bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Tumor Necrosis Factor α Blockers in Early Axial Spondyloarthritis: Data From the DESIR Cohort
Authors: Moltó Anna , Paternotte Simon , Claudepierre Pascal , Breban Maxime , Dougados Maxime
Published: March 2014

Objective

To estimate the frequency of use and effectiveness in daily practice of tumor necrosis factor α (TNFα) blockers in a population with inflammatory back pain suggestive of early axial spondyloarthritis (SpA).

Methods

The Devenir des Spondylarthropathies Indifférenciées Récentes (DESIR) cohort is a prospective, multicenter, observational cohort of 708 patients with early (<3 years' duration) inflammatory back pain suggestive of axial SpA. The percentage of patients receiving TNFα blockers over the first 2 years of followup was estimated by survival analysis. To evaluate effectiveness, the primary outcome (40% improvement in disease activity according to the Assessment of SpondyloArthritis international Society criteria [ASAS40]) was compared in patients who received TNFα blockers versus control patients who received any other treatment (usual care). Controls were matched to the patients based on a propensity score method.

Results

A total of 30.2% (95% confidence interval [95% CI] 26.7–33.7) patients received at least 1 TNFα blocker during the 24 months of followup. The percentage of ASAS40 responders was 31.5% (62 of 197 patients) in the group receiving TNFα blockers versus 13.2% (26 of 197) in the control group (OR 2.99 [95% CI 1.80–4.99], P = 0.0002). This effectiveness was more pronounced in the subgroup of patients with sacroiliitis identified on magnetic resonance imaging, with 46% of ASAS40 responders receiving TNFα blockers versus 15% of ASAS40 responders receiving usual care (OR 4.99 [95% CI 2.17–11.51]).

Conclusion

Our study shows that TNFα blockers are frequently used in daily practice to treat patients with early axial SpA. Our findings confirm the effectiveness of TNFα blockers as compared to any other treatment, especially in the subgroup of patients with sacroiliitis on MRI.
Predictors of Treatment Resistance and Relapse in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: A Study of 439 Cases in a Single Chinese Center
Authors: Li Zhi‐Ying , Chang Dong‐Yuan , Zhao Ming‐Hui , Chen Min
Published: March 2014

Objective

Treatment resistance and relapse in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) are major challenges for physicians. The aim of this study was to assess the risk factors for treatment resistance and relapse in a single‐center cohort of Chinese patients with AAV.

Methods

Four hundred thirty‐nine consecutive patients with AAV were recruited for inclusion in this study. The value of various clinical and pathologic parameters for the prediction of treatment resistance and relapse was analyzed.

Results

Treatment resistance occurred in 47 (10.7%) of 439 patients and was independently associated with a higher serum creatinine level (odds ratio [OR] 1.087, 95% confidence interval [95% CI] 1.001–1.180, P = 0.047), a higher erythrocyte sedimentation rate (OR 1.009, 95% CI 1.001–1.018, P = 0.025), therapy with corticosteroids plus cyclophosphamide (OR 0.115, 95% CI 0.051–0.256, P = 0.000), and the presence of muscle pain (OR 0.249, 95% CI 0.083–0.747, P = 0.013). Relapse occurred in 128 (32.7%) of 392 patients in whom remission was achieved and was independently associated with lung involvement (hazard ratio [HR] 1.768, 95% CI 1.088–2.872, P = 0.021) and a lower serum creatinine level (HR 0.925, 95% CI 0.872–0.981, P = 0.009).

Conclusion

In Chinese patients with AAV, lung involvement and lower serum creatinine levels were independently associated with an increased risk of relapse. Elevated serum creatinine levels were associated with treatment resistance.
How much of the global information and communication explosion is driven by more, and how much by better technology?
Authors: Hilbert Martin
Published: March 2014

Technological change in the digital age is a combination of both more and better technology. This work quantifies how much of the technologically‐mediated information and communication explosion during the period of digitization (1986–2007) was driven by the deployment of additional technological devices, and how much by technological progress in hardware and software. We find that technological progress has contributed between two to six times more than additional technological infrastructure. While infrastructure seems to reach a certain level of saturation at roughly 20 storage devices per capita and 2 to 3 telecommunication subscriptions per capita, informational capacities are still expanding greatly. Besides progress in better hardware, software for information compression turns out to be an important and often neglected driver of the global growth of technologically‐mediated information and communication capacities.
Mendeley readership altmetrics for the social sciences and humanities: Research evaluation and knowledge flows
Authors: Mohammadi Ehsan , Thelwall Mike
Published: March 2014

Although there is evidence that counting the readers of an article in the social reference site, Mendeley, may help to capture its research impact, the extent to which this is true for different scientific fields is unknown. In this study, we compare Mendeley readership counts with citations for different social sciences and humanities disciplines. The overall correlation between Mendeley readership counts and citations for the social sciences was higher than for the humanities. Low and medium correlations between Mendeley bookmarks and citation counts in all the investigated disciplines suggest that these measures reflect different aspects of research impact. Mendeley data were also used to discover patterns of information flow between scientific fields. Comparing information flows based on Mendeley bookmarking data and cross‐disciplinary citation analysis for the disciplines revealed substantial similarities and some differences. Thus, the evidence from this study suggests that Mendeley readership data could be used to help capture knowledge transfer across scientific disciplines, especially for people that read but do not author articles, as well as giving impact evidence at an earlier stage than is possible with citation counts.
Managing the data commons: Controlled sharing of scholarly data
Authors: Eschenfelder Kristin R. , Johnson Andrew
Published: March 2014

This paper describes the range and variation in access and use control policies and tools used by 24 web‐based data repositories across a variety of fields. It also describes the rationale provided by repositories for their decisions to control data or provide means for depositors to do so. Using a purposive exploratory sample, we employed content analysis of repository website documentation, a web survey of repository managers, and selected follow‐up interviews to generate data. Our results describe the range and variation in access and use control policies and tools employed, identifying both commonalities and distinctions across repositories. Using concepts from commons theory as a guiding theoretical framework, our analysis describes the following five dimensions of repository rules, or data commons boundaries: locus of decision making (depositor vs. repository), degree of variation in terms of use within the repository, the mission of the repository in relation to its scholarly field, what use means in relation to specific sorts of data, and types of exclusion.
Hollow‐Shell‐Structured Nanospheres: A Recoverable Heterogeneous Catalyst for Rhodium‐Catalyzed Tandem Reduction/Lactonization of Ethyl 2‐Acylarylcarboxylates to Chiral Phthalides
Authors: Liu Rui , Jin Ronghua , An Juzeng , Zhao Qiankun , Cheng Tanyu , Liu Guohua
Published: March 2014

Chiral organorhodium‐functionalized hollow‐shell‐structured nanospheres were prepared by immobilization of a chiral N‐sulfonylated diamine‐based organorhodium complex within an ethylene‐bridged organosilicate shell. Structural analysis and characterization reveal its well‐defined single‐site rhodium active center, and transmission electron microscopy images reveal a uniform dispersion of hollow‐shell‐structured nanospheres. As a heterogenous catalyst, it exhibits excellent catalytic activity and enantioselectivity in synthesis of chiral phthalides by a tandem reduction/lactonization of ethyl 2‐acylarylcarboxylates in aqueous medium. The high catalytic performance is attributed to the synergistic effect of the high hydrophobicity and the confined chiral organorhodium catalytic nature. The organorhodium‐functionalized nanospheres could be conveniently recovered and reused at least 10 times without loss of catalytic activity. This feature makes it an attractive catalyst in environmentally friendly organic reactions. The results of this study offer a new approach to immobilize chiral organometal functionalities within the hollow‐shell‐structured nanospheres to prepare materials with high activity in heterogeneous asymmetric catalysis.
Supramolecular Hydrogels Made of Basic Biological Building Blocks
Authors: Du Xuewen , Zhou Jie , Xu Bing
Published: March 2014

As a consequence of the self‐assembly of small organic molecules in water, supramolecular hydrogels are evolving from serendipitous events during organic synthesis to become a new type of materials that hold promise for applications in biomedicine. In this Focus Review, we describe recent advances in the use of basic biological building blocks for creating molecules that act as hydrogelators and the potential applications of the corresponding hydrogels. After introducing the concept of supramolecular hydrogels and defining the scope of this review, we briefly describe the methods for making and characterizing supramolecular hydrogels. We then discuss representative hydrogelators according to the categories of their building blocks, such as amino acids, nucleobases, and saccharides, and highlight the applications of the hydrogels when necessary. Finally, we offer our perspective and outlook on this fast‐growing field at the interface of organic chemistry, materials, biology, and medicine. By providing a snapshot for chemists, engineers, and medical scientists, we hope that this Focus Review will contribute to the development of multidisciplinary research on supramolecular hydrogels for a wide range of applications in different fields.
Vascular mediators in chronic lung disease of infancy: Role of endothelial monocyte activating polypeptide II (EMAP II)
Authors: Lal Charitharth Vivek , Schwarz Margaret A.
Published: March 2014

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Over the years, the BPD phenotype has evolved, but despite various advances in neonatal management approaches, the reduction in the BPD burden is minimal. With the advent of surfactant, glucocorticoids, and new ventilation strategies, BPD has evolved from a disease of structural injury into a new BPD, marked by an arrest in alveolar growth in the lungs of extremely premature infants. This deficient alveolar growth has been associated with a diminution of pulmonary vasculature. Several investigators have described the epithelial / vascular co‐dependency and the significant role of crosstalk between vessel formation, alveologenesis, and lung dysplasia's; hence identification and study of factors that regulate pulmonary vascular emergence and inflammation has become crucial in devising effective therapeutic approaches for this debilitating condition. The potent antiangiogenic and proinflammatory protein Endothelial Monocyte Activating Polypeptide II (EMAP II) has been described as a mediator of pulmonary vascular and alveolar formation and its expression is inversely related to the periods of vascularization and alveolarization in the developing lung. Hence the study of EMAP II could play a vital role in studying and devising appropriate therapeutics for diseases of aberrant lung development, such as BPD. Herein, we review the vascular contribution to lung development and the implications that vascular mediators such as EMAP II have in distal lung formation during the vulnerable stage of alveolar genesis. Birth Defects Research (Part A) 100:180–188, 2014. © 2014 Wiley Periodicals, Inc.
Development of sensitive spectrofluorimetric and spectrophotometric methods for the determination of duloxetine in capsule and spiked human plasma
Authors: Sagirli Olcay , Toker Sıdıka Erturk , Önal Armağan
Published: March 2014

A new, sensitive and selective spectrofluorimetric method has been developed for the determination of duloxetine (DLX) in capsule and spiked human plasma. DLX, as a secondary amine compound, reacts with 7‐chloro‐4‐nitrobenzofurazon (NBD‐Cl), a highly sensitive fluorogenic and chromogenic reagent used in many investigations. The method is based on the reaction between the drug and NBD‐Cl in borate buffer at pH 8.5 to yield a highly fluorescent derivative that is measured at 523 nm after excitation at 478 nm. The fluorescence intensity was directly proportional to the concentration over the range 50–250 ng/mL. The reaction product was also measured spectrophotometrically. The relation between the absorbance at 478 nm and the concentration is rectilinear over the range 1.0–12.0 µg/mL. The methods were successfully applied for the determination of this drug in pharmaceutical dosage form. The spectrofluorimetric method was also successfully applied to the determination of duloxetine in spiked human plasma. The suggested procedures could be used for the determination of DLX in pure form, capsules and human plasma being sensitive, simple and selective. Copyright © 2014 John Wiley & Sons, Ltd.
Interplay between phase separation and gel formation in stirred acid milk/guar gum gels: Effect of acidification rate
Authors: Rohart Anne , Moulin Gabrielle , Michon Camille
Published: March 2014

The possibility of designing various microstructures through the interplay between phase separation due to depletion mechanisms and acid‐induced protein gelation was investigated. To modify the phase separation and gelation kinetics, guar gum/acid milk mixtures were acidified using glucono‐δ‐lactone at temperatures varying from 30 to 60°C. The microstructures of the stirred mixed gels were then discussed in light of the knowledge of the phase separation and gelation timescales. Small spherical protein‐enriched micro‐gels dispersed in a guar gum‐enriched continuous phase were found at high acidification temperatures, suggesting that the protein acid gelation kinetics was quicker than an extensive droplet growth through phase separation. For lower acidification temperatures, a region where droplet coalescence and sedimentation competed with gel formation was identified. Thus, depending on the residence time in that temperature domain, the resulting microstructures varied from spherical to extended filaments of more than 100 μm length. The results demonstrated that a broad range of defined microstructures can been created by triggered arrest through gelation of the phase‐separating structure. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 966–974, 2014.
Transcatheter neoaortic valve replacement utilizing the melody valve in hypoplastic left heart syndrome
Authors: Martin Mary Hunt , Gruber Peter J. , Gray Robert G.
Published: March 2014

Percutaneous transcatheter pulmonary valve replacement with the Melody Valve is fast becoming an important adjunct in the treatment of older children and adults with failing right ventricular outflow tract conduits. Recently, the Melody Valve has also been successfully implanted in the tricuspid, mitral, and aortic positions, typically within a failing bioprosthetic valve. We present a patient who underwent Fontan palliation for hypoplastic left heart syndrome variant and subsequently developed severe neoaortic regurgitation, which was successfully treated with a transcatheter neoaortic valve replacement. To our knowledge, this is the first successful use of the Melody Valve in the neoaortic position in a patient with single‐ventricle physiology. Successful relief of neoaortic valve regurgitation using replacement with a transcatheter valve may allow avoidance of additional surgery, increase functional longevity of single‐ventricle palliation, and postpone the need for orthotopic heart transplantation. © 2014 Wiley Periodicals, Inc.
Effect of CO2 on the DeNOx Activity of a Small Pore Zeolite Copper Catalyst for NH3/SCR
Authors: Kim Young Jin , Min Kyung Myung , Lee Jun Kyu , Hong Suk Bong , Cho Byong K. , Nam In‐Sik
Published: March 2014

Exposure of CuSSZ13 to CO2 at temperatures below 300 °C can deactivate its low‐temperature deNOx activity during NH3/SCR, with the severity of deactivation being dependent on reaction temperature. The adsorption of NO on Cu2+ ion is inhibited by CO2 due to its competitive adsorption, while NH3 adsorption on acidic sites of CuSSZ13 is largely unaffected by CO2, as evidenced by NO‐ and NH3‐TPD in the presence of CO2. Under O2‐rich conditions, CO2 forms unidentate carbonates on Cu2+ sites suppressing the formation of nitrates, a key reaction intermediate essential for NOx reduction during the NH3/SCR reaction, as revealed in an in situ FTIR study.
Selective Transfer Hydrogenation and Hydrogenation of Ketones Using a Defined Monofunctional (P^N(Bn)^N(Bn)^P)–RuII Complex
Authors: Hsu Shih‐Fan , Plietker Bernd
Published: March 2014

A defined (P^N^N^P)–Ru complex possessing tertiary amines within the ligand backbone proved to be highly active both in transfer hydrogenations and hydrogenations of a variety of ketones. As compared to the existing catalytic systems, no bifunctional activation of H2 or of the substrate by the metal center and a secondary amine within the ligand backbone is required to obtain high activities at catalyst loadings of down to 10 ppm.
Thermotropic Properties and Molecular Packing of Discotic Tristriazolotriazines with Rigid Substituents
Authors: Rieth Thorsten , Marszalek Tomasz , Pisula Wojciech , Detert Heiner
Published: March 2014

Tristriazolotriazines with a threefold dialkoxyaryl substitution have been prepared by Huisgen reaction of cyanuric chloride and the corresponding tetrazoles. Although these dyes show a negative or inverted solvatochromism of the UV/Vis absorption, their fluorescence is strongly positive solvatochromic. These discotic fluorophores are also emissive in their solid state and in their broad liquid‐crystalline mesophase. The structural study indicates that the thermotropic properties and organization of these systems can be well tuned by the steric demand of the aryl groups. Depending on the substituents, the compounds showed either a pure crystalline phase or a highly complex helical superstructure with a characteristic liquid‐crystalline phase at elevated temperatures. Changing the steric demand of the attached aryls allowed controlling the discs arrangement within the columnar helix, which is of great importance for the molecular orbital overlap.
Palladium/Norbornene‐Mediated Tandem CH Amination/CI Alkenylation Reaction of Aryl Iodides with Secondary Cyclic O‐Benzoyl Hydroxylamines and Activated Terminal Olefins
Authors: Chen Zhi‐Yuan , Ye Chang‐Qing , Zhu Hui , Zeng Xing‐Ping , Yuan Jian‐Jun
Published: March 2014

A novel palladium‐catalyzed norbornene‐mediated three‐component reaction for the construction of ortho‐alkenyl aromatic tertiary amines has been achieved, which represents a useful extension of the Catellani‐type tandem ortho‐selective CH amination transformations.
One‐Pot Protection‐Glycosylation Reactions for Synthesis of Lipid II Analogues
Authors: Mitachi Katsuhiko , Mohan Priya , Siricilla Shajila , Kurosu Michio
Published: March 2014

(2,6‐Dichloro‐4‐methoxyphenyl)(2,4‐dichlorophenyl)methyl trichloroacetimidate (3) and its polymer‐supported reagent 4 can be successfully applied to a one‐pot protection‐glycosylation reaction to form the disaccharide derivative 7 d for the synthesis of lipid II analogues. The temporary protecting group or linker at the C‐6 position and N‐Troc protecting group of 7 d can be cleaved simultaneously through a reductive condition. Overall yields of syntheses of lipid II (1) and neryl‐lipid II Nε‐dansylthiourea are significantly improved by using the described methods.
Reaction Monitoring Using Mid‐Infrared Laser‐Based Vibrational Circular Dichroism
Authors: Rüther Anja , Pfeifer Marcel , Lórenz‐Fonfría Víctor A. , Lüdeke Steffen
Published: March 2014

Changes in vibrational circular dichroism (VCD) were recorded on‐line during a chemical reaction. The chiral complex nickel‐(–)‐sparteine chloride was hydrolyzed to free (–)‐sparteine base in a biphasic system of sodium hydroxide solution and chloroform (CHCl3). Infrared (IR) and VCD spectra were iteratively recorded after pumping a sample from the CHCl3 phase through a lab‐built VCD spectrometer equipped with a tunable mid‐IR quantum cascade laser light source, which allows for VCD measurements even in the presence of strongly absorbing backgrounds. Time‐dependent VCD spectra were analyzed by singular value decomposition and global exponential fitting. Spectral features corresponding to the complex and free (–)‐sparteine could be clearly identified in the fitted amplitude spectrum, which was associated with an exponential decay with an apparent time constant of 127 min (t½ = 88 min). Chirality 26:490–496, 2014. © 2014 Wiley Periodicals, Inc.
Application of Regional Nutrient Management Model in Tunxi Catchment: In Support of the Trans‐boundary Eco‐compensation in Eastern China
Authors: Li Zeli , Liu Maohui , Zhao Yue , Liang Tao , Sha Jian , Wang Yuqiu
Published: March 2014

The first trans‐provincial watershed eco‐compensation pilot project has been implemented in Xin'anjiang River watershed, standing between China's Anhui Province and Zhejiang Province. The project purpose is to solve the trans‐boundary pollution issue, while ensuring sustainable use of water resources. Models have been proved to be effective tools for identifying major environmental objectives, especially in regard to the watershed management of agricultural non‐point source pollution. The regional nutrient management (ReNuMa) model was employed to interpret the main environmental problem (nitrogen contamination) generated within Tunxi catchment, the headstream of Xin'anjiang River watershed. After collecting and processing the available data and parameters, ReNuMa simulated stream flow, sediment yields and dissolved nitrogen loads on a monthly scale from 2000 to 2010 and thus estimated total nitrogen loads. Sensitivity and scenarios analysis were done to infer effective management options. The results showed that source apportionments of N loads emphasized the contribution proportion of each pollution source and characterized the temporal variations caused by natural and anthropogenic factors. Effective countermeasures were elicited by a series of scenarios analysis for water quality improvement. The application of the ReNuMa model showed usefulness to plan N management strategy for policy makers, which in turn helped reduce the N loads draining to the downstream, and gained mutual benefits from the ongoing trans‐provincial watershed eco‐compensation pilot project.
Distinct functions for IFT140 and IFT20 in opsin transport
Authors: Crouse Jacquelin A. , Lopes Vanda S. , SanAgustin Jovenal T. , Keady Brian T. , Williams David S. , Pazour Gregory J.
Published: March 2014

In the vertebrate retina, light is detected by the outer segments of photoreceptor rods and cones, which are highly modified cilia. Like other cilia, outer segments have no protein synthetic capacity and depend on proteins made in the cell body for their formation and maintenance. The mechanism of transport into the outer segment is not fully understood but intraflagellar transport (IFT) is thought to be a major mechanism for moving protein from the cell body into the cilium. In the case of photoreceptor cells, the high density of receptors and the disk turnover that occurs daily necessitates much higher rates of transport than would be required in other cilia. In this work, we show that the IFT complex A protein IFT140 is required for development and maintenance of outer segments. In earlier work we found that acute deletion of Ift20 caused opsin to accumulate at the Golgi complex. In this work, we find that acute deletion of Ift140 does not cause opsin to accumulate at the Golgi complex but rather it accumulates in the plasma membrane of the inner segments. This work is a strong support of a model of opsin transport where IFT20 is involved in the movement from the Golgi complex to the base of the cilium. Then, once at the base, the opsin is carried through the connecting cilium by an IFT complex that includes IFT140. © 2014 Wiley Periodicals, Inc.
Synthesis and Electron‐Transfer Processes in a New Family of Ligands for Coupled Ru−Mn2 Complexes
Authors: Karlsson Erik A. , Lee Bao‐Lin , Liao Rong‐Zhen , Åkermark Torbjörn , Kärkäs Markus D. , Becerril Valeria Saavedra , Siegbahn Per E. M. , Zou Xiaodong , Abrahamsson Maria , Åkermark Björn
Published: March 2014

A series of [Ru(bpy)3]2+‐type (bpy=2,2′‐bipyridine) photosensitisers have been coupled to a ligand for Mn, which is expected to give a dinuclear complex that is active as a water oxidation catalyst. Unexpectedly, photophysical studies showed that the assemblies had very short lived excited states and that the decay patterns were complex and strongly dependent on pH. One dyad was prepared that was capable of catalysing chemical water oxidation by using [Ru(bpy)3]3+ as an oxidant. However, photochemical water oxidation in the presence of an external electron acceptor failed, presumably because the short excited‐state lifetime precluded initial electron transfer to the added acceptor. The photophysical behaviour could be explained by the presence of an intricate excited‐state manifold, as also suggested by time‐dependent DFT calculations.
Host–Guest Nanocomposites of Multiwalled Carbon Nanotubes and Ionic Liquids with Controllable Composition
Authors: Ding Yuxiao , Su Dang Sheng
Published: March 2014

It is widely believed that low‐volatility is a defining characteristic of ionic liquids (ILs). Here we synthesize a series of host–guest nanocomposites containing multiwalled carbon nanotubes (MWCNTs) and ILs using the volatility of ILs under vacuum conditions. The nanocomposites with different IL contents can be easily obtained through simple physical methods. The interactions between IL and MWCNTs are thoroughly investigated. This new nanocomposite can be used both in carbon catalysis and IL catalysis.
Single‐Ion Polymer Electrolyte Membranes Enable Lithium‐Ion Batteries with a Broad Operating Temperature Range
Authors: Cai Weiwei , Zhang Yunfeng , Li Jing , Sun Yubao , Cheng Hansong
Published: March 2014

Conductive processes involving lithium ions are analyzed in detail from a mechanistic perspective, and demonstrate that single ion polymeric electrolyte (SIPE) membranes can be used in lithium‐ion batteries with a wide operating temperature range (25–80 °C) through systematic optimization of electrodes and electrode/electrolyte interfaces, in sharp contrast to other batteries equipped with SIPE membranes that display appreciable operability only at elevated temperatures (>60 °C). The performance is comparable to that of batteries using liquid electrolyte of inorganic salt, and the batteries exhibit excellent cycle life and rate performance. This significant widening of battery operation temperatures coupled with the inherent flexibility and robustness of the SIPE membranes makes it possible to develop thin and flexible Li‐ion batteries for a broad range of applications.
Detection of CFTR protein in human leukocytes by flow cytometry
Authors: Johansson Jan , Vezzalini Marzia , Verzè Genny , Caldrer Sara , Bolognin Silvia , Buffelli Mario , Bellisola Giuseppe , Tridello Gloria , Assael Baroukh Maurice , Melotti Paola , Sorio Claudio
Published: March 2014

Leukocytes have previously been shown to express detectable levels of the protein cystic fibrosis transmembrane conductance regulator (CFTR). This study aims to evaluate the application of flow cytometric (FC) analysis to detect CFTR expression, and changes thereof, in these cells. Aliquots (200 μL) of peripheral whole blood from 12 healthy control volunteers (CTRLs), 12 carriers of a CFTR mutation (CFC), and 40 patients with cystic fibrosis (CF) carrying various combinations of CFTR mutations were incubated with specific fluorescent probes recognizing CFTR protein expressed on the plasma membrane of leukocytes. FC was applied to analyze CFTR expression in monocytes, lymphocytes, and polymorphonuclear (PMN) cells. CFTR protein was detected in monocytes and lymphocytes, whereas inconclusive results were obtained from the analysis of PMN cells. Mean fluorescence intensity (MFI) ratio value and %CFTR‐positive cells above a selected threshold were the two parameters selected to quantify CFTR expression in cells. Lowest variability and the highest reproducibility were obtained when analyzing monocytes. ANOVA results indicated that both parameters were able to discriminate monocytes of healthy controls and CF individuals according to CFTR mutation classes with high accuracy. Significantly increased MFI ratio values were recorded in CFTR‐defective cells that were also able to improve CFTR function after ex vivo treatment with PTC124 (Ataluren), an investigative drug designed to permit the ribosome to read through nonsense CFTR mutations. The method described is minimally invasive and may be used in the monitoring of responses to drugs whose efficacy can depend on increased CFTR protein expression levels. © 2014 International Society for Advancement of Cytometry
Germ cell mutations of the ascidian Ciona intestinalis with TALE nucleases
Authors: Yoshida Keita , Treen Nicholas , Hozumi Akiko , Sakuma Tetsushi , Yamamoto Takashi , Sasakura Yasunori
Published: March 2014

Summary: Targeted mutagenesis of genes‐of‐interest, or gene‐knockout, is a powerful method to address the functions of genes. Engineered nucleases have enabled this approach in various organisms because of their ease of use. The ascidian Ciona intestinalis is an excellent organism to analyze gene functions by means of genetic technologies. In our previous study, we reported mutagenesis of Ciona somatic cells with TALE nucleases (TALENs) by electroporating expression constructs. In this study, we report germ cell mutagenesis of Ciona by microinjecting mRNAs encoding TALENs. TALEN mRNAs introduced mutations to target genes in both somatic and germ cells. TALEN‐mediated mutations in the germ cell genome were inherited by the next generation. We conclude that knockout lines of Ciona that have disrupted target genes can be established through TALEN‐mediated germ cell mutagenesis. genesis 52:431–439, 2014. © 2014 Wiley Periodicals, Inc.
Freeze drying for microencapsulation of α‐linolenic acid rich oil: A functional ingredient from Lepidium sativum seeds
Authors: Naik Azza , Meda V. , Lele S. S.
Published: March 2014

Lipids rich in polyunsaturated fatty acids (PUFA) are of great importance to the food industry. However, due to unsaturation they are highly prone to rancidity, thereby presenting an enormous technological challenge. Emulsification and subsequent microencapsulation of oil forms a protective micro‐environment for these bioactives. Further, freeze drying of emulsified lipids is used to enhance shelf‐life of the dietary targets. In the current study, α‐linolenic acid (ALA) rich oil from Lepidium sativum seed was stabilized through microencapsulation by freeze drying. O/W emulsion was prepared using a combination of gum ghatti, gum arabic, and soy protein isolate. Thereafter induced coacervates were lyophilized by the batch method in a tray dryer. The encapsulation procedure was optimized by the central composite design, through variation of parameters such as the ratio between gum and soy protein isolate (SPI), wall and core and the speed of homogenization. The response was measured in terms of microencapsulation efficiency (MEE) with the maxima of 81.11% for the parameter values of Gum:SPI at 0.32, Wall:Core at 2 and homogenization speed of 10 000 rpm. The prepared emulsion was characterized through ζ‐potential, viscosity, and droplet size measurements while the encapsulated product was deliberated through Raman spectroscopy and aw evaluations.

Practical applications: Dietary requirement of polyunsaturated fatty acids (PUFA) is seldom met by a vegetarian diet and therefore for the benefit of the vegetarian population, novel food products incorporating vegetarian PUFA need to be developed. However, rancidity is a major problem encountered while working on unsaturated molecules. Thus to gain maximum benefit from these functional lipids one needs to design stable bioavailable ingredients. With this in mind, the focus of the current study was formulation and process optimization to obtain encapsulated oil. Freeze drying process for microencapsulation leads to superior quality capsules due to the low temperature conditions. In this way L. sativum seed oil was explored for the first time to develop α‐linolenic acid rich bioactive ingredient.

Microencapsulation of PUFA rich oil by freeze drying. In the current study α‐linolenic acid rich oil was extracted from Lepidium sativum and processed into a functional ingredient by freeze drying. Soxhlet extracted oil along with SPI, gum arabic, and gum ghatti was utilized for formation of coacervates. Encapsulated oil in the form of coacervates was then dehydrated to form microcapsules in a freeze dryer. The capsules were then analyzed for microencapsulation efficiency and capsule composition. The optimized capsules can be used to deliver α‐linolenic acid rich oil in novel targeted food products.
Heavy metals in seawater, sediments, and biota from the coastal area of Yancheng City, China
Authors: Fu Jie , Wang Hui , Billah Shah M. Reduwan , Yu Hongxia , Zhang Xiaowei
Published: March 2014

A systematic investigation was carried out to analyze the concentration levels of heavy metals in sample seawater, sediments, and biota collected from the coastal area of Yancheng City in Jiangsu Province, China. The authors assessed the impact of these heavy metals in different environmental samples in terms of potential risks to ecology and also to the human population exposed to this area. In addition, a further investigation was carried out to test the toxicity to early-life-stage zebrafish (Danio rerio) of selected samples that were considered to pose higher levels of potential risks to ecology or human health. Chemical analysis showed relatively higher concentrations of heavy metals in the seawater and biota samples collected from Xiangshui County and Binhai County, China. The heavy metal concentrations in different samples collected from the close vicinity of Dafeng Port, China, were also considerable. In all seawater and sediment samples, heavy metals showed a relatively moderate level of risk to ecological species; for consumption of marine organisms, heavy metals had adverse impacts on human health. Toxicity assessment indicated that the selected environmental samples or their extracts had significant toxicity to zebrafish early-life stages, including lethality, teratogenicity, and hatching delay (or advance). Thus the present study provides highly useful and important information on heavy metal pollution in Jiangsu Province. Environ Toxicol Chem 2014;33:1697–1704. © 2014 SETAC
Clarifying relationships between persistent organic pollutant concentrations and age in wildlife biomonitoring: individuals, cross-sections, and the roles of lifespan and sex
Authors: Binnington Matthew J. , Wania Frank
Published: March 2014

Relationships between persistent organic pollutant (POP) levels and age in wildlife biomonitoring are often interpreted as changes in contaminant burden as organisms age. However, cross-sectional body burden-age trends (CBATs) obtained from biomonitoring studies, which sample individuals of different ages at the same time, should not be confused with longitudinal body burden-age trends (LBATs) obtained by sampling the same individuals repeatedly through time. To clarify how CBATs and LBATs for wildlife species deviate from each other, and describe any impact of lifespan and sex, we used mechanistic bioaccumulation models to estimate historic longitudinal exposures of polar cod, ringed seals, beluga whales, and bowhead whales to polychlorinated biphenyl congener 153. Cross-sectional body burden-age trends were then produced by sampling resultant LBATs of successive birth cohorts at specific time points. As found previously for humans, the year of sampling relative to the year of peak environmental contamination was a critical parameter in determining male CBAT shapes. However, a similar cohort effect was not apparent for reproductive females because efficient POP loss through lactation prevented their lipids from retaining a memory of past exposure levels. Thus, lactation loss was not only responsible for the large differences between the CBATs of males and females of the same species, but also the lack of female CBAT variability through time. Cross-sectional body burden-age trend shapes varied little between species by lifespan, as long as equivalent age scales were used. However, lifespan relative to the timescale of environmental contaminant level changes did determine the extent to which CBATs resembled LBATs for males. We suggest that accounting for birth cohort and sex effects is essential when interpreting age trends in POP biomonitoring studies of long-lived species. Environ Toxicol Chem 2014;33:1415–1426. © 2014 SETAC
Linalool: a review on a key odorant molecule with valuable biological properties
Authors: Aprotosoaie Ana Clara , Hăncianu Monica , Costache Irina‐Iuliana , Miron Anca
Published: March 2014

This paper reports on the occurrence, biosynthesis, metabolism, biological and toxicological profile, and assessment of the authenticity of linalool. The main biological properties of linalool – sedative, anxiolytic, analgesic, anticonvulsant, anti‐inflammatory, local anaesthetic – are discussed in terms of the molecule's chirality influence, the mechanisms of activity and type of study (in vitro, in vivo, clinical studies). Also, there is a discussion of the recent data on the skin sensitizing potential of linalool based on numerous scientific studies which have been performed in the last few years. Comments of the authenticity assessment of linalool are made considering the limitations imposed by the chemical structure, vegetal matrix or processing methods, but also from the perspective of the powerful and sophisticated analytical techniques available today (GC‐C‐IRMS, enantio‐MDGC coupled to GC‐C‐IRMS, SNIF‐NMR). Copyright © 2014 John Wiley & Sons, Ltd.
Futures Market Volatility: What Has Changed?
Authors: Bollen Nicolas P.B. , Whaley Robert E.
Published: March 2014

The evolution of trading practices in futures markets, including growth of high‐frequency trading, has raised concerns about market quality. This study investigates whether excess futures return volatility, as an encompassing gauge of market quality, has changed over time. Daily measures of realized volatility are computed using 5‐minute returns of 15 electronically traded futures contracts. Two benchmarks are used to control for changes in the rate of information flow: option implied volatility and long horizon volatility estimates. Relative to the benchmarks, realized volatility has not changed, indicating that changes in trading practices have not led to a deterioration of market quality. © 2014 Wiley Periodicals, Inc. Jrl Fut Mark 35:426–454, 2015
Visualization of the amygdalo–hippocampal border and its structural variability by 7T and 3T magnetic resonance imaging
Authors: Derix Johanna , Yang Shan , Lüsebrink Falk , Fiederer Lukas Dominique Josef , Schulze‐Bonhage Andreas , Aertsen Ad , Speck Oliver , Ball Tonio
Published: March 2014

The amygdala and the hippocampus are two adjacent structures in the medial temporal lobe that have been broadly investigated in functional and structural neuroimaging due to their central importance in sensory perception, emotion, and memory. Exact demarcation of the amygdalo‐hippocampal border (AHB) is, however, difficult in conventional structural imaging. Recent evidence suggests that, due to this difficulty, functional activation sites with high probability of being located in the hippocampus may erroneously be assigned to the amygdala, and vice versa. In the present study, we investigated the potential of ultra‐high‐field magnetic resonance imaging (MRI) in single sessions for detecting the AHB in humans. We show for the first time the detailed structure of the AHB as it can be visualized in T1‐weighted 7T in vivo images at 0.5‐mm3 isotropic resolution. Compared to data acquired at 3T, 7T images revealed considerably more structural detail in the AHB region. Thus, we observed a striking inter‐hemispheric and interindividual variability of the exact anatomical configuration of the AHB that points to the necessity of individual imaging of the AHB as a prerequisite for accurate anatomical assignment in this region. The findings of the present study demonstrate the usefulness of ultra‐high‐field structural MRI to resolve anatomical ambiguities of the human AHB. Highly accurate morphometric and functional investigations in this region at 7T may allow addressing such hitherto unexplored issues as whether the structural configuration of the AHB is related to functional differences in amygdalo‐hippocampal interaction. Hum Brain Mapp 35:4316–4329, 2014. © 2014 Wiley Periodicals, Inc.
Potential advantages of volumetric arc therapy in head and neck cancer
Authors: Gomez–Millan Barrachina Jaime , Jerez Sainz Inmaculada , Perez Rozos Alberto , Ramirez Ros J. Carlos , Toledo Serrano M. Dolores , Lupiañez Perez Yolanda , Medina Carmona J. Antonio
Published: March 2014

Background

Intensity‐modulated radiation therapy (IMRT) uses solid compensators or multileaf collimators to modulate the intensity of radiation in each field, delivering highly conformal dose distributions. This technique allows treating volumes with concave shapes when the target is close to a critical structure. The movement of multileaf collimator under computer control can modulate the dose in 3 main ways: IMRT with static field with segments, IMRT with dynamic delivery, and IMRT rotational therapy. Volumetric modulated arc therapy (VMAT) is a novel radiation technique that creates conformal distributions with variable gantry speed, dynamic movements of multileaf collimator, and variations in dose rate. The purpose of this study was to review the basis of VMAT, highlighting the differences with other IMRT techniques. © 2014 Wiley Periodicals, Inc. Head Neck 37: 909–914, 2015
Probing Superoxide Dismutases through Radiation Chemistry
Authors: Cabelli Diane
Published: March 2014

Superoxide dismutases (SODs) are metalloenzymes that likely evolved to remove superoxide (O2.−) from cells. These enzymes span a range of three uniquely different protein structures and four different metals to enable a similar overall chemistry, the catalytic and accelerated conversion of superoxide to oxygen and hydrogen peroxide. Superoxide dismutases have the attractive feature that the substrate (O2.−) for the catalytic reaction is easily generated using radiation chemistry, allowing the ability to follow catalysis on a fast time scale under a wide variety of conditions. This review will show how the utility of radiation chemistry was realized and enabled mechanistic understanding immediately upon discovery of these enzymes. It will then highlight some applications of pulse radiolysis, carried out in this laboratory, that illustrate mechanistic details of the enzyme function for a variety of wild‐type and mutant superoxide dismutases.
Population pharmacokinetics of the 5‐hydroxymethyl metabolite of tolterodine after administration of fesoterodine sustained release tablet in western and east Asian populations
Authors: Oishi Masayo , Tomono Yoshiro , Yamagami Hidetomi , Malhotra Bimal
Published: March 2014

This analysis was conducted to investigate factors that affect 5‐hydroxymethyl tolterodine (5‐HMT) pharmacokinetics after administration of fesoterodine sustained release tablets to Westerners and East Asians. Ten pharmacokinetic studies and three efficacy/safety studies in overactive bladder (OAB) patients were pooled for the population pharmacokinetic analysis. The plasma 5‐HMT concentration data were described by a 1‐compartment model with first order absorption and a lag time. Creatinine clearance (CLCR), hepatic impairment, CYP2D6 genotype, and concomitant medication with CYP3A inhibitor/inducer were identified as influential covariates. It was estimated that decreasing of CLCR from 80 to 15 mL/min resulted in a 39.5% reduction in 5‐HMT apparent oral clearance (CL/F). Hepatic impairment, CYP2D6 poor metabolizer, and CYP3A inhibitor were estimated to reduce CL/F by about 60%, 40%, and 50%, respectively. CYP3A inducer resulted in about fourfold increase in CL/F. Although sex and Japanese ethnicity were selected as covariates on CL/F, each resulted in only about 10% decrease and increase of CL/F, respectively. Of the influential covariates of 5‐HMT CL/F, CLCR, hepatic impairment, CYP2D6 genotype, and concomitant medication with CYP3A inhibitor/inducer were of significance, whereas sex and Japanese ethnicity covariates were considered not to have clinically significant impact on exposures of 5‐HMT.
Pharmacokinetic and pharmacodynamic drug–drug interaction assessment between pradigastat and digoxin or warfarin
Authors: Yan Jing‐He , Meyers Dan , Lee Zachary , Danis Kate , Neelakantham Srikanth , Majumdar Tapan , Rebello Sam , Sunkara Gangadhar , Chen Jin
Published: March 2014

Pradigastat, a novel diacylglycerol acyltransferase‐1 inhibitor, was evaluated for both pharmacokinetic (PK) and pharmacodynamic (PD) drug–drug interactions when co‐administered with digoxin or warfarin in healthy subjects. This open‐label study included two parallel subject cohorts each with three sequential treatment periods. Forty subjects were enrolled in the study with 20 subjects allocated to each cohort. PK and PD (PT/INR for warfarin only) samples were collected in each period. The statistical analysis results showed that the 90% CIs of the geometric mean ratios of digoxin, R‐warfarin, and S‐warfarin PK parameters (AUC and Cmax) were all within 0.80–1.25 interval. The 90% CIs of the geometric mean ratios of pradigastat PK parameters (AUC and Cmax) were within 0.80–1.25 interval when co‐administered with warfarin; while co‐administration with digoxin slightly reduced pradigastat exposure (∼15%). The results also showed that 90% CIs of the geometric mean ratios of warfarin PD parameters (AUCPT, PTmax, AUCINR, and INRmax) were within 0.80–1.25 interval. Pradigastat and digoxin or warfarin had no relevant clinical PK or PD drug–drug interactions. Administration of pradigastat and warfarin or pradigastat and digoxin as a mono or combined treatment appears to be safe and tolerated.