bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploitation of cold‐active cephalosporin C acylase by computer‐aided directed evolution and its potential application in low‐temperature biosynthesis of 7‐aminocephalosporanic acid
Authors: Tang Cun‐Duo , Shi Hong‐Ling , Jiao Zhu‐Jin , Shi Hong‐Fei , Yao Lun‐Guang , Xu Jian‐He , Kan Yun‐Chao 
Published: March 2018

AbstractBACKGROUNDCephalosporin C acylase (CA) plays a key role in the one‐step enzymatic catalysis of 7‐aminocephalosporanic acid (7‐ACA) from Cephalosporin C (CPC). However, the synthesis of 7‐ACA needs low‐temperature conditions: unless catalyzed at 13 °C, it will produce large amounts of undesired products. Unfortunately, cephalosporin CA catalyzes CPC to 7‐ACA directly at a very low efficiency at 13 °C or below.RESULTSIn this work, multiple techniques including molecular docking, multi‐site random‐directed mutagenesis and high‐throughput screening were adopted and combined into an engineering strategy to improve the cold adaptability of CA. Thus, the best‐hit mutant 9H9 containing mutations of P238G, P449G and P582G was screened revealing a specific activity of 1.94 U mg−1 at 13 °C, which is 1.3‐fold higher than that of the parent. Compared with the parent, the mutant 9H9 shows a slight decline in the Km value and significant improvement in the Vmax value. In addition, the yield of 7‐ACA catalyzed by 9H9 was obviously higher than that of the parent at low temperature.CONCLUSIONA new and viable strategy was established for improving the cold adaptability of CA and investigations were made into enhancing its conformational flexibility. This might lay a solid foundation for future study and industrial application of CAs. © 2018 Society of Chemical Industry
Development of Mimokines, chemokine N terminus-based CXCR4 inhibitors optimized by phage display and rational design
Authors: Fievez Virginie , Szpakowska Martyna , Mosbah Amor , Arumugam Karthik , Mathu Julie , Counson Manuel , Beaupain Nadia , Seguin-Devaux Carole , Deroo Sabrina , Baudy-Floc’h Michèle , Chevigné Andy 
Published: March 2018

Abstract
The chemokine receptor CXCR4 (C-X-C chemokine receptor type 4 also known as fusin or CD184 (cluster of differentiation 184)) is implicated in various biological and pathological processes of the hematopoietic and immune systems. CXCR4 is also one of the major coreceptors for HIV-1 entry into target cells and is overexpressed in many cancers, supporting cell survival, proliferation, and migration. CXCR4 is thus an extremely relevant drug target. Among the different strategies to block CXCR4, chemokine-derived peptide inhibitors hold great therapeutic potential. In this study, we used the N-terminus of vCCL2/vMIPII, a viral CXCR4 antagonist chemokine, as a scaffold motif to engineer and select CXCR4 peptide inhibitors, called Mimokines, which imitate the chemokine-binding mode but display an enhanced receptor affinity, antiviral properties, and receptor selectivity. We first engineered a Mimokine phage displayed library based on the first 21 residues of vCCL2, in which cysteine 11 and 12 were fully randomized and screened it against purified CXCR4 stabilized in liposomes. We identified Mimokines displaying up to 4-fold higher affinity for CXCR4 when compared to the reference peptide and fully protected MT-4 cells against HIV-1 infection. These selected Mimokines were then subjected to dimerization, D-amino acid, and aza-β3-amino acid substitution to further enhance their potency and selectivity. Optimized Mimokines exhibited up to 120-fold enhanced CXCR4 binding (range of 20 nM) and more than 200-fold improved antiviral properties (≤ 1 μM) compared to the parental Mimokines. Interestingly, these optimized Mimokines also showed up to 25-fold weaker affinity for ACKR3/CXCR7 and may therefore serve as lead compounds for further development of more selective CXCR4 peptide inhibitors and probes.
Development of CXCR4 peptide inhibitors with enhanced receptor affinity/selectivity and antiviral properties.
Repeatability, reproducibility, and accuracy of quantitative mri of the breast in the community radiology setting
Authors: Sorace Anna G. , Wu Chengyue , Barnes Stephanie L. , Jarrett Angela M. , Avery Sarah , Patt Debra , Goodgame Boone , Luci Jeffery J. , Kang Hakmook , Abramson Richard G. , Yankeelov Thomas E. , Virostko John 
Published: March 2018

BackgroundQuantitative diffusion‐weighted MRI (DW‐MRI) and dynamic contrast‐enhanced MRI (DCE‐MRI) have the potential to impact patient care by providing noninvasive biological information in breast cancer.Purpose/HypothesisTo quantify the repeatability, reproducibility, and accuracy of apparent diffusion coefficient (ADC) and T1‐mapping of the breast in community radiology practices.Study TypeProspective.Subjects/PhantomIce‐water DW‐MRI and T1 gel phantoms were used to assess accuracy. Normal subjects (n = 3) and phantoms across three sites (one academic, two community) were used to assess reproducibility. Test–retest analysis at one site in normal subjects (n = 12) was used to assess repeatability.Field Strength/Sequence3T Siemens Skyra MRI quantitative DW‐MRI and T1‐mapping.AssessmentQuantitative DW‐MRI and T1‐mapping parametric maps of phantoms and fibroglandular and adipose tissue of the breast.Statistical TestsAverage values of breast tissue were quantified and Bland–Altman analysis was performed to assess the repeatability of the MRI techniques, while the Friedman test assessed reproducibility.ResultsADC measurements were reproducible across sites, with an average difference of 1.6% in an ice‐water phantom and 7.0% in breast fibroglandular tissue. T1 measurements in gel phantoms had an average difference of 2.8% across three sites, whereas breast fibroglandular and adipose tissue had 8.4% and 7.5% average differences, respectively. In the repeatability study, we found no bias between first and second scanning sessions (P = 0.1). The difference between repeated measurements was independent of the mean for each MRI metric (P = 0.156, P = 0.862, P = 0.197 for ADC, T1 of fibroglandular tissue, and T1 of adipose tissue, respectively).Data ConclusionCommunity radiology practices can perform repeatable, reproducible, and accurate quantitative T1‐mapping and DW‐MRI. This has the potential to dramatically expand the number of sites that can participate in multisite clinical trials and increase clinical translation of quantitative MRI techniques for cancer response assessment.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;48:695–707.
Dynamic effects of personal initiative on engagement and exhaustion: The role of mood, autonomy, and support
Authors: Zacher Hannes , Schmitt Antje , Jimmieson Nerina L. , Rudolph Cort W. 
Published: March 2018

SummaryResearchers have neglected dynamic effects of proactive behavior on occupational well‐being. We investigated effects of change in personal initiative over 6 months on changes in emotional engagement and exhaustion over the following 6 months. On the basis of the control‐process theory on affect, we hypothesized that changes in positive and negative moods mediate these effects conditional upon employees' level of perceived organizational support. On the basis of action regulation theory, we assumed that change in job autonomy also acts as a mediator. Data came from 297 employees who responded to 3 surveys separated by 6‐month intervals. Results of latent change score modeling showed that change in personal initiative negatively predicted change in positive mood and, when perceived organizational support was low, positively predicted change in negative mood. In addition, change in personal initiative positively predicted change in job autonomy. Change in personal initiative had negative indirect effects on change in emotional engagement, and positive indirect effects on change in emotional exhaustion through changes in positive and negative moods (but not through change in job autonomy). A reverse causal model did not yield significant indirect effects. Overall, these findings suggest that an increase in proactive behavior can have detrimental effects on occupational well‐being.
An intercomparison of a large ensemble of statistical downscaling methods over Europe: Results from the VALUE perfect predictor cross‐validation experiment
Authors: Gutiérrez J. M. , Maraun D. , Widmann M. , Huth R. , Hertig E. , Benestad R. , Roessler O. , Wibig J. , Wilcke R. , Kotlarski S. , San Martín D. , Herrera S. , Bedia J. , Casanueva A. , Manzanas R. , Iturbide M. , Vrac M. , Dubrovsky M. , Ribalaygua J. , Pórtoles J. , Räty O. , Räisänen J. , Hingray B. , Raynaud D. , Casado M. J. , Ramos P. , Zerenner T. , Turco M. , Bosshard T. , Štěpánek P. , Bartholy J. , Pongracz R. , Keller D. E. , Fischer A. M. , Cardoso R. M. , Soares P. M. M. , Czernecki B. , Pagé C. 
Published: March 2018

VALUE is an open European collaboration to intercompare downscaling approaches for climate change research, focusing on different validation aspects (marginal, temporal, extremes, spatial, process‐based, etc.). Here we describe the participating methods and first results from the first experiment, using “perfect” reanalysis (and reanalysis‐driven regional climate model (RCM)) predictors to assess the intrinsic performance of the methods for downscaling precipitation and temperatures over a set of 86 stations representative of the main climatic regions in Europe. This study constitutes the largest and most comprehensive to date intercomparison of statistical downscaling methods, covering the three common downscaling approaches (perfect prognosis, model output statistics—including bias correction—and weather generators) with a total of over 50 downscaling methods representative of the most common techniques.Overall, most of the downscaling methods greatly improve (reanalysis or RCM) raw model biases and no approach or technique seems to be superior in general, because there is a large method‐to‐method variability. The main factors most influencing the results are the seasonal calibration of the methods (e.g., using a moving window) and their stochastic nature. The particular predictors used also play an important role in cases where the comparison was possible, both for the validation results and for the strength of the predictor–predictand link, indicating the local variability explained. However, the present study cannot give a conclusive assessment of the skill of the methods to simulate regional future climates, and further experiments will be soon performed in the framework of the EURO‐CORDEX initiative (where VALUE activities have merged and follow on).Finally, research transparency and reproducibility has been a major concern and substantive steps have been taken. In particular, the necessary data to run the experiments are provided at http://www.value‐cost.eu/data and data and validation results are available from the VALUE validation portal for further investigation: http://www.value‐cost.eu/validationportal.
Homogeneous and Heterogeneous Catalyzed Esterification of Acrylic Acid with Ethanol: Reaction Kinetics and Modeling
Authors: Jyoti Ghoshna , Keshav Amit , Anandkumar J. , Bhoi Stutee 
Published: March 2018

ABSTRACTKinetics of esterification of acrylic acid with ethanol in the presence of homogeneous (H2SO4, HCl, p‐TSA, HI) catalysts as well as heterogeneous catalysts (Dowex 50WX, Amberlyst 15) was studied. The effects and performance of these catalysts on the conversion of acrylic acid were evaluated. In the kinetics of homogeneous catalyzed reaction, both concentration and activity‐based model were employed. Activity coefficients were predicted by the Universal Functional group Contribution (UNIFAC) method to consider nonideal behavior of the liquid phase. The heterogeneous catalyzed reaction mechanisms were developed using Eley–Rideal theory. The model results were compared with the experimental results and were in good agreement. The temperature dependency of the constants, reaction enthalpy, and entropy, and activation energy were determined. The conversion of acrylic acid was obtained as 63.2%, 61.02%, 53.3%, 21.4%, 34.96%, and 14.84% for H2SO4, p‐TSA, HCl, HI, Dowex 50WX, and Amberlyst 15, respectively, under process temperature of 70°C, reactant molar ratio of 1:1, and catalyst concentration of 2% (v/v) for homogeneous and 2.17 g for heterogeneous catalyst. These outcomes provide an approach to understand the significant effect of each catalyst on the esterification kinetics of acrylic acid and ethanol.
Revise the ICMJE Recommendations regarding authorship responsibility!
Authors: Helgesson Gert , Eriksson Stefan 
Published: March 2018

Key points
A clear set of rules regarding authorship responsibilities in academic publications is much needed.
The leading research integrity guidelines on scientific authorship, the International Committee of Medical Journal Editors Recommendations, are unclear about authorship responsibilities in case of misconduct.
The source of the problem is the fourth authorship criterion – it should be revised.
Dietary High‐Oleic Acid Soybean Oil Dose Dependently Attenuates Egg Yolk Content of n‐3 Polyunsaturated Fatty Acids in Laying Hens Fed Supplemental Flaxseed Oil
Authors: Elkin Robert G. , Kukorowski Alexandra N. , Ying Yun , Harvatine Kevin J. 
Published: March 2018

AbstractChickens can hepatically synthesize eicosapentaenoic acid (20:5 n‐3) and docosahexaenoic acid (22:6 n‐3) from α‐linolenic acid (ALA; 18:3 n‐3); however, the process is inefficient and competitively inhibited by dietary linoleic acid (LNA; 18:2 n‐6). In the present study, the influence of dietary high‐oleic acid (OLA; 18:1 n‐9) soybean oil (HOSO) on egg and tissue deposition of ALA and n‐3 polyunsaturated fatty acids (PUFA) synthesized from dietary ALA was investigated in laying hens fed a reduced‐LNA base diet supplemented with high‐ALA flaxseed oil (FLAX). We hypothesized that reducing the dietary level of LNA would promote greater hepatic conversion of ALA to very long‐chain (VLC; >20C) n‐3 PUFA, while supplemental dietary HOSO would simultaneously further enrich eggs with OLA without influencing egg n‐3 PUFA contents. Nine 51‐week‐old hens each were fed 0, 10, 20, or 40 g HOSO/kg diet for 12 weeks. Within each group, supplemental dietary FLAX was increased every 3 weeks from 0 to 10 to 20 to 40 g/kg diet. Compared to controls, dietary FLAX maximally enriched the total n‐3 and VLC n‐3 PUFA contents in egg yolk by 9.4‐fold and 2.2‐fold, respectively, while feeding hens 40 g HOSO/kg diet maximally attenuated the yolk deposition of ALA, VLC n‐3 PUFA, and total n‐3 PUFA by 37, 15, and 32%, respectively. These results suggest that dietary OLA is not neutral with regard to the overall process by which dietary ALA is absorbed, metabolized, and deposited into egg yolk, either intact or in the form of longer‐chain/more unsaturated n‐3 PUFA derivatives.
Multiple solutions for a noncooperative Kirchhoff‐type system involving the fractional p‐Laplacian and critical exponents
Authors: Liang Sihua , Molica Bisci Giovanni , Zhang Binlin 
Published: March 2018

AbstractIn this paper, we use the Limit Index Theory due to Li and the fractional version of concentration compactness principle to study the multiplicity of solutions for a class of noncooperative fractional p‐Laplacian elliptic system with homogeneous Dirichlet boundary conditions involving the critical exponents.
A remark on the number field analogue of Waring's constant
Authors: Pollack Paul 
Published: March 2018

AbstractLet K be a number field, and let k be an integer with . Let be the collection of totally nonnegative integers in K (i.e., the totally positive integers together with zero). We let denote the smallest positive integer with the following property: Every element of that is a sum of kth powers of elements of is the sum of g such kth powers. Work of Siegel in the 1940s shows that is well‐defined for all k and K. In this note, we prove that cannot be bounded by a function of k alone: For each , .
Quality of Life in Huntington's Disease: Critique and Recommendations for Measures Assessing Patient Health‐Related Quality of Life and Caregiver Quality of Life
Authors: Mestre Tiago A. , Carlozzi Noelle E. , Ho Aileen K. , Burgunder Jean‐Marc , Walker Francis , Davis Aileen M. , Busse Monica , Quinn Lori , Rodrigues Filipe B. , Sampaio Cristina , Goetz Christopher G. , Cubo Esther , Martinez‐Martin Pablo , Stebbins Glenn T. ,   Members of the MDS Committee on Rating Scales Development
Published: March 2018

ABSTRACTThe compromise of quality of life in Huntington's disease is a major issue, both for individuals with the disease as well as for their caregivers. The International Parkinson and Movement Disorder Society commissioned a review of the use and clinimetric validation status of measures used in Huntington's disease to assess aspects related with quality of life and to make recommendations on their use following standardized criteria. We included both patient‐centered measures (patient health‐related quality‐of‐life measures) and caregiver‐centered measures (caregiver quality‐of‐life measures). After conducting a systematic literature search, we included 12 measures of patient health‐related quality of life and 2 measures of caregiver quality of life. Regarding patient‐centered measures, the Medical Outcomes Study 36‐Item Short‐Form Health Survey is “recommended” as a generic assessment of health‐related quality of life in patients with Huntington's disease. The 12‐Item Short Form Health Survey, the Sickness Impact Profile, the 12‐item World Health Organization Disability Assessment Schedule, and the Huntington's Disease Health‐Related Quality of Life questionnaire are “suggested.” No caregiver‐centered quality‐of‐life measure obtained a “recommended” status. The Alzheimer's Carer's Quality of Life Inventory and the Huntington's Disease Quality of Life Battery for Carers are “suggested.” Recognizing that the assessment of patient health‐related quality of life can be challenging in Huntington's disease, as patients may lack insight and there is insufficient clinimetric testing of these scales, the committee concluded that further validation of currently available health‐related quality‐of‐life measures should be undertaken, namely, those Huntington's disease–specific health‐related quality‐of‐life measures that have recently been reported and used. © 2018 International Parkinson and Movement Disorder Society
International Parkinson and movement disorder society evidence‐based medicine review: Update on treatments for the motor symptoms of Parkinson's disease
Authors: Fox Susan H. , Katzenschlager Regina , Lim Shen‐Yang , Barton Brandon , de Bie Rob M. A. , Seppi Klaus , Coelho Miguel , Sampaio Cristina ,   on behalf of the Movement Disorder Society Evidence‐Based Medicine Committee
Published: March 2018

ABSTRACTObjective: The objective of this review was to update evidence‐based medicine recommendations for treating motor symptoms of Parkinson's disease (PD).Background: The Movement Disorder Society Evidence‐Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016.Methods: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported.Results: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise‐based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful.Conclusions: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society
Impact of joint statistical dual‐energy CT reconstruction of proton stopping power images: Comparison to image‐ and sinogram‐domain material decomposition approaches
Authors: Zhang Shuangyue , Han Dong , Politte David G. , Williamson Jeffrey F. , O'Sullivan Joseph A. 
Published: March 2018

PurposeThe purpose of this study was to assess the performance of a novel dual‐energy CT (DECT) approach for proton stopping power ratio (SPR) mapping that integrates image reconstruction and material characterization using a joint statistical image reconstruction (JSIR) method based on a linear basis vector model (BVM). A systematic comparison between the JSIR‐BVM method and previously described DECT image‐ and sinogram‐domain decomposition approaches is also carried out on synthetic data.MethodsThe JSIR‐BVM method was implemented to estimate the electron densities and mean excitation energies (I‐values) required by the Bethe equation for SPR mapping. In addition, image‐ and sinogram‐domain DECT methods based on three available SPR models including BVM were implemented for comparison. The intrinsic SPR modeling accuracy of the three models was first validated. Synthetic DECT transmission sinograms of two 330 mm diameter phantoms each containing 17 soft and bony tissues (for a total of 34) of known composition were then generated with spectra of 90 and 140 kVp. The estimation accuracy of the reconstructed SPR images were evaluated for the seven investigated methods. The impact of phantom size and insert location on SPR estimation accuracy was also investigated.ResultsAll three selected DECT‐SPR models predict the SPR of all tissue types with less than 0.2% RMS errors under idealized conditions with no reconstruction uncertainties. When applied to synthetic sinograms, the JSIR‐BVM method achieves the best performance with mean and RMS‐average errors of less than 0.05% and 0.3%, respectively, for all noise levels, while the image‐ and sinogram‐domain decomposition methods show increasing mean and RMS‐average errors with increasing noise level. The JSIR‐BVM method also reduces statistical SPR variation by sixfold compared to other methods. A 25% phantom diameter change causes up to 4% SPR differences for the image‐domain decomposition approach, while the JSIR‐BVM method and sinogram‐domain decomposition methods are insensitive to size change.ConclusionAmong all the investigated methods, the JSIR‐BVM method achieves the best performance for SPR estimation in our simulation phantom study. This novel method is robust with respect to sinogram noise and residual beam‐hardening effects, yielding SPR estimation errors comparable to intrinsic BVM modeling error. In contrast, the achievable SPR estimation accuracy of the image‐ and sinogram‐domain decomposition methods is dominated by the CT image intensity uncertainties introduced by the reconstruction and decomposition processes.