bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Integrated Radiographic Data From Two Long‐Term, Open‐Label Extension Studies of Adalimumab for the Treatment of Rheumatoid Arthritis
Authors: Landewé Robert , Østergaard Mikkel , Keystone Edward C. , Florentinus Stefan , Liu Shufang , van der Heijde Désirée 
Published: July 2014

ObjectiveA longitudinal integration approach evaluated all radiographic scores assessed over 10 years, rather than only completer data, from 2 studies of adalimumab (ADA) for rheumatoid arthritis (RA).MethodsThe DE019 (methotrexate [MTX]–inadequate responders, longstanding RA) and PREMIER (MTX‐naive, early RA) studies, respectively, had 1‐ or 2‐year double‐blind periods followed by 9‐ or 8‐year open‐label extensions (OLEs). Patients received ADA ± MTX in both OLEs. Radiographic progression was assessed using change from baseline in modified total Sharp score (ΔmTSS). A mixed‐effects model was used post hoc to evaluate repeated measurements of different data campaigns and to estimate ΔmTSS through up to 10 years of treatment based on original randomization groups (placebo [PBO] + MTX or standard dose ADA + MTX).ResultsData from patients with baseline and ≥1 postbaseline radiograph were included (n = 327 for DE019; n = 452 for PREMIER). Integrated and 10‐year completer ΔmTSS progression curves differed slightly. In DE019, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 6.6 units (integrated model) and 6.2 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 0.9 units by integrated analysis and 0.7 units in completers. In PREMIER, for patients originally assigned PBO + MTX, accrued ΔmTSS at year 10 was 11.2 units (integrated analysis) and 11.0 units (completers). For patients originally assigned ADA + MTX, accrued ΔmTSS was 5.1 units (integrated analysis) and 4.0 units (completers). A higher radiographic progression rate was observed in patients who received delayed versus immediate ADA + MTX treatment.ConclusionsLongitudinal integrated analysis provided robust estimates of radiographic progression that only slightly differed from completers‐only scores and confirmed the effects.
Preparation of the First Manganese(III) and Manganese(IV) Azides
Authors: Haiges Ralf , Buszek Robert J. , Boatz Jerry A. , Christe Karl O. 
Published: July 2014

AbstractFluoride‐azide exchange reactions of Me3SiN3 with MnF2 and MnF3 in acetonitrile resulted in the isolation of Mn(N3)2 and Mn(N3)3⋅CH3CN, respectively. While Mn(N3)2 forms [PPh4]2[Mn(N3)4] and (bipy)2Mn(N3)2 upon reaction with PPh4N3 and 2,2′‐bipyridine (bipy), respectively, the manganese(III) azide undergoes disproportionation and forms mixtures of [PPh4]2[Mn(N3)4] and [PPh4]2[Mn(N3)6], as well as (bipy)2Mn(N3)2 and (bipy)Mn(N3)4. Neat and highly sensitive Cs2[Mn(N3)6] was obtained through the reaction of Cs2MnF6 with Me3SiN3 in CH3CN.
Determination of a novel phosphodiesterase4 inhibitor, 3‐[1‐(3cyclopropylmethoxy‐4‐difluoromethoxybenzyl)‐1H‐pyrazol‐3‐yl]‐benzoic acid (PDE‐423) in rat plasma using liquid chromatography–tandem mass spectrometry
Authors: Cho Woon‐Ki , Seo Hyewon , Choi Sung Heum , Kwak Hyun Jeong , Cheon Hyae Gyeong , Jeon Dong Ju , Kim Sang Kyum , Bae Myung Ae , Song Jin Sook 
Published: July 2014

AbstractA method for determining a novel phosphodiesterase‐4 inhibitor, 3‐[1‐(3cyclopropylmethoxy‐4‐difluoromethoxybenzyl)‐1H‐pyrazol‐3‐yl]‐benzoic acid (PDE‐423), in rat plasma was developed and validated using liquid chromatography–tandem mass spectrometry for further pharmacokinetic study for development as a novel anti‐asthmatic drug. PDE‐423 in the concentration range of 0.02–10 µg/mL was linear with a correlation coefficient of >0.99, and the mean intra‐ and inter‐assay precisions of the assay were 7.50 and 3.86%, respectively. The validated method was used successfully for a pharmacokinetic study of PDE‐423 in rats. Copyright © 2014 John Wiley & Sons, Ltd.
Development of a liquid chromatography–mass spectrometry method for determination of agrimol B in rat plasma: application to preclinical pharmacokinetics
Authors: Wang Zhenglin , Liu Peng , Liang Pin , Hu Xiang 
Published: July 2014

AbstractA sensitive and accurate liquid chromatography coupled with mass spectrometry (LC‐MS) method was developed for the determination of agrimol B, a main active ingredient isolated from Agrimonia pilosa Ledeb., in rat plasma. Chromatographic separation was achieved on a Zorbax CN column (150 × 4.6 mm, 5 µm), with isocratic elution consisting of acetonitrile and water (15:85, v/v) at a flow rate of 0.6 mL/min. Agrimol B and dryocrassin ABBA, an internal standard (IS), were analyzed by selected ion monitoring at m/z transitions of 681.3 and 819.4, respectively. This assay exhibited a good linearity with a correlation coefficient >0.99 and showed no endogenous interference with the analyte and IS. The limit of quantification of agrimol B was 8.025 ng/mL with acceptable precision and accuracy. The method was successfully applied in the pharmacokinetic study of agrimol B in rats after intravenous (1 mg/kg) and oral (2, 5 and 10 mg/kg) doses of agrimol B. The absolute bioavailability of agrimol B was 16.4–18.0% in rat. Our study clarifies the pharmacokinetic behavior of agrimol B in animals. Copyright © 2014 John Wiley & Sons, Ltd.
Maltodextrins as Chiral Selectors in CE: Molecular Structure Effect of Basic Chiral Compounds on the Enantioseparation
Authors: Tabani Hadi , Fakhari Ali Reza , Nojavan Saeed 
Published: July 2014

ABSTRACTPrediction of chiral separation for a compound using a chiral selector is an interesting and debatable work. For this purpose, in this study 23 chiral basic drugs with different chemical structures were selected as model solutes and the influence of their chemical structures on the enantioseparation in the presence of maltodextrin (MD) as chiral selector was investigated. For chiral separation, a 100‐mM phosphate buffer solution (pH 3.0) containing 10% (w/v) MD with dextrose equivalent (DE) of 4‐7 as chiral selector at the temperature of 25°C and voltage of 20 kV was used. Under this condition, baseline separation was achieved for nine chiral compounds and partial separation was obtained for another six chiral compounds while no enantioseparation was obtained for the remaining eight compounds. The results showed that the existence of at least two aromatic rings or cycloalkanes and an oxygen or nitrogen atom or –CN group directly bonded to the chiral center are necessary for baseline separation. With the obtained results in this study, chiral separation of a chiral compound can be estimated with MD‐modified capillary electrophoresis before analysis. This prediction will minimize the number of preliminary experiments required to resolve enantiomers and will save time and cost. Chirality 26:620–628, 2014. © 2014 Wiley Periodicals, Inc.
Committed Tc17 cells are phenotypically and functionally resistant to the effects of IL‐27
Authors: El‐Behi Mohamed , Dai Hong , Magalhaes Joao G. , Hwang Daniel , Zhang Guang‐Xian , Rostami Abdolmohamad , Ciric Bogoljub 
Published: July 2014

IL‐17‐secreting CD8+ T cells (Tc17 cells) have been implicated in immunity to infections, cancer, and autoimmune diseases. Thus far, studies on Tc17 cells have primarily investigated their development from naïve precursors, while the biology of committed Tc17 cells has been less characterized, in particular during the effector phase of immune responses. IL‐27 is an important regulator of inflammation through the induction of regulatory Tr1 cells, as well as a suppressor of Th17‐cell development. IL‐27 suppresses the development of Tc17 cells, but its effects on committed Tc17 cells are unknown. Here we demonstrate that even though IL‐27 completely inhibited the development of C57BL/6 mouse Tc17 cells, it had little effect on previously committed Tc17 cells. Although committed Tc17 cells were capable of responding to IL‐27, it had no effect on expression of RORγt and RORα, or production of various cytokines. Committed Tc17 cells did not express granzyme B and lacked cytotoxicity in vitro, features that remained unaltered by IL‐27 treatment. Nonetheless, they efficiently induced diabetes, irrespective of treatment with IL‐27 prior to transfer into RIP‐mOVA mice. These findings suggest that use of IL‐27 to modulate autoimmune diseases might have limited therapeutic efficacy if autoaggressive Tc17 cells have already developed.
Investigating the effects of knowledge and ideology on climate change beliefs
Authors: Guy Sophie , Kashima Yoshihisa , Walker Iain , O'Neill Saffron 
Published: July 2014

AbstractThe divergence of public opinion and climate science in the English‐speaking world, particularly the United States and Australia, has attracted a variety of explanations. One of the more interesting accounts, from a psychological perspective, is the influence of ideology on climate change beliefs. Previous work suggests that ideology trumps knowledge in shaping climate change beliefs. However, these studies have typically examined the influence of proxy measures of knowledge rather than specific climate change knowledge. The goal of the present research was to provide some clarification on the different influences of knowledge and ideology on beliefs about climate change. Specifically, we investigated the relationship between specific climate change knowledge, hierarchical and individualistic ideology, and climate change belief in a national sample (N = 335) of the Australian public. Contrary to research involving proxy knowledge measures, we found that people who had greater knowledge of climate change causes were more willing to accept that climate change is occurring. Furthermore, knowledge of causes attenuated the negative relationship between individualistic ideology and belief that climate change exists. Our findings suggest that climate change knowledge has the potential to positively influence public discourse on the issue. Copyright © 2014 John Wiley & Sons, Ltd.
Would you rule out going green? The effect of inclusion versus exclusion mindset on pro‐environmental willingness
Authors: McDonald Rachel I. , Newell Ben R. , Denson Thomas F. 
Published: July 2014

AbstractTwo experiments demonstrate that participants' willingness to endorse adopting pro‐environmental behaviors is influenced substantially by a decision‐framing effect: the inclusion–exclusion discrepancy. Participants were presented with a list of 26 pro‐environmental behaviors (e.g., take a shorter shower, buy local produce). In both experiments, participants asked to cross out the behaviors they would not be willing to engage in (exclusion mindset) generated 30% larger consideration sets than those asked to circle behaviors that they would be willing to do (inclusion mindset). Experiment 2 identified qualities of the behaviors that accounted for the differences in the size of consideration sets, namely effort and opportunity. The results suggest the counter‐intuitive notion that encouraging people to think about what they would not do for the environment might lead them to do more. Copyright © 2014 John Wiley & Sons, Ltd.
Quantitative analysis of a ubiquitin‐dependent substrate using capillary electrophoresis with dual laser‐induced fluorescence
Authors: Lee Hyunjung , Ban Eunmi , Kim Eunice EunKyeong , Yoo Young Sook , Lee Daekee , Song Eun Joo 
Published: July 2014

Protein degradation by the ubiquitin‐proteasome system (UPS) affects many biological processes. Inhibition of the proteasome has emerged as a potential therapeutic target for cancer treatment. In this study, we developed a method for monitoring the degradation and accumulation of UPS‐dependent substrates in cells using CE with dual LIF. We used a green fluorescent protein (GFP)‐fusion of the ubiquitin substrate ribophorin 1 (GFP‐RPN1) along with red fluorescent protein (RFP) as an internal control to normalize transfection efficiency. Determination of GFP‐RPN1 and RFP in cell lysates were performed in an untreated capillary (75 μm × 50 cm) and 100 mM Tris‐CHES buffer (pH 9.0) containing 10 mM SDS. GFP‐RPN1 and RFP fluorescence were detected at excitation wavelengths of 488 and 635 nm, and emission wavelengths of 520 and 675 nm, respectively, without any interference or crosstalk. The intensity of GFP‐RPN1 fluorescence was normalized to that of RFP. Additionally, the proposed approach was used successfully to detect the degradation of GFP‐RPN1 and evaluate proteasome inhibitors. These results show that the developed method is effective and promising for rapid and quantitative monitoring of UPS‐dependent substrates compared to the current common methods, such as immunoblotting and pulse chase assays.
Nano-silicon dioxide mitigates the adverse effects of salt stress on Cucurbita pepo L
Authors: Siddiqui Manzer H. , Al-Whaibi Mohamed H. , Faisal Mohammad , Al Sahli Abdulaziz A. 
Published: July 2014

Abstract

Research into nanotechnology, an emerging science, has advanced in almost all fields of technology. The aim of the present study was to evaluate the role of nano-silicon dioxide (nano-SiO2) in plant resistance to salt stress through improvement of the antioxidant system of squash (Cucurbita pepo L. cv. white bush marrow). Seeds treated with NaCl showed reduced germination percentage, vigor, length, and fresh and dry weights of the roots and shoots. However, nano-SiO2 improved seed germination and growth characteristics by reducing malondialdehyde and hydrogen peroxide levels as well as electrolyte leakage. In addition, application of nano-SiO2 reduced chlorophyll degradation and enhanced the net photosynthetic rate (Pn), stomatal conductance (gs), transpiration rate, and water use efficiency. The increase in plant germination and growth characteristics through application of nano-SiO2 might reflect a reduction in oxidative damage as a result of the expression of antioxidant enzymes, such as catalase, peroxidase, superoxide dismutase, glutathione reductase, and ascorbate peroxidase. These results indicate that nano-SiO2 may improve defense mechanisms of plants against salt stress toxicity by augmenting the Pn, gs, transpiration rate, water use efficiency, total chlorophyll, proline, and carbonic anhydrase activity in the leaves of plants. Environ Toxicol Chem 2014;33:2429–2437. © 2014 SETAC
Optimized MEGA‐SPECIAL for in vivo glutamine detection in the rat brain at 14.1 T
Authors: Craveiro Mélanie , Cudalbu Cristina , Mlynárik Vladimir , Gruetter Rolf 
Published: July 2014

Glutamine has multiple roles in brain metabolism and its concentration can be altered in various pathological conditions. An accurate knowledge of its concentration is therefore highly desirable to monitor and study several brain disorders in vivo. However, in recent years, several MRS studies have reported conflicting glutamine concentrations in the human brain. A recent hypothesis for explaining these discrepancies is that a short T2 component of the glutamine signal may impact on its quantification at long echo times.The present study therefore aimed to investigate the impact of acquisition parameters on the quantified glutamine concentration using two different acquisition techniques, SPECIAL at ultra‐short echo time and MEGA‐SPECIAL at moderate echo time. For this purpose, MEGA‐SPECIAL was optimized for the first time for glutamine detection.Based on the very good agreement of the glutamine concentration obtained between the two measurements, it was concluded that no impact of a short T2 component of the glutamine signal was detected. Copyright © 2014 John Wiley & Sons, Ltd.
Expanding the structure–activity relationship of sulfoxaflor: the synthesis and biological activity of N‐heterocyclic sulfoximines
Authors: Nugent Benjamin M , Buysse Ann M , Loso Michael R , Babcock Jon M , Johnson Timothy C , Oliver M Paige , Martin Timothy P , Ober Matthias S , Breaux Nneka , Robinson Andrew , Adelfinskaya Yelena 
Published: July 2014

AbstractBACKGROUNDSulfoxaflor, a new insect control agent developed by Dow AgroSciences, exhibits broad‐spectrum control of many sap‐feeding insect pests, including aphids, whiteflies, leafhoppers, planthoppers and lygus bugs. During the development of sulfoxaflor, structure–activity relationship (SAR) exploration of the sulfoximine functional group revealed that the nature of the sulfoximine nitrogen substituent significantly affects insecticidal acitivity. As part of the investigation to probe the various electronic, steric and lipophilic parameters at this position, a series of N‐heterocyclic sulfoximines were synthesized and tested for bioactivity against green peach aphid.RESULTSUsing a variety of chemistries, the nitrile substituent was replaced with different substituted five‐ and six‐membered heterocycles. The compounds in the series were then tested for insecticidal acitivty against green peach aphid in foliar spray assays. In spite of the larger steric demand of these substituents, the resulting N‐heterocyclic sulfoximine analogs displayed good levels of efficacy. In particular, the N‐thiazolyl sulfoximines exhibited the greatest activity, with LC50 values as low as 1 ppm.CONCLUSIONSThe novel series of N‐heterocyclic sulfoximines helped to advance the current knowledge of the sulfoxaflor SAR, and demonstrated that the structural requirement for the sulfoximine nitrogen position was not limited to small, electron‐deficient moeities, but rather was tolerant of larger functionality. © 2014 Society of Chemical Industry
Scalable VANET content routing using hierarchical bloom filters
Authors: Yu Yu‐Ting , Gerla Mario , Sanadidi M. Y. 
Published: July 2014

AbstractIn this paper, we discuss scalable content‐oriented routing that enables storing, sharing, and searching data totally within the urban VANET. We introduce a scalable proactive content discovery scheme, hierarchical bloom‐filter routing (HBFR), to tackle mobility, large population, and rich content challenges of VANETs. Our simulation results show that HBFR achieves low latency and high content availability with relatively low overhead in practical VANET scenarios. In particular, HBFR improves the response time by up to 45% compared with the conventional Content Centric Networking (CCN) and reduces the traffic by up to 85% compared with timer‐based intelligent content search. HBFR suits the popular private data services the best and also achieves low response time comparable with that of flooding‐based content discovery when applying to popular public data services.Copyright © 2014 John Wiley & Sons, Ltd.
Enhanced production of Thermomyces lanuginosus lipase in Pichia pastoris via genetic and fermentation strategies
Authors: Fang Zhonggang , Xu Li , Pan Dujie , Jiao Liangcheng , Liu Ziming , Yan Yunjun 
Published: July 2014

Abstract
This study attempted to enhance the expression level of Thermomyces lanuginosus lipase (TLL) in Pichia pastoris using a series of strategies. The tll gene was first inserted into the expression vector pPIC9 K and transformed into P. pastoris strain GS115. The maximum hydrolytic activity of TLL reached 4,350 U/mL under the optimal culture conditions of a 500 mL shaking flask containing 20 mL culture medium with the addition of 1.2 % (w/v) methanol, cultivation for 144 h at pH 7.0 and 27 °C. To further increase the TLL expression and copy number, strains containing two plasmids were obtained by sequential electroporation into GS115/9k-TLL #3 with a second vector, either pGAPZαA-TLL, pFZα-TLL, or pPICZαA-TLL. The maximum activity of the resultant strains GS115/9KTLL-ZαATLL #40, GS115/9KTLL-FZαATLL #46 and GS115/9KTLL-GAPTLL #45 was 6,600 U/mL, 6,000 U/mL and 4,800 U/mL, respectively. The tll copy number in these strains, as assessed by real-time quantitative PCR, was demonstrated to be seven, five, and three, respectively, versus two copies in GS115/9k-TLL #3. When a co-feeding strategy of sorbitol/methanol was adopted in a 3-L fermenter, the maximum TLL activity of GS115/9k-TLL #3 increased to 27,000 U/mL after 130 h of fed-batch fermentation, whereas, the maximum TLL activity was 19,500 U/mL after 145 h incubation when methanol was used as the sole carbon source.
Genetic Information, Non‐Discrimination, and Privacy Protections in Genetic Counseling Practice
Authors: Prince Anya E. R. , Roche Myra I. 
Published: July 2014

AbstractThe passage of the Genetic Information Non Discrimination Act (GINA) was hailed as a pivotal achievement that was expected to calm the fears of both patients and research participants about the potential misuse of genetic information. However, 6 years later, patient and provider awareness of legal protections at both the federal and state level remains discouragingly low, thereby, limiting their potential effectiveness. The increasing demand for genetic testing will expand the number of individuals and families who could benefit from obtaining accurate information about the privacy and anti‐discriminatory protections that GINA and other laws extend. In this paper we describe legal protections that are applicable to individuals seeking genetic counseling, review the literature on patient and provider fears of genetic discrimination and examine their awareness and understandings of existing laws, and summarize how genetic counselors currently discuss genetic discrimination. We then present three genetic counseling cases to illustrate issues of genetic discrimination and provide relevant information on applicable legal protections. Genetic counselors have an unprecedented opportunity, as well as the professional responsibility, to disseminate accurate knowledge about existing legal protections to their patients. They can strengthen their effectiveness in this role by achieving a greater knowledge of current protections including being able to identify specific steps that can help protect genetic information.
Streamlining the Imaging of Clinically Suspected Pheochromocytoma: Using Urine Metanephrines to Decrease Imaging Costs
Authors: Stamm Michael , Abele Jonathan T. 
Published: July 2014

Purpose To improve the cost efficiency of the imaging evaluation of clinically suspected pheochromocytoma by using 24-hour fractionated urine metanephrine (FUM) results. Methods A retrospective review of I-123 meta-iodo-benzyl-guanidine single photon emission tomography (SPECT) computed tomography (CT) studies performed at our institution between January 2007 and February 2011 for clinically suspected pheochromocytoma was performed. SPECT-CT results from 70 patients were compared with results from 24-hour FUM analysis (within 2 months of SPECT-CT) and with relevant CT or magnetic resonance imaging studies (within 6 months of SPECT-CT). An imaging algorithm was developed to maximize cost efficiency without altering the final imaging interpretation. Actual imaging costs for the studied cohort were compared with the expected costs if this algorithm had been applied. Results If the 24-hour FUMs were normal, then all the SPECT-CT studies were negative (16/70). Eighty-seven percent of patients with abnormal total metanephrine had a positive SPECT-CT. If the total metanephrine was normal but 1 or more of the metanephrine fractions were abnormal, then 39%-58% of the SPECT-CT studies were positive. Within this subgroup, none had a positive SPECT-CT if a CT or magnetic resonance image was negative or benign. The actual imaging costs averaged CAD$2833.19 per patient for this cohort. Applying a streamlined imaging algorithm guided by 24-hour FUM analysis would result in an average imaging cost of CAD$1225.97 per patient without an expected change in the final imaging impression. Conclusion By using 24-hour FUM results to streamline imaging, considerable cost savings per patient (56.7%) can be attained without a change in the final overall imaging interpretation.