bluuebunny/crossref_metadata_2025_split huggingface dataset:
Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells
Authors: Wei Jun , Xia Siyuan , Sun Huayan , Zhang Song , Wang Jingya , Zhao Huiyuan , Wu Xiaoli , Chen Xi , Hao Jianlei , Zhou Xinglong , Zhu Zhengmao , Gao Xiang , Gao Jian-xin , Wang Puyue , Wu Zhenzhou , Zhao Liqing , Yin Zhinan 
Published: June 2013

Abstract
Critical roles of IL-27 in autoimmune diseases and infections have been reported; however, the contribution of endogenous IL-27 to tumor progression remains elusive. In this study, by using IL-27p28 conditional knockout mice, we demonstrate that IL-27 is critical in protective immune response against methyl-cholanthrene–induced fibrosarcoma and transplanted B16 melanoma, and dendritic cells (DCs) are the primary source. DC-derived IL-27 is required for shaping tumor microenvironment by inducing CXCL-10 expression in myeloid-derived suppressor cells and regulating IL-12 production from DCs, which lead to the recruitment and activation of NK and NKT cells resulting in immunological control of tumors. Indeed, reconstitution of IL-27 or CXCL-10 in tumor site significantly inhibits tumor growth and restores the number and activation of NK and NKT cells. In summary, our study identifies a previous unknown critical role of DC-derived IL-27 in NK and NKT cell–dependent antitumor immunity through shaping tumor microenvironment, and sheds light on developing novel therapeutic approaches based on IL-27.
Engineering a Blood-Retinal Barrier With Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium: Transcriptome and Functional Analysis
Authors: Peng Shaomin , Gan Geliang , Qiu Caihong , Zhong Mei , An Hongyan , Adelman Ron A. , Rizzolo Lawrence J. 
Published: June 2013

Abstract
Retinal degenerations are a major cause of impaired vision in the elderly. Degenerations originate in either photoreceptors or the retinal pigment epithelium (RPE). RPE forms the outer blood-retinal barrier and functions intimately with photoreceptors. Animal models and cultures of RPE are commonly used to screen potential pharmaceuticals or explore RPE replacement therapy, but human RPE differs from that of other species. Human RPE forms a barrier using tight junctions composed of a unique set of claudins, proteins that determine the permeability and selectivity of tight junctions. Human adult RPE fails to replicate these properties in vitro. To develop a culture model for drug development and tissue-engineering human retina, RPE were derived from human embryonic stem cells (hESCs). Barrier properties of RPE derived from the H1 and H9 hESC lines were compared with a well-regarded model of RPE function, human fetal RPE isolated from 16-week-gestation fetuses (hfRPE). A serum-free medium (SFM-1) that enhanced the redifferentiation of hfRPE in culture also furthered the maturation of hESC-derived RPE. In SFM-1, the composition, selectivity, and permeability of tight junctions were similar to those of hfRPE. Comparison of the transcriptomes by RNA sequencing and quantitative reverse transcription-polymerase chain reaction revealed a high correlation between the hESCs and hfRPE, but there were notable differences in the expression of adhesion junction and membrane transport genes. These data indicated that hESC-derived RPE is highly differentiated but may be less mature than RPE isolated from 16-week fetuses. The study identified a panel of genes to monitor the maturation of RPE.
Decision‐making Under Uncertainty in the Cash Cab
Authors: Kelley Matthew R. , Lemke Robert J. 
Published: June 2013

SummaryTelevision game shows have long been used to analyze risk‐taking behavior. We used episodes of Cash Cab to investigate how a variety of pre‐game and in‐game factors affected contestants' decisions to accept or reject a double‐or‐nothing gamble offered at the end of the game. As expected, the analysis confirmed the standard influences of gender, age, and group size on the willingness to accept the gamble. More interestingly, however, the data suggested that contestants also used in‐game experiences to update their subjective probability of success when considering the final gamble. Surprisingly, contestants did not appear to use correct performance (e.g., number correct, and streaks of correct) when updating, but the number and distribution of highly confident and correct responses were important when assessing the final gamble. Copyright © 2013 John Wiley & Sons, Ltd.
Tuning of Cell–Biomaterial Anchorage for Tissue Regeneration
Authors: Leal‐Egaña Aldo , Díaz‐Cuenca Aránzazu , Boccaccini Aldo R. 
Published: June 2013

AbstractWhich mechanisms mediate cell attachment to biomaterials? What role does the surface charge or wettability play on cell–material anchorage? What are the currently investigated strategies to modify cell–matrix adherence spatiotemporally? Considering the development of scaffolds made of biocompatible materials to temporarily replace the structure and/or function of the extracellular matrix, focus is given to the analysis of the specific (i.e., cell adhesive peptide sequences) and unspecific (i.e., surface charge, wettability) mechanisms mediating cell‐matrix interactions. Furthermore, because natural tissue regeneration is characterized by the dynamic attachment/detachment of different cell populations, the design of advanced scaffolds for tissue engineering, based in the spatiotemporal tuning of cell–matrix anchorage is discussed.
Nitrilase Activity Screening on Structurally Diverse Substrates: Providing Biocatalytic Tools for Organic Synthesis
Authors: Vergne‐Vaxelaire Carine , Bordier Franck , Fossey Aurélie , Besnard‐Gonnet Marielle , Debard Adrien , Mariage Aline , Pellouin Virginie , Perret Alain , Petit Jean‐Louis , Stam Mark , Salanoubat Marcel , Weissenbach Jean , De Berardinis Véronique , Zaparucha Anne 
Published: June 2013

AbstractA high‐throughput screening of candidate nitrilases against 25 structurally diverse substrates allowed us to create a wide collection of 125 experimentally validated nitrilases. The enzymes were selected by genomic approach from 700 diverse prokaryotic species and one metagenome as representative of the nitrilase family diversity. The enzymatic screening of this collection expands the biocatalytic toolbox for chemical synthesis by providing a large number of tested nitrilases with their assigned substrates. Three examples illustrate the synthetic potential of our enzyme collection. The syntheses of carboxylic acid building blocks, a β‐substituted phenylpropanoic acid, a cyclic γ‐keto carboxylic acid and a mononitrile monocarboxylic acid, were achieved from the corresponding nitrile substrates, using three new nitrilases (two from Sphingomonas wittichii and one from Syntrophobacter fumaroxidans). Improvements of nitrilase activities through the optimization of reaction parameters and the preparative biocatalytic synthesis are presented for these three examples.
An Efficient Tetrabutylammonium Fluoride (TBAF)‐Catalyzed Three‐Component Synthesis of 3‐Substituted Indole Derivatives under Solvent‐Free Conditions
Authors: Singh Neetu , Allam Bharat Kumar , Raghuvanshi Dushyant Singh , Singh Krishna Nand 
Published: June 2013

AbstractAn expedient and efficient one‐pot three‐component synthesis of 3‐substituted indoles has been developed by the reaction of indoles, active methylene compounds and aldehydes using a catalytic amount of tetrabutylammonium fluoride under solvent‐free conditions.
Direct Regio‐, Diastereo‐, and Enantioselective Vinylogous Michael Addition of Prochiral 3‐Alkylideneoxindoles to Nitroolefins
Authors: Rassu Gloria , Zambrano Vincenzo , Pinna Luigi , Curti Claudio , Battistini Lucia , Sartori Andrea , Pelosi Giorgio , Zanardi Franca , Casiraghi Giovanni 
Published: June 2013

Abstract3‐Alkylidene‐2‐oxindoles represent a simple, yet enabling subfamily of indole alkaloids, and their ability to react as electron‐poor acceptors has largely been investigated. In contrast, their utility as pronucleophilic synthons remains elusive. In this context, the present article describes the successful execution of the direct, organocatalytic asymmetric Michael addition of prochiral 3‐alkylideneoxindoles to nitroolefins. A variety of γ‐substituted alkylideneoxindoles carrying two stereocenters at both the γ‐ and δ‐carbon sites was assembled with excellent stereoselectivity and without olefin isomerization or stereochemical ablation.
Reserve site selection for data‐poor invertebrate fisheries using patch scale and dispersal dynamics: a case study of sea cucumber(Cucumaria frondosa)
Authors: Shackell Nancy L. , Brickman David W. , Frank Kenneth T. 
Published: June 2013

ABSTRACTGlobally, management decisions for recently established invertebrate fisheries are based on limited information. The negative consequences are being realized as now at least one‐third of invertebrate fisheries are over‐exploited, collapsed or closed. Management of a fishery should be based on abundance and productivity data. This information is often unavailable but in some jurisdictions, spatial distributions are known. A methodology for designating a network of reserves for sedentary invertebrates, using sea cucumber (Cucumaria frondosa) on the Scotian Shelf, Canada is proposed, as a case study.It is assumed that there is a positive relationship between spawner density and per capita population growth rate in sedentary broadcast spawners and that fertilization success declines rapidly at low densities. Protection of high‐density habitat would safeguard critical spawner density, especially when the critical density is unknown. Using spatial distribution, a method to identify size and location of reserves designed to protect high‐density habitat was developed.First, geographically distinct regional‐scale clusters are identified. Within clusters, the characteristic patch scale was determined through spatial autocorrelation analysis. The size of reserves can be set as 50% of each high‐density patch based on an appropriate risk‐averse approach.The allocation of reserve size and location is not dependent on results of a numerical circulation model. However, the analysis was refined by using one to predict larval drift patterns, and connectivity among patches. Reserve boxes were then designated to safeguard from 30 to 65% of each high‐density patch.Marine reserves do not work if inappropriately sited. In the absence of any other information, it is argued that siting reserves on high‐density areas is an essential and appropriate approach to data‐poor invertebrate fisheries management. A high percentage of each high‐density patch could serve as risk‐averse ‘spatial management’ reference points, and could be modified once replenishment rates are known.Copyright © Her Majesty the Queen in Right of Canada 2013
Inhibition of Lactoperoxidase‐Catalyzed Oxidation by Imidazole‐Based Thiones and Selones: A Mechanistic Study
Authors: Roy Gouriprasanna , Jayaram P. N. , Mugesh Govindasamy 
Published: June 2013

AbstractHerein, we describe the synthesis and biomimetic activity of a series of N,N‐disubstituted thiones and selones that contain an imidazole pharmacophore. The N,N‐disubstituted thiones do not show any inhibitory activity towards LPO‐catalyzed oxidation reactions, but their corresponding N,N‐disubstituted selones exhibit inhibitory activity towards LPO‐catalyzed oxidation reactions. Substituents on the N atom of the imidazole ring appear to have a significant effect on the inhibition of LPO‐catalyzed oxidation and iodination reactions. Selones 16, 17, and 19, which contain methyl, ethyl, and benzyl substituents, exhibit similar inhibition activities towards LPO‐catalyzed oxidation reactions with IC50 values of 24.4, 22.5, and 22.5 μM, respectively. However, their activities are almost three‐fold lower than that of the commonly used anti‐thyroid drug methimazole (MMI). In contrast, selone 21, which contains a NCH2CH2OH substituent, exhibits high inhibitory activity, with an IC50 value of 7.2 μM, which is similar to that of MMI. The inhibitory activity of these selones towards LPO‐catalyzed oxidation/iodination reactions is due to their ability to decrease the concentrations of the co‐substrates (H2O2 and I2), either by catalytically reducing H2O2 (anti‐oxidant activity) or by forming stable charge‐transfer complexes with oxidized iodide species. The inhibition of LPO‐catalyzed oxidation/iodination reactions by N,N‐disubstituted selones can be reversed by increasing the concentration of H2O2. Interestingly, all of the N,N‐disubstituted selones exhibit high anti‐oxidant activities and their glutathione peroxidase (GPx)‐like activity is 4–12‐fold higher than that of the well‐known GPx‐mimic ebselen. These experimental and theoretical studies suggest that the selones exist as zwitterions, in which the imidazole ring contains a positive charge and the selenium atom carries a large negative charge. Therefore, the selenium moieties of these selones possess highly nucleophilic character. The 77Se NMR chemical shifts for the selones show large upfield shift, thus confirming the zwitterionic structure in solution.
A novel solid‐phase extraction–spectrofluorimetric method for the direct determination of atenolol in human urine
Authors: Basan Hasan , Yarımkaya Sezen 
Published: June 2013

ABSTRACTA novel, simple, sensitive and selective solid‐phase extraction (SPE)–spectrofluorimetric method has been developed for the determination of atenolol (ATE) in human urine. Because an extraction procedure is required to isolate ATE or eliminate the interfering molecules present in complex human urine for the direct spectrofluorimetric determination, a pH‐sensitive poly(acrylic acid‐ethylene glycol dimethacrylate) [poly(AA‐EGDMA)] hydrogel was developed and used as a SPE adsorbent. Some factors affecting the ATE extraction efficiency, such as washing solvent type and volume, and the volume of elution solvent were optimized. Eluates from SPE cartridges were analyzed using a spectrofluorimeter (λex = 277 nm and λem = 300 nm). The calibration graph was linear over the concentration range 0.15–4.0 µg/mL. Limit of detection (LOD) and limit of quantification (LOQ) values were found to be 0.03 and 0.10 µg/mL, respectively. Relatively high intraday [2.06%, mean relative standard deviation (RSD)] and interday (2.6%, mean RSD) precisions were achieved. High mean recovery (95.4%) and low RSD values (3.8%) were obtained for spiked ATE in human urine. The spectrofluorimetric method presented here can be easily applied to assay trace amounts of ATE in pharmaceuticals and biological samples. Copyright © 2013 John Wiley & Sons, Ltd.
Fundamental interactions in RNA: Questions answered and remaining
Authors: Turner Douglas H. 
Published: June 2013

ABSTRACTInterpreting the tsunami of sequence information for RNA would be facilitated by an understanding of all the physical principles determining RNA structure. In principle, a complete understanding would make it computationally possible to find RNA sequences that fold for function and to predict their three‐dimensional structure. It would, thus, also facilitate discovery of new principles relating structure to function. This review covers some of the progress in understanding RNA over roughly the preceding 40 years and suggests progress still to be made. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1097–1104, 2013.
Semi‐rational engineering of cytochrome P450sca‐2 in a hybrid system for enhanced catalytic activity: Insights into the important role of electron transfer
Authors: Ba Lina , Li Pan , Zhang Hui , Duan Yan , Lin Zhanglin 
Published: June 2013

ABSTRACTHybrid P450 systems in which P450 monooxygenases are reconstituted with non‐native or surrogate redox partners have become important for the engineering of this class of versatile enzymes. P450sca‐2 fromStreptomyces carbophilusstereoselectively hydroxylates mevastatin to yield pravastatin, a cholesterol‐lowering drug. WhileS. carbophilushas been successfully applied in the industrial biotransformation process for pravastatin, the molecular study and engineering of P450sca‐2 has been very limited. We have previously established a functional P450sca‐2/Pdx/Pdr hybrid system. In this study, on the basis of a more active P450sca‐2 mutant (R8‐5C), five sites located in the substrate binding pocket, substrate access entrance, and presumed Pdx interaction interface were rationally chosen, and systematically subjected to site‐directed saturation mutagenesis (SDSM), and three rounds of iterative saturation mutagenesis (ISM). A best mutant (Variant III) was obtained, which showed a whole cell biotransformation activity (377.5 mg/L) and an overall apparentkcat(6.37 min−1) that was 7.1‐ and 10.0‐fold that of the starting template R8‐5C, respectively. Kinetic characterization revealed that most of the improvements seen for the SDSM and ISM mutants came from enhanced overall electron transfer, with the two sites at the interface between P450sca‐2 and Pdx (T119 and N363) being most critical. Our study underscores the important role of electron transfer in a hybrid P450 system, and also demonstrates the utility of ISM in optimizing the redox partner interface. This should facilitate engineering of this and other important hybrid P450 systems. Biotechnol. Bioeng. 2013;110: 2815–2825. © 2013 Wiley Periodicals, Inc.
Strain optimization for efficient isobutanol production using Corynebacterium glutamicum under oxygen deprivation
Authors: Yamamoto Shogo , Suda Masako , Niimi Satoko , Inui Masayuki , Yukawa Hideaki 
Published: June 2013

ABSTRACTMicrobial production of isobutanol is made difficult by the chemical's high cell toxicity. Corynebacterium glutamicum, inherently one of the more isobutanol‐tolerant industrial microorganisms, exhibits unprecedented productivity under oxygen deprivation, potentially allowing for high productivity of such toxic chemicals as isobutanol. Here, we show that development of C. glutamicum strains proficient in isobutanol production depends not only on modulating the activity of 2‐keto acid decarboxylase (KDC) and isobutanol dehydrogenase (IBDH) and suppressing by‐product formation, but also on optimizing the production process to eschew product inhibition. Isobutanol production under oxygen deprivation reached 343 mM (3.2% v/v) in strain IBU5 expressing kivd (encoding KDC) under the control of ldhA promoter and adhP (encoding IBDH from Escherichia coli MG1655) under the control of gapA promoter. This productivity is double the previously reported best productivity of 1.6% (v/v) and exceeds the 2.5% (v/v) limit beyond which cell growth becomes too severely suppressed. Irrespective, a cumulative 56.5% improvement on yield was possible with the combined effects of disruption of the ppc gene, encoding phosphoenolpyruvate carboxylase (PEPC), use of a NAD+‐specific mutant acetohydroxyacid isomeroreductase (AHAIR), and overexpression of select glycolytic genes. Using oleyl alcohol to continuously extract the isobutanol from reaction mixture and tripling the cell concentration in the reaction mixture to 60 g dry cell/L stretched the yield to 78.1% and volumetric productivity to 981 mM (9.1% v/v). Biotechnol. Bioeng. 2013;110: 2938–2948. © 2013 Wiley Periodicals, Inc.
Technique optimization of orbital atherectomy in calcified peripheral lesions of the lower extremities
Authors: Das Tony , Mustapha Jihad , Indes Jeffrey , Vorhies Robert , Beasley Robert , Doshi Nilesh , Adams George L. 
Published: June 2013

ObjectivesThe purpose of CONFIRM registry series was to evaluate the use of orbital atherectomy (OA) in peripheral lesions of the lower extremities, as well as optimize the technique of OA.BackgroundMethods of treating calcified arteries (historically a strong predictor of treatment failure) have improved significantly over the past decade and now include minimally invasive endovascular treatments, such as OA with unique versatility in modifying calcific lesions above and below‐the‐knee.MethodsPatients (3135) undergoing OA by more than 350 physicians at over 200 US institutions were enrolled on an “all‐comers” basis, resulting in registries that provided site‐reported patient demographics, ABI, Rutherford classification, co‐morbidities, lesion characteristics, plaque morphology, device usage parameters, and procedural outcomes.ResultsTreatment with OA reduced pre‐procedural stenosis from an average of 88–35%. Final residual stenosis after adjunctive treatments, typically low‐pressure percutaneous transluminal angioplasty (PTA), averaged 10%. Plaque removal was most effective for severely calcified lesions and least effective for soft plaque. Shorter spin times and smaller crown sizes significantly lowered procedural complications which included slow flow (4.4%), embolism (2.2%), and spasm (6.3%), emphasizing the importance of treatment regimens that focus on plaque modification over maximizing luminal gain.ConclusionThe OA technique optimization, which resulted in a change of device usage across the CONFIRM registry series, corresponded to a lower incidence of adverse events irrespective of calcium burden or co‐morbidities. © 2013 The Authors. Wiley Periodicals, Inc.
Multiple Tank Explosions in an Edible‐Oil Refinery Plant: A Case Study
Authors: Marmo L. , Piccinini N. , Russo G. , Russo P. , Munaro L. 
Published: June 2013

AbstractMultiple explosions occurred when five workers were acting on a footbridge structure at the top of crude olive pomace oil tanks. Welding on the tank roofs was performed without previously cleaning the tanks stopping their operation. First, one of the several ∼ 650‐m3 reservoirs exploded, provoking a pool fire that spread throughout the tank farm. Roughly 1 h later, two other reservoirs exploded causing the launching of missiles to a distance of 60–80 m and a huge fire that extended throughout the entire tank farm. Four workers were killed instantaneously. The explosion was caused by the unusually high content of hexane in the crude olive pomace oil and, hence, by the inefficiency of the desolventization process which creates a flammable and explosive oil from a combustible one.
Transporting and Shielding Photosensitisers by Using Water‐Soluble Organometallic Cages: A New Strategy in Drug Delivery and Photodynamic Therapy
Authors: Therrien Bruno 
Published: June 2013

AbstractSkin photosensitivity remains one of the main limitations in photodynamic therapy. In this Concept article a strategy to overcome this limitation is described, in which the photosensitizer is hidden inside the hydrophobic cavity of a water‐soluble organometallic cage. The metallacage not only protects the photosensitizer from light, it also facilitates its delivery to cancer cells.
PCR‐basierte Methode zur Bestimmung von Gen‐Mutationen
Authors: Fuchs Jan , Schlesiger Ralf , Lehmann Leane 
Published: June 2013

AbstractChemikalien, Biozide, Pflanzenschutzmittel oder Pharmazeutika, die Mutationen induzieren, können auch ein kanzerogenes Potential besitzen. Die Sicherheitsbewertung dieser Stoffe muss daher Kenntnis über ihre Mutagenität liefern. Hierzu wurde ein Genotyp‐selektives Testsystem entwickelt.
Koffein stärkt Gedächtnis der Bienen
Authors: Groß Michael 
Published: June 2013

AbstractWenn Pflanzen psychoaktive Alkaloide wie Nikotin, Kokain oder Koffein produzieren, dann liegt deren natürliche Funktion meist in der Abwehr von Schädlingen. Erst jetzt wurde für pflanzliches Koffein ein völlig anderer Nutzen entdeckt: in den Blüten dient es offenbar der Manipulation des Verhaltens der Bienen.