch motion, namely, ν(S‐S), and (2) assigning the three types of Raman markers observed at ~500, ~520, and ~540 cm−1 to three families of rotamers defined along the three successive bonds of the ‐C‐S‐S‐C‐ moiety, referred to as ggg, ggt, and tgt. In this report, we attempt to show that an accurate analysis of disulfide vibrational features needs the use of the five torsion angles (χ1, χ2, χ3, χ2', and χ1') along the five successive bonds joining the two α‐carbon atoms in the cystine (Cys‐Cys) unit. The present work is inspired by the disulfide conformational investigations performed by a statistical scan of numerous protein crystal and nuclear magnetic resonance data, taking into account the handedness (right and left) of a disulfide bridge, its spatial shape (Staple, Hook, and Spiral), as well as the signs of the two extreme torsion angles χ1 and χ1'. It appears that the combined use of the old and recent conformational notations allows a more accurate structural and vibrational analysis of disulfide linkage. Copyright © 2014 John Wiley & Sons, Ltd.
Changes in the rheological properties of wheat dough during short‐term storage of wheat
Authors: Hadnađev Miroslav , Dapčević Hadnađev Tamara , Pojić Milica , Torbica Aleksandra , Tomić Jelena , Rakita Slađana , Janić Hajnal Elizabet
Published: June 2014

BACKGROUND

The aim of the present study was to investigate the ability of the small‐ and large‐deformation fundamental rheological tests to monitor the changes during short‐term post‐harvest storage of wheat.

RESULTS

At the end of wheat storage period, wet gluten quantity decreased, while gluten index increased in comparison to those of freshly harvested samples. The rheological properties of dough changed over the pre‐defined period of storage in terms of becoming more elastic and less extensible in comparison to that of freshly harvested wheat. Visco‐elastic properties of weaker flour samples changed more markedly during storage than those of stronger flours, indicating that the intensity of dough rheological changes during wheat storage might be dependent on gluten quality and were the characteristic of wheat variety.

CONCLUSION

It was shown that small deformation dynamic oscillation and large deformation creep‐recovery tests can be successfully employed to monitor the changes in flour quality during wheat storage and that required storage period after wheat harvesting has to be defined according to wheat variety initial rheological properties and its gluten quality. © 2014 Society of Chemical Industry
BDNF Val66Met polymorphism in primary adult‐onset dystonia: A case‐control study and meta‐analysis
Authors: Gómez‐Garre Pilar , Huertas‐Fernández Ismael , Cáceres‐Redondo María Teresa , Alonso‐Canovas Araceli , Bernal‐Bernal Inmaculada , Blanco‐Ollero Alberto , Bonilla‐Toribio Marta , Burguera Juan Andrés , Carballo Manuel , Carrillo Fátima , Catalán‐Alonso María José , Escamilla‐Sevilla Francisco , Espinosa‐Rosso Raúl , Fernández‐Moreno María Carmen , García‐Caldentey Juan , García‐Moreno José Manuel , García‐Ruiz Pedro José , Giacometti‐Silveira Sandra , Gutiérrez‐García Javier , Jesús Silvia , López‐Valdés Eva , Martínez‐Castrillo Juan Carlos , Martínez‐Torres Irene , Medialdea‐Natera María Pilar , Méndez‐Lucena Carolina , Mínguez‐Castellanos Adolfo , Moya Miguel , Ochoa‐Sepulveda Juan José , Ojea Tomás , Rodríguez Nuria , Sillero‐Sánchez Miriam , Vargas‐González Laura , Mir Pablo
Published: June 2014

Background

A polymorphism in brain‐derived neurotrophic factor (BDNF) (Val66Met) has been reported as a risk factor in primary dystonia. However, overall the results have been inconclusive. Our aim was to clarify the association of Val66Met with primary dystonia, and with the most prevalent clinical subtypes, cervical dystonia and blepharospasm.

Methods

We conducted a Spanish multicenter case‐control study (including 680 primary dystonia patients and 788 healthy controls) and performed a meta‐analysis integrating our study and six previously published studies (including a total of 1,936 primary dystonia patients and 2,519 healthy controls).

Results

We found no allelic or genotypic association with primary dystonia, cervical dystonia, or blepharospasm risks, for the allele A (Met) from a BDNF Val66Met polymorphism in our case‐control study. This was confirmed by results from our meta‐analysis in white and mixed ethnic populations in any genetic model.

Conclusion

We did not find any evidence supporting the association of the BDNF Val66Met polymorphism with primary dystonia. © 2014 International Parkinson and Movement Disorder Society
An iterative method for backward time‐fractional diffusion problem
Authors: Wang Jun‐Gang , Wei Ting
Published: June 2014

The aim of this work is to solve the backward problem for a time‐fractional diffusion equation with variable coefficients in a general bounded domain. The problem is ill‐posed in L
2 norm sense. An iteration scheme is proposed to obtain a regularized solution. Two kinds of convergence rates are obtained using an a priori regularization parameter choice rule and an a posteriori regularization parameter choice rule. Numerical examples in one‐dimensional and two‐dimensional cases are provided to show the effectiveness of the proposed methods. © 2014 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 30: 2029–2041, 2014
Misclassification in assessment of diabetogenic risk using electronic health records
Authors: Winterstein Almut G. , Kubilis Paul , Bird Steve , Cooper‐DeHoff Rhonda M. , Nichols Greg A. , Delaney Joseph A.
Published: June 2014

Purpose

Suspected diabetogenic effects or drug indication may increase testing for diabetes mellitus (DM), resulting in measurement bias when evaluating diabetogenic drug effects. We sought to evaluate the validity of electronic health record data in determining DM risk.

Methods

We used time‐dependent Cox proportional hazard models within a retrospective cohort design to assess associations between use of antihypertensives, statins, atypical antipsychotics, and antidepressants, and two endpoints: (i) DM onset defined as fasting blood glucose (BG) ≥126 mg/dl, random BG ≥200 mg/dl, HbA1c ≥7.0%, or antidiabetic drug initiation; and (ii) first negative DM test. We used Poisson regression to assess the influence of these drugs on DM testing rates. Patients aged 35–64 years enrolled in Kaiser Permanente Northwest between 1997 and 2010 entered the cohort at the first negative BG test after ≥6 months without manifest DM.

Results

All drug classes showed significant associations not only with DM onset but also with first negative BG test and with DM testing rates. Antipsychotics had the greatest diabetogenic risk (adjusted hazard ratio [HR] = 1.73 [1.44–2.08]), the greatest propensity for a first negative test (adjusted HR = 1.87 [1.74–2.01]), and the highest testing rate (adjusted rate ratio = 1.76 [1.72–1.81]. Although renin–angiotensin system blockers and calcium channel blockers have shown no diabetogenic risk in clinical trials, both were associated with DM (HR = 1.19 [1.12–1.26] and 1.27 [1.17–1.38]), a negative glucose test (1.38 [1.35–1.41] and 1.24 [1.20–1.28]), and increased testing rates (rate ratio = 1.26 [1.24–1.27] and 1.27 [1.25–1.28]).

Conclusion

Caution should be used when diabetogenic risk is evaluated using data that rely on DM testing in general practice. Copyright © 2014 John Wiley & Sons, Ltd.
Development and performance evaluation of an ultralow flow nanoliquid chromatography‐tandem mass spectrometry set‐up
Authors: Köcher Thomas , Pichler Peter , De Pra Mauro , Rieux Laurent , Swart Remco , Mechtler Karl
Published: June 2014

LC‐MS/MS is the most commonly used technique for the identification and characterization of proteins. The efficiency of the electrospray process is a critical factor in LC‐MS/MS. Despite the benefits associated with very low flow rates for the ionization efficiency, most LC‐MS/MS platforms are operated at relatively high flow rates. The purpose of this work was to develop a nano LC system operable at a flow rate of 20 nL/min, applicable for routine analysis in proteomics laboratories. Peptide separation was performed with an analytical column packed with 2 μm porous chromatographic beads, a length of 25 cm and an inner diameter (i.d.) of 25 μm. Practical usability, reproducibility, and overall performance of the system were evaluated with a tryptic peptide mixture generated from HeLa cells. Using 100 ng of sample, we identified on average 3721 protein groups based on 25,699 peptides. We demonstrate that the number of peptides identified with this system increases with decreasing flow rates. Probing the sensitivity of the set‐up we analyzed only 10 ng of the sample, identifying an average number of 2042 protein groups based on 11 424 peptides. All MS data have been deposited in the ProteomeXchange with identifier PXD000396 (http://proteomecentral.proteomexchange.org/dataset/PXD000396).
An Efficient and Specific Protection of Non‐Thermal Plasma‐Induced Live Yeast Cell Derivative (LYCD) for Cells against Plasma Damage
Authors: Ma Ruonan , Feng Hongqing , Guo Jinsong , Liang Yongdong , Zhang Qian , Tian Ying , Zhang Jue , Fang Jing
Published: June 2014

With the development of plasma medicine, safety issues are emerging as a serious concern. In this study, the protective effects of live yeast cell derivative (LYCD) on yeast (Saccharomyces cerevisiae) and mammalian cells (NIH‐3T3) subjected to plasma treatment were investigated. The anti‐oxidative properties of LYCD were assessed by analyzing three important antioxidants: superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). The results show that LYCD can efficiently protect theS. cerevisiaeand NIH‐3T3 cells against plasma treatment by elevating the survival ratio from 7 to 60% and 10 to 60%, respectively, and reverse the increased intracellular reactive oxygen species production following plasma exposure. Additionally, the protection is shown to be specific when compared with UV and H2O2treatment. SOD and CAT activities as well as GSH content of LYCD increase linearly with plasma induction time. Simultaneously, the LYCD protection efficacies are increasing with longer plasma induction time, indicating that SOD, CAT, and GSH all contribute to the protective effect of LYCD. This work suggests that the non‐toxic LYCD can serve as a promising precaution agent to enhance the safety of plasma applied directly to human body in the future.
Cardiac extracellular proteome profiling and membrane topology analysis using glycoproteomics
Authors: Tian Yuan , Koganti Tejaswi , Yao Zhihao , Cannon Presley , Shah Punit , Pietrovito Laura , Modesti Alessandra , Aiyetan Paul , DeLeon‐Pennell Kristine , Ma Yonggang , Halade Ganesh V. , Hicks Chindo , Zhang Hui , Lindsey Merry L.
Published: June 2014

Purpose

Extracellular proteins are easily accessible, which presents a subproteome of molecular targets that have high diagnostic and therapeutic potential. Efforts have been made to catalog the cardiac extracellular matridome and analyze the topology of identified proteins for the design of therapeutic targets. Although many bioinformatics tools have been developed to predict protein topology, topology has been experimentally validated for only a very small portion of membrane proteins. The aim of this study was to use a glycoproteomics and MS approach to identify glycoproteins in the extracellular matridome of the infarcted left ventricle (LV) and provide experimental evidence for topological determination.

Experimental design

Glycoproteomics analysis was performed on eight biological replicates of LV samples from wild‐type mice at 7 days following myocardial infarction using SPE of glycopeptides, followed by mass spectrometric identification of N‐linked glycosylation sites for topology assessment.

Results

We identified hundreds of glycoproteins, and the identified N‐glycosylation sites provide novel information on the correct topology for membrane proteins present in the infarct setting.

Conclusions and clinical relevance

Our data provide the foundation for future studies of the LV infarct extracellular matridome, which may facilitate the discovery of drug targets and biomarkers.
Autophagy Activation and Antiviral Activity by a Licorice Triterpene
Authors: Laconi Samuela , Madeddu Maria A. , Pompei Raffaello
Published: June 2014

The triterpene glycyrrhizic acid (GRA), the main product from the Glycyrrhiza glabra medicinal plant, is known for its antiinflammatory and antimicrobial activity. In this work, GRA was studied for its ability to induce the autophagic process activator Beclin 1 in epithelial cells and to observe how this property could influence its antiviral activity. After 24 h of treatment, GRA induced a Beclin 1 production that was more than twofold higher than that produced by rapamycin, used as a reference compound. When the compounds were added to HeLa cells together with the viruses, GRA demonstrated a strong antiherpes simplex virus type 1 (HSV1) activity, whereas rapamycin had no activity. However, if the compounds were added to the cells 24 h before the viruses, GRA induced the production of an even higher amount of Beclin 1 and showed an improved antiviral effect; under these conditions, rapamycin was also able to exert a significant anti‐HSV1 activity. In conclusion, GRA is a strong inducer of the autophagy activator Beclin 1, which establishes a resistance state to HSV1 replication. Copyright © 2014 John Wiley & Sons, Ltd.
Synoptic versus orographic control on stationary convective banding
Authors: Barrett Andrew I. , Gray Suzanne L. , Kirshbaum Daniel J. , Roberts Nigel M. , Schultz David M. , Fairman Jonathan G.
Published: June 2014

Quasi‐stationary convective bands can cause large localised rainfall accumulations and are often anchored by topographic features. Here, the predictability of and mechanisms causing one such band are determined using ensembles of the Met Office Unified Model at convection‐permitting resolution (1.5 km grid length). The band was stationary over the UK for 3 h and produced rainfall accumulations of up to 34 mm. The amount and location of the predicted rainfall was highly variable despite only small differences between the large‐scale conditions of the ensemble members. Only three of 21 members of the control ensemble produced a stationary rain band; these three had the weakest upstream winds and hence lowest Froude number. Band formation was due to the superposition of two processes: lee‐side convergence resulting from flow around an upstream obstacle and thermally forced convergence resulting from elevated heating over the upstream terrain. Both mechanisms were enhanced when the Froude number was lower. By increasing the terrain height (thus reducing the Froude number), the band became more predictable.

An ensemble approach is required to successfully predict the possible occurrence of such quasi‐stationary convective events because the rainfall variability is largely modulated by small variations of the large‐scale flow. However, high‐resolution models are required to accurately resolve the small‐scale interactions of the flow with the topography upon which the band formation depends. Thus, although topography provides some predictability, the quasi‐stationary convective bands anchored by it are likely to remain a forecasting challenge for many years to come.
Robust Monitoring of an Industrial IT System in the Presence of Structural Change
Authors: Padonou Esperan , Roustant Olivier , Lutz Michel
Published: June 2014

This paper presents original research initiated by the monitoring needs of a semiconductor production plant. The industrial operations rely on an Information Technology (IT) system, and several time series data are controlled statistically. Unfortunately, these variables often contain outliers, as well as structural changes because of external decisions in the IT activity. As a consequence, it has been observed that the monitoring results obtained with standard techniques could be severely biased.

This paper attempts to overcome such difficulties. A new monitoring method is proposed, based on robust Holt–Winters smoothing algorithm, and coupled with a relearning procedure for structural break detection. Such a method is flexible enough for a large‐scale industrial application. We evaluate performance through simulation and show its usefulness in real industrial applications for univariate and multivariate time series. The scope of application deals with IT activity monitoring, but the introduced statistical methods are generic enough for being used in other industrial fields. Copyright © 2014 John Wiley & Sons, Ltd.
Examination of fragment ions of polystyrene in TOF‐SIMS spectra using MS/MS
Authors: Kawashima Tomoko , Kurosawa Takako , Aoyagi Satoka , Sheraz (née Rabbani) Sadia , Fletcher John S. , Futigami Masayo , Lockyer Nicholas P. , Vickerman John C.
Published: June 2014

In this study, tendencies of ionization and cleavage processes of time‐of‐flight (TOF)‐SIMS were examined using MS/MS, which enables an easy qualitative analysis of organic matters, to clarify the fragment ions showing structures of the organic materials. In this paper, a result of reviewing fragment ions in TOF‐SIMS spectra for polystyrene (PS) as the representative material is shown. Samples were measured with collision induced dissociation (CID)‐MS/MS of 1200 L (Varian Inc., USA) and TOF‐SIMS J105 (Ionoptika Ltd, UK) for the examination of fragment ions of the PS in TOF‐SIMS spectra. The use of CID MS/MS with a wide range of energy distribution is effective for the study of the ionization and cleavage process of TOF‐SIMS. As a result, the fragment ions representing the PS structure were clarified, which is useful for the material definition. The qualitative analysis was also applied to the fragment ions particularly obtained in this examination. It is suggested that the examination of the fragmentation process using MS/MS is useful for the mass spectra analysis of organic materials in TOF‐SIMS. Copyright © 2014 John Wiley & Sons, Ltd.
New approach for simulation of large cluster impact using smoothed particle hydrodynamics method
Authors: Lee Jong Wan
Published: June 2014

Using large‐scale atomistic simulations, it has been shown that the macroscopic cratering behavior emerges for projectile impacts on Au at projectile sizes between 1000 and 10 000 Au atoms at impact velocities comparable to typical meteoroid velocities. This indicates that the continuum model‐like fluid can be a possible candidate for the physical model of large cluster sputtering. Smoothed particle hydrodynamics (SPH) is a mesh‐free particle method for obtaining approximate numerical solutions of the equations of fluid dynamics by replacing the fluid with a set of particles. In this work, SPH has been introduced for the first time as an alternative but macroscopic thus quick method for the computer simulation of large cluster impact. It has been demonstrated that cratering process can be observed at the impact simulation of water cluster on water target. The SPH simulation can be applied after improvements in physical models and algorithms to investigate the sputtering effect on solid target using water cluster primary ion beams. Copyright © 2014 John Wiley & Sons, Ltd.