bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of several protein a resins for application to multicolumn chromatography for the rapid purification of fed‐batch bioreactors
Authors: Hilbold Nicolas‐Julian , Le Saoût Xavier , Valery Eric , Muhr Laurence , Souquet Jonathan , Lamproye Alain , Broly Hervé 
Published: April 2017

Most of the existing production capacity is based on fed‐batch bioreactors. Thanks to the development of more efficient cell lines and the development of high‐performance culture media, cell productivity dramatically increased. In a manufacturing perspective, it is necessary to clear as quickly as possible the protein A capture step to respect the manufacturing agenda. This article describes the methodology applied for the design of a multicolumn chromatography process with the objective of purifying as quickly as possible 1,000 and 15,000 L fed‐batch bioreactors. Several recent and reference protein A resins are compared based on characteristic values obtained from breakthrough curves. The importance and relevance of resin parameters are explained, and purposely simple indicators are proposed to quickly evaluate the potential of each candidate. Based on simulation data, the optimum BioSC systems associated with each resin are then compared. The quality of the elution delivered by each resin is also compared to complete the assessment. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:941–953, 2017
A nonchromatographic process for purification of secretory immunoglobulins from caprine whey
Authors: Matlschweiger Alexander , Himmler Gottfried , Linhart Clemens , Harasek Michael , Hahn Rainer 
Published: April 2017

Secretory immunoglobulins are an important antibody class being primarily responsible for immunoprotection of mucosal surfaces. A simple, non‐chromatographic purification process for secretory immunoglobulins from caprine whey was developed. In the first process step whey was concentrated 30–40‐fold on a 500 kDa membrane, thereby increasing the purity from 3% to 15%. The second step consisted of a fractionated PEG precipitation, in which high molecular weight impurities were removed first and in the second stage the secretory immunoglobulins were precipitated, leaving a majority of the low molecular weight proteins in solution. The re‐dissolved secretory immunoglobulin fraction had a purity of 43% which could then be increased to 72% by diafiltration at a volume exchange factor of 10. Further increase of purity was only possible at the expense of very high buffer consumption. If diafiltration was performed directly after ultrafiltration, followed by precipitation, the yield was higher but purity was only 54%. Overall, filtration performance was characterized by high concentration polarization, therefore process conditions were set to low trans‐membrane pressure and moderate protein concentration. As such purity and to a lesser extent throughput were the major objectives rather than yield, since whey, as a by‐product of the dairy industry, is a cheap raw material of almost unlimited supply. Ultra‐/diafiltration performance was described well by correlations using dimensionless numbers. Compared with a theoretical model (Graetz/Leveque solution) the flux was slightly overestimated. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:642–653, 2017
Principles and approach to developing mammalian cell culture media for high cell density perfusion process leveraging established fed‐batch media
Authors: Lin Henry , Leighty Robert Woodrow , Godfrey Scott , Wang Samantha Boran 
Published: April 2017

Perfusion medium was successfully developed based on our fed‐batch platform basal and feed media. A systematic development approach was undertaken by first optimizing the ratios of fed‐batch basal and feed media followed by targeted removal of unnecessary and redundant components. With this reduction in components, the medium could then be further concentrated by 2× to increase medium depth. The medium osmolality was also optimized where we found ∼360 mOsm/kg was desirable resulting in a residual culture osmolality of ∼300 mOsm/kg for our cell lines. Further building on this, the amino acids Q, E, N, and D were rebalanced to reduce lactate and ammonium levels, and increase the cell‐specific productivity without compromising on cell viability while leaving viable cell density largely unaffected. Further modifications were also made by increasing certain important vitamin and lipid concentrations, while eliminating other unnecessary vitamins. Overall, an effective perfusion medium was developed with all components remaining in the formulation understood to be important and their concentrations increased to improve medium depth. The critical cell‐specific perfusion rate using this medium was then established for a cell line of interest to be 0.075 nL/cell‐day yielding 1.2 g/L‐day at steady state. This perfusion process was then successfully scaled up to a 100 L single‐use bioreactor with an ATF6 demonstrating similar performance as a 2 L bioreactor with an ATF2. Large volume handling challenges in our fed‐batch facility were overcome by developing a liquid medium version of the powder medium product contained in custom totes for plug‐and‐play use with the bioreactor. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:891–901, 2017
Influence of mixed electrolytes on the adsorption of lysozyme, PEG, and PEGylated lysozyme on a hydrophobic interaction chromatography resin
Authors: Hackemann Eva , Werner Albert , Hasse Hans 
Published: April 2017

In a recent work (Werner A and Hasse H in J Chromatogr A 2013;1315:135) the influence of mixed electrolytes on the adsorption of the macromolecules lysozyme, PEG and di‐PEGylated lysozyme on a hydrophobic resin has been studied, but only at one overall ionic strength (3000 mM). The present work, therefore, extends these studies to other ionic strengths (2400 and 2700 mM), and explores the application of a model to predict the entire data set. The adsorbent is Toyopearl PPG‐600M. The solvent is a 25 mM aqueous sodium phosphate buffer at pH 7.0. The studied salts are sodium chloride, sodium sulfate, ammonium chloride and ammonium sulfate. Pure salts as well as binary and ternary mixtures of these salts with varying ratios of the amounts of the salts are studied at 25 °C. The loading of the adsorbent increases with increasing salt concentration for all macromolecules. Synergetic effects of the mixed electrolytes are observed. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1104–1115, 2017
The positive clinical therapeutically effects of Escin on advanced thyroid cancer
Authors: Mei Jin‐Yu , Zhang Ming‐Jun , Wang Yuan‐Yuan , Liu Ye‐Hai 
Published: April 2017

AbstractThe incidences of thyroid cancer keep rising worldwide over the past few decades. Although most thyroid cancers are indolent and highly curable, the treatment for advanced thyroid cancer remains challengeable in clinical practice. We performed two separate cohorts to evaluate the safety and efficiency of Escin in patients with advanced thyroid cancer . In cohort 1, 120 patients were divided into four groups equally and were administrated with placebo or different dosages of Escin. The pharmacokinetics of Escin and the side effects were evaluated. In cohort 2, 120 patients were treated with Escin. Several biomarkers related to the progression of thyroid cancer were evaluated. Kaplan–Meier (KM) analyses were performed to evaluate progression‐free survival (PFS) and overall survival (OS). The serum Escin concentrations were stable during the treatment. Escin (0.6 mg/kg/day for 9 days, intravenous injection) was tolerable for patients with thyroid cancer . Escin significantly reduced the serum levels of TSH, TgAb, Tg, and calcitonin and prolonged the PFS and OS for patients with advanced thyroid cancer. This study showed Escin is efficient and well tolerated in patients with advanced thyroid cancer. Future studies are needed to investigate the mechanism of Escin on thyroid cancer and the proper dosage of Escin clinically.
CCR7 mediates human breast cancer cell invasion, migration by inducing epithelial–mesenchymal transition and suppressing apoptosis through AKT pathway
Authors: Xu Bing , Zhou Minjie , Qiu Wencai , Ye Jueming , Feng Qiming 
Published: April 2017

AbstractChemokine and the chemokine receptor have a key role in the tumor progress. Here, we supposed that CCR7 might induce the invasion, migration, and epithelial–mesenchymal transition (EMT) process of breast cancer. In this research, human breast cancer MCF‐7 and MDA‐MB‐231cells were treated with CCL19 and small‐interfering RNA (CCR7 siRNA) for activation and inhibition of CCR7, respectively. Cell invasion and transwell assays were used to detect the effect of CCR7 on invasion and migration. The results demonstrated that CCL19 mediated cell invasion and migration by inducing the EMT, with downregulation of E‐cadherin and up‐regulation of N‐cadherin and vimentin levels. On the other hand, knockdown of CCR7 revealed the changes compared with CCL19 group and the control group. Knockdown of CCR7 inhibits CCL19‐induced breast cancer cell proliferation, the cell cycle, migration, invasion and EMT. Moreover, we demonstrated that CCL19‐induced AKT phosphorylation; however, CCR7 siRNA suppressed CCL19‐induced AKT phosphorylation, a key regulator of tumor metastasis. In conclusion, all findings demonstrated that CCL19/CCR7 axis regulated EMT progress in breast cancer cells and mediated the tumor cell invasion and migration process via activation of AKT signal pathway. Our results suggested that CCR7 may regard as a therapeutic target for the breast cancer treatment.
DNA methylation epigenotype and clinical features of NRAS‐mutation(+) colorectal cancer
Authors: Takane Kiyoko , Akagi Kiwamu , Fukuyo Masaki , Yagi Koichi , Takayama Tadatoshi , Kaneda Atsushi 
Published: April 2017

AbstractSporadic colorectal cancer (CRC) is classified into several molecular subtypes. We previously established two groups of DNA methylation markers through genome‐wide DNA methylation analysis to classify CRC into distinct subgroups: high‐, intermediate‐, and low‐methylation epigenotypes (HME, IME, and LME, respectively). HME CRC, also called CpG island methylator phenotype (CIMP)‐high CRC, shows methylation of both Group 1 markers (CIMP markers) and Group 2 markers, while IME/CIMP‐low CRC shows methylation of Group 2, but not of Group 1 markers, and LME CRC shows no methylation of either Group 1 or Group 2 markers. While BRAF‐ and KRAS‐mutation(+) CRC strongly correlated with HME and IME, respectively, clinicopathological features of NRAS‐mutation(+) CRC, including association with DNA methylation, remain unclear. To characterize NRAS‐mutation(+) CRC, the methylation levels of 19 methylation marker genes (6 Group 1 and 13 Group 2) were analyzed in 61 NRAS‐mutation(+) and 144 NRAS‐mutation(−) CRC cases by pyrosequencing, and their correlation with clinicopathological features was investigated. Different from KRAS‐mutation(+) CRC, NRAS‐mutation(+) CRC significantly correlated with LME. NRAS‐mutation(+) CRC showed significantly better prognosis than KRAS‐mutation(+) CRC (P = 3 × 10−4). NRAS‐mutation(+) CRC preferentially occurred in elder patients (P = 0.02) and at the distal colon (P = 0.006), showed significantly less lymph vessel invasion (P = 0.002), and correlated with LME (P = 8 × 10−5). DNA methylation significantly accumulated at the proximal colon. NRAS‐mutation(+) CRC may constitute a different subgroup from KRAS‐mutation(+) CRC, showing significant correlation with LME, older age, distal colon, and relatively better prognosis.
AzaGly‐Appended Peptidomimetics Structurally Related to PTR6154 as Potential PKB/Akt Inhibitors
Authors: Singh Shalini , Shrivastava Richa , Singh Gajendra , Ali Rafat , Sankar Ampapathi Ravi , Bhadhuria Smrati , Haq Wahajul 
Published: April 2017

AbstractWe report the synthesis and biological and physiochemical properties of a series of azaGly‐appended peptidomimetics. We have developed a simple and facile synthesis for azapeptides on solid support without any side reaction. The azaGly is inserted by in situ reaction of disuccinimidyl carbonate with free amine followed by treatment of hydrazine hydrate at room temperature. The new series of peptidomimetics was prepared by azaGly scanning of heptapeptide Arg‐Pro‐Arg‐Nle‐Tyr‐Dap‐Nle (Akt‐01), a GSK‐3β‐derived Akt inhibitor. The azaGly‐appended peptides showed significant improvement in biological activity and serum stability, with retention of conformation as evidenced by NMR and CD studies. The results clearly demonstrate that azaGly‐appended peptides are new peptidomimetics. Their synthesis makes this approach highly useful for the development of novel peptidomimetics of therapeutic potential.
AG490 suppresses interleukin‐34‐mediated osteoclastogenesis in mice bone marrow macrophages
Authors: Cheng Xin , Wan Qi‐Long , Li Zu‐Bing 
Published: April 2017

AbstractInterleukin‐34 (IL‐34) has been recently identified as a novel cytokine, substituting for the function of macrophage colony‐stimulating factor (M‐CSF), a pivotal osteoclastogenic factor involved in bone‐related diseases (e.g., osteomyelitis of the jaws). However, the molecular mechanisms are not fully understood. This study aimed to explore the potential mechanism of IL‐34 in receptor activator of NF‐kB ligand (RANKL)‐induced osteoclast formation. We found that IL‐34 alone significantly maintained the survival of bone marrow macrophages (BMMs) and enhanced the expression of the osteoclast‐related genes TRAP, Ctsk, and NFATc1, as well as TRAP‐positive multinucleated cells combined with RANKL, which can be reversed by AG490. Conversely, AG490 did not affect the M‐CSF‐mediated osteoclastogenesis in the presence of RANKL. The protein expression of p‐STAT3 in BMMs was enhanced by IL‐34 combined with RANKL compared with RANKL alone, and AG490 inhibited the expression of p‐SATA3 at protein level in the IL‐34 plus RANKL group, resulting in significantly increased Smad7 expression. This study demonstrated for the first time that IL‐34 may play a crucial role in RANKL‐induced osteoclastogenesis by promoting the proliferation and differentiation of BMMs, stimulating p‐STAT3 expression, and inhibiting the expression of Smad7 in the absence of M‐CSF.
Surfer's ear
Authors: Okuyama Yumi , Baba Akira , Ojiri Hiroya , Nakajima Tsuneya 
Published: April 2017

Key Clinical MessageExostosis in external auditory canal is common among surfers. Common symptoms are decreased hearing or loss of hearing, ear infection, and/or plugging sensation. Repeated exposure to cold water is a key clinical history to suspect this condition. Based on symptoms and existence of infection, surgical removal of the exostosis is recommended.
The Influence of Operation Temperature and Variations of the Illumination on the Performance of Integrated Photoelectrochemical Water‐Splitting Devices
Authors: Welter Katharina , Smirnov Vladimir , Becker Jan‐Philipp , Borowski Patrick , Hoch Sascha , Maljusch Artjom , Jaegermann Wolfram , Finger Friedhelm 
Published: April 2017

AbstractRenewable and storable fuel hydrogen can be produced through light‐driven water splitting using photovoltaic‐biased electrosynthetic (PV‐EC) devices. The required voltage to drive the reaction is approximately 1.5 V, which can be provided using multi‐junction silicon solar cells. To generate these voltages at the operation point, the solar cells are electrically optimized with respect to the standard test conditions. However, if such devices were to be used outdoors, a wide range of different illumination conditions has to be considered. Herein, we discuss the dependence of the solar‐to‐hydrogen efficiency on the spectral quality, the incident illumination intensity and the operation temperature. It is found that in the case of high irradiation intensities (e. g. 1 sun), high operation temperatures reduce the PV performance, but the overall PV‐EC device performance remains almost unchanged due to improved kinetics in the EC part. In contrast, when the illumination intensity is reduced, the loss in PV performance cannot be compensated by improved EC performances due to higher temperatures.
Formation of Fe3O4 Nanoparticles Embedded in an Olive‐Shaped Carbon Skeleton as a High‐Performance Anode Material
Authors: Yao Xiufeng , Yang Zhanxu , Qi Chengyuan , Li Yue , Cai Tianfeng , Ren Tieqiang 
Published: April 2017

AbstractFe3O4 is a potential anode material for lithium‐ion batteries, because of its environmentally friendliness, high capacity, and inexpensive availability. However, Fe3O4 causes a severe capacity attenuation, owing to a large volume change, and it has a poor rate capability, owing to low conductivity. In this work, Fe3O4 nanoparticles embedded in an olive‐shaped carbon skeleton were prepared through the one‐step pyrolysis of metal‐organic framework (MOF) precursors in a nitrogen atmosphere. The Fe3O4 nanoparticles were evenly embedded in the olive‐shaped carbon skeleton and the Fe3O4 particle size was around 23 nm in width and 38 nm in length, which exhibits enhanced cycling and rate performance. The prepared Fe3O4/C material achieves a high initial charge and discharge capacity of 1423.0 mAhg−1 and 925.5 mAhg−1, respectively, and shows a remarkable cycle‐stable specific capacity of 877.0 mAhg−1 after 80 cycles at 0.5 C. High specific discharge capacities of 810, 720, 660, 585, 516, 486, and 460 mAhg−1 were obtained at 0.5, 1, 2, 6, 12, 15, and 20 C, respectively.
Anodic Chlorination of Selenophene‐Containing Polymers: Reaction Efficiency and Selective Reaction of Single Segment in Rod−Rod Diblockcopolymer
Authors: Shida Naoki , Okazaki Daichi , Kurioka Tomoyuki , Nishiyama Hiroki , Seferos Dwight S. , Tomita Ikuyoshi , Inagi Shinsuke 
Published: April 2017

AbstractThe post‐polymerization modification of selenophene‐containing (co)polymers is presented based on the electrochemical polymer reaction (ECPR). Selenophene‐ or thiophene‐containing (co)polymers, which are known to be promising materials in optoelectronic devices, were synthesized through Kumada catalyst transfer polymerization to give their homopolymers and block‐ or statistical copolymers with various side chains. Each of the series of polymers was subjected to post‐modification through the ECPR, and the reaction efficiencies were systematically compared. Selenophene‐containing polymers were successfully modified with better ECPR reaction efficiencies than their thiophene analogues. Moreover, the dramatic inhibiting effect of a branched side chain on the ECPR was observed and rationalized, which was very unexpected. Based on the basic tendency observed here, we have finally demonstrated the selective modification of a single segment of a rod−rod block copolymer for the first time.
Improved Lithium‐Ion and Sodium‐Ion Storage Properties from Few‐Layered WS2 Nanosheets Embedded in a Mesoporous CMK‐3 Matrix
Authors: Pang Qiang , Gao Yu , Zhao Yingying , Ju Yanming , Qiu Hailong , Wei Yingjin , Liu Bingbing , Zou Bo , Du Fei , Chen Gang 
Published: April 2017

AbstractAn integrated WS2@CMK‐3 nanocomposite has been prepared by a one‐step hydrothermal method and then used as the anode material for lithium‐ion and sodium‐ion batteries. Ultrathin WS2 nanosheets have been successfully embedded into the ordered mesoporous carbon (CMK‐3) framework. Owing to the few‐layered nanostructure of WS2, as well as the high electronic conductivity and the volume confinement effect of CMK‐3, the material shows larger discharge capacity, better rate capability, and improved cycle stability than pristine WS2. When tested in lithium‐ion batteries, the material delivers a reversible capacity of 720 mA h g−1 after 100 cycles at a current density of 100 mA g−1. A large discharge capacity of 307 mA h g−1 is obtained at a current density of 2 A g−1. When used in sodium‐ion batteries, the material exhibits a capacity of 333 mA h g−1 at 100 mA g−1 without capacity fading after 70 cycles. A discharge capacity of 230 mA h g−1 is obtained at 2 A g−1. This excellent performance demonstrates that the WS2@CMK‐3 nanocomposite has great potential as a high‐performance anode material for next‐generation rechargeable batteries.
Solid‐State NMR Spectroscopy Proves the Presence of Penta‐coordinated Sc Sites in MIL‐100(Sc)
Authors: Giovine Raynald , Volkringer Christophe , Ashbrook Sharon E. , Trébosc Julien , McKay David , Loiseau Thierry , Amoureux Jean‐Paul , Lafon Olivier , Pourpoint Frédérique 
Published: April 2017

AbstractAdvanced solid‐state NMR methods and first‐principles calculations demonstrate for the first time the formation of penta‐coordinated scandium sites. These coordinatively unsaturated sites were shown during the thermal activation of scandium‐based metal‐organic frameworks (MOFs). A 45Sc NMR experiment allows their specific observation in activated Sc3BTB2 (H3BTB=1,3,5‐tris(4‐carboxyphenyl)benzene) and MIL‐100(Sc) MOFs. The assignment of the ScO5 groups is supported by the DFT calculations of NMR parameters. The presence of ScO5 Lewis acid sites in MIL‐100(Sc) explains furthermore its catalytic activity. The first NMR experiment to probe 13C−45Sc distances is also introduced. This advanced solid‐state NMR pulse sequence allows the demonstration of the shrinkage of the MIL‐100(Sc) network when the activation temperature is raised.
Assessing How Correlated Molecular Orbital Calculations Can Perform versus Kohn–Sham DFT: Barrier Heights/Isomerizations
Authors: Varandas António J. C. , Martínez González Marco , Montero‐Cabrera Luis A. , Garcia de la Vega José M. 
Published: April 2017

AbstractTo assess the title issue, 38 hydrogen transfer barrier heights and 38 non‐hydrogen transfer barrier heights/isomerizations extracted from extensive databases have been considered, in addition to 4 2 p‐isomerization reactions and 6 others for large organic molecules. All Kohn–Sham DFT calculations have employed the popular M06‐2X functional, whereas the correlated molecular orbital (MO)‐based ones are from single‐reference MP2 and CCSD(T) methods. They have all utilized the same basis sets, with raw MO energies subsequently extrapolated to the complete basis set limit without additional cost. MP2 calculations are found to be as cost‐effective as DFT ones and often slightly more, while showing a satisfactory accuracy when compared with the reference data. Although the focus is on barrier heights, the results may bear broader implications, in that one may see successes and difficulties of DFT when compared with traditional MO theories for the same data.
Supramolecular Hydrogels Based on Minimalist Amphiphilic Squaramide–Squaramates for Controlled Release of Zwitterionic Biomolecules
Authors: López Carlos , Ximenis Marta , Orvay Francisca , Rotger Carmen , Costa Antonio 
Published: April 2017

AbstractSupramolecular hydrogels with tunable properties have innovative applications in biomedicine, catalysis, and materials chemistry. Minimalist low‐molecular‐weight hydrogelators based on squaramide and squaramic acid motifs have been designed. This approach benefits from the high acidity of squaramic acids and the aromaticity of squaramides. Moreover, substituents on the aryl ring tune the π density of the arylsquaramide motif. Thus, materials featuring distinct thermal and mechanical properties have been successfully prepared. The hydrogel (G′≈400 Pa, G′′≈57 Pa; at 1.0 % w/v; 1 Hz) obtained from 4‐nitrophenylsquaramide motif 1 is thermoreversible (T=57 °C at 0.2 % w/v), thixotropic, self‐healable, and undergoes irreversible shrinking in response to saline stress. Furthermore, the hydrogel is injectable and can be loaded with substantial amounts (5:1 excess molar ratio) of zwitterionic biomolecules, such as l‐carnitine, γ‐aminobutyric acid (GABA), or d,l‐Ala‐d,l‐Ala, without any loss of structural integrity. Then, the release of these molecules can be modulated by saline solutions.