bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal stability of end‐capped and linear sulfonated polyimides, sulfonated polystyrene, and Nafion 117
Authors: Gong Chenliang , Pinatti Laura , Lavigne Gary , Shaw Montgomery T. , Scola Daniel A. 
Published: September 2017

ABSTRACTThe thermal stability of end‐caped and linear sulfonated polyimides (SPIs), sulfonated polystyrene (SPS), and a sulfonated perfluorinated hydrocarbon, Nafion 117, and the corresponding triethylammonium sulfonate salts was investigated by dynamic and isothermal thermogravimetric analysis (TGA). Gas chromatographic‐mass spectrographic analysis (GC/MS) of the sulfonated polymers and the salts to determine the volatiles released from acid and salt groups over a temperature range 200–275 °C was also investigated. GC/MS analysis reveals that water and sulfur dioxide volatiles are released from the sulfonic acids and water, sulfur dioxide and triethyl amine are released from the sulfonate salts. Dynamic and isothermal TGA studies based on weight loss revealed that the SPIs exhibited superior thermal stability than SPS and Nafion 117 sulfonic acids. However, dynamic TGA curves to determine the onset decomposition temperature of the sulfonic acid group reveal that Nafion 117 and SPS sulfonic acids exhibited greater thermal stabilities than the SPIs. The mechanisms of sulfonic acid and triethylammonium sulfonate salt decompositions based on GC/MS, 13C‐NMR, and dynamic TGA curves are proposed. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45694.
Impact of enzalutamide and its main metabolite N‐desmethyl enzalutamide on pharmacokinetically important drug metabolizing enzymes and drug transporters
Authors: Weiss Johanna , Kocher Jutta , Mueller Corina , Rosenzweig Stephanie , Theile Dirk 
Published: September 2017

AbstractEnzalutamide is a new drug against castration‐resistant prostate cancer. Recent data indicate profound induction of drug metabolizing enzymes (e.g. cytochrome P450 isoenzyme (CYP) 3A4) but comprehensive in vitro data on other CYP enzymes, drug conjugating enzymes or drug transporters is scarce. Moreover, the mechanisms of induction are poorly investigated and the effects of the active metabolite N‐desmethyl enzalutamide are unknown. Using LS180 cells as an induction model and quantitative real‐time reverse transcription polymerase chain reaction, our study demonstrated a concentration‐dependent induction of CYP1A1, CYP1A2, CYP3A5, CYP3A4, UGT1A3, UGT1A9, ABCB1, ABCC2 and ABCG2 mRNA. Induction of CYP3A4 and ABCB1 was confirmed by Western blot analysis and is likely mediated by activation of the nuclear receptor pregnane x receptor, elucidated by a luciferase‐based reporter gene assay. Enzalutamide's main active metabolite N‐desmethyl enzalutamide exhibited only weak induction properties. mRNA expression of UGT2B7 was suppressed by enzalutamide and its metabolite. Both compounds are apparently not transported by P‐glycoprotein (P‐gp) or breast cancer resistance protein (BCRP). N‐desmethyl enzalutamide more potently inhibited important drug transporters (P‐gp, BCRP, OATPs) than enzalutamide. Taken together, the pharmacokinetics of concurrently administered drugs is likely altered during enzalutamide therapy. Levels of metabolically (mainly CYP3A4) eliminated drugs are expected to be decreased, whereas the abundance of compounds with solely transporter‐determined pharmacokinetics (P‐gp, OATPs) is likely enhanced.
Development of a general defined medium for Pichia pastoris
Authors: Matthews Catherine B. , Kuo Angel , Love Kerry R. , Love J. Christopher 
Published: September 2017

AbstractPichia pastoris is widely used as a host for recombinant protein production. More than 500 proteins have been expressed in the organism at a variety of cultivation scales, from small shake flasks to large bioreactors. Large‐scale fermentation strategies typically employ chemically defined growth medium because of its greater batch‐to‐batch consistency and in many cases, lower costs compared to complex medium. For biopharmaceuticals, defined growth medium may also simplify downstream purification and regulatory documentation. Standard formulations of defined media for P. pastoris are minimal ones that lack the metabolic intermediates provided by complex components such as peptone and yeast extract. As a result, growth rates and per‐cell productivities are significantly lower than in complex medium. We have designed a rich defined medium (RDM) for Pichia pastoris by systematically evaluating nutrients of increasing complexity and identifying those that are most critical for growth. We have also employed transcriptomics to gain deeper insights into the underlying metabolic processes and inform our media design. We have demonstrated that using RDM for expression of three heterologous proteins yields titers comparable to, or higher than, those in standard complex medium. RDM improves productivity of P. pastoris fermentations and its development demonstrates the usefulness of transcriptomics to accelerate process development for new molecules.
Countercurrent staged diafiltration for formulation of high value proteins
Authors: Nambiar Anirudh M. K. , Li Ying , Zydney Andrew L. 
Published: September 2017

AbstractA number of groups have studied the application of continuous bioreactors and continuous chromatographic systems as part of efforts to develop an integrated continuous biomanufacturing process. The objective of this study was to examine the feasibility of using a countercurrent staged diafiltration process for continuous protein formulation with reduced buffer requirements. Experiments were performed using a polyclonal immunoglobulin (IgG) with Cadence™ Inline Concentrators. Model equations were developed for the product yield, impurity removal, and buffer requirements as a function of the number of stages and the stage conversion (ratio of permeate to feed flow rate). Data from a countercurrent two‐stage system were in excellent agreement with model calculations, demonstrating the potential of using countercurrent staged diafiltration for protein formulation. Model simulations demonstrated the importance of the countercurrent staging on both the extent of buffer exchange and the amount of buffer required per kg of formulated product. The staged diafiltration process not only provides for continuous buffer exchange, it could also provide significant reductions in the number of pump passes while providing opportunities for reduced buffer requirements.
Dry biorefining maximizes the potentials of simultaneous saccharification and co‐fermentation for cellulosic ethanol production
Authors: Liu Gang , Zhang Qiang , Li Hongxing , Qureshi Abdul S. , Zhang Jian , Bao Xiaoming , Bao Jie 
Published: September 2017

AbstractDespite the well‐recognized merits of simultaneous saccharification and co‐fermentation (SSCF) on relieving sugar product inhibition on cellulase activity, a practical concomitance difficulty of xylose with inhibitors in the pretreated lignocellulose feedstock prohibits the essential application of SSCF for cellulosic ethanol fermentation. To maximize the SSCF potentials for cellulosic ethanol production, a dry biorefining approach was proposed starting from dry acid pretreatment, disk milling, and biodetoxification of lignocellulose feedstock. The successful SSCF of the inhibitor free and xylose conserved lignocellulose feedstock after dry biorefining reached a record high ethanol titer at moderate cellulase usage and minimum wastewater generation. For wheat straw, 101.4 g/L of ethanol (equivalent to 12.8% in volumetric percentage) was produced with the overall yield of 74.8% from cellulose and xylose, in which the xylose conversion was 73.9%, at the moderate cellulase usage of 15 mg protein per gram cellulose. For corn stover, 85.1 g/L of ethanol (equivalent to 10.8% in volumetric percentage) is produced with the overall conversion of 84.7% from cellulose and xylose, in which the xylose conversion was 87.7%, at the minimum cellulase usage of 10 mg protein per gram cellulose. Most significantly, the SSCF operation achieved the high conversion efficiency by generating the minimum amount of wastewater. Both the fermentation efficiency and the wastewater generation in the current dry biorefining for cellulosic ethanol production are very close to that of corn ethanol production, indicating that the technical gap between cellulosic ethanol and corn ethanol has been gradually filled by the advancing biorefining technology.
Temperature‐dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli
Authors: Harder Björn‐Johannes , Bettenbrock Katja , Klamt Steffen 
Published: September 2017

AbstractBased on the recently constructed Escherichia coli itaconic acid production strain ita23, we aimed to improve the productivity by applying a two‐stage process strategy with decoupled production of biomass and itaconic acid. We constructed a strain ita32 (MG1655 ΔaceA Δpta ΔpykF ΔpykA pCadCs), which, in contrast to ita23, has an active tricarboxylic acid (TCA) cycle and a fast growth rate of 0.52 hr−1 at 37°C, thus representing an ideal phenotype for the first stage, the growth phase. Subsequently we implemented a synthetic genetic control allowing the downregulation of the TCA cycle and thus the switch from growth to itaconic acid production in the second stage. The promoter of the isocitrate dehydrogenase was replaced by the Lambda promoter (pR) and its expression was controlled by the temperature‐sensitive repressor CI857 which is active at lower temperatures (30°C). With glucose as substrate, the respective strain ita36A grew with a fast growth rate at 37°C and switched to production of itaconic acid at 28°C. To study the impact of the process strategy on productivity, we performed one‐stage and two‐stage bioreactor cultivations. The two‐stage process enabled fast formation of biomass resulting in improved peak productivity of 0.86 g/L/hr (+48%) and volumetric productivity of 0.39 g/L/hr (+22%) in comparison to the one‐stage process. With our dynamic production strain, we also resolved the glutamate auxotrophy of ita23 and increased the itaconic acid titer to 47 g/L. The temperature‐dependent activation of gene expression by the Lambda promoters (pR/pL) has been frequently used to improve protein or, in a few cases, metabolite production in two‐stage processes. Here we demonstrate that the system can be as well used in the opposite direction to selectively knock‐down an essential gene (icd) in E. coli to design a two‐stage process for improved volumetric productivity. The control by temperature avoids expensive inducers and has the potential to be generally used to improve cell factory performance.
Power input effects on degeneration in prolonged penicillin chemostat cultures: A systems analysis at flux, residual glucose, metabolite, and transcript levels
Authors: Wang Guan , Wu Baofeng , Zhao Junfei , Haringa Cees , Xia Jianye , Chu Ju , Zhuang Yingping , Zhang Siliang , Heijnen Joseph J. , van Gulik Walter , Deshmukh Amit T. , Noorman Henk J. 
Published: September 2017

AbstractIn the present work, by performing chemostat experiments at 400 and 600 RPM, two typical power inputs representative of industrial penicillin fermentation (P/V, 1.00 kW/m3 in more remote zones and 3.83 kW/m3 in the vicinity of the impellers, respectively) were scaled‐down to bench‐scale bioreactors. It was found that at 400 RPM applied in prolonged glucose‐limited chemostat cultures, the previously reported degeneration of penicillin production using an industrial Penicillium chrysogenum strain was virtually absent. To investigate this, the cellular response was studied at flux (stoichiometry), residual glucose, intracellular metabolite and transcript levels. At 600 RPM, 20% more cell lysis was observed and the increased degeneration of penicillin production was accompanied by a 22% larger ATP gap and an unexpected 20‐fold decrease in the residual glucose concentration (Cs,out). At the same time, the biomass specific glucose consumption rate (qs) did not change but the intracellular glucose concentration was about sixfold higher, which indicates a change to a higher affinity glucose transporter at 600 RPM. In addition, power input differences cause differences in the diffusion rates of glucose and the calculated Batchelor diffusion length scale suggests the presence of a glucose diffusion layer at the glucose transporting parts of the hyphae, which was further substantiated by a simple proposed glucose diffusion‐uptake model. By analysis of calculated mass action ratios (MARs) and energy consumption, it indicated that at 600 RPM glucose sensing and signal transduction in response to the low Cs,out appear to trigger a gluconeogenic type of metabolic flux rearrangement, a futile cycle through the pentose phosphate pathway (PPP) and a declining redox state of the cytosol. In support of the change in glucose transport and degeneration of penicillin production at 600 RPM, the transcript levels of the putative high‐affinity glucose/hexose transporter genes Pc12g02880 and Pc06g01340 increased 3.5‐ and 3.3‐fold, respectively, and those of the pcbC gene encoding isopenicillin N‐synthetase (IPNS) were more than twofold lower in the time range of 100–200 hr of the chemostat cultures. Summarizing, changes at power input have unexpected effects on degeneration and glucose transport, and result in significant metabolic rearrangements. These findings are relevant for the industrial production of penicillin, and other fermentations with filamentous microorganisms.
On the Electronic Origin of Remarkable Ligand Effects on the Reactivities of [NiL]+ Complexes (L=C6H5, C5H4N, CN) towards Methane
Authors: Zhou Shaodong , Firouzbakht Marjan , Schlangen Maria , Kaupp Martin , Schwarz Helmut 
Published: September 2017

AbstractThe gas‐phase reactions of [NiL]+ (L=C6H5, C5H4N, CN) with methane have been explored by using electrospray‐ionization mass spectrometry (ESI‐MS) complemented by quantum chemical calculations. Though the phenyl Ni complex [Ni(C6H5)]+ exclusively abstracts one hydrogen atom from methane at ambient conditions, the cyano Ni complex [Ni(CN)]+ brings about both H‐atom abstraction and ligand exchange to generate [Ni(CH3)]+. In contrast, the complex 2‐pyridinyl Ni [Ni(C5H4N)]+ is inert towards this substrate. The presence of the empty 4s(Ni) orbital dominates the proton‐coupled electron transfer (PCET) processes for the investigated systems.
Effect of sorbent reactivity on flue gas desulphurization in fluidized‐bed boilers under air firing mode
Authors: Szymanek Arkadiusz , de las Obras‐Loscertales Margarita , Pajdak Anna 
Published: September 2017

AbstractThe article presents research into the reactivity and SO2 sorption abilities of calcareous sorbents, which vary in quality. Two sorbents were used: limestone and travertine, with grain sizes between 0.125 and 0.250 mm. The sorbent reactivity tests were performed on a laboratory test stand. The reactivity index and the conversion degree were also determined. SO2 sorption studies were conducted in an industrial boiler. The desulphurization efficiency was determined taking into the account the content of calcium and sulphur put into and taken out of the boiler. The relation of the desulphurization process parameters such as fuel sulphur content, stream sorbent, sorbent utilization degree, desulphurization efficiency, depending on the molar ratio Ca/S and the duration of the process was specified. The SO2 sorption results were compared with the reactivity index of the sorbents. The investigation in dry combustion‐gas desulphurization methods showed the high quality of the sorbents whose reactivity index is above 3.5.
Plasmonic Fields Focused to Molecular Size
Authors: Minamimoto Hiro , Oikawa Shunpei , Li Xiaowei , Murakoshi Kei 
Published: September 2017

AbstractEfficient use of light energy is regarded as a key factor in solving energy challenges to create a sustainable society. The highly concentrated photon energy generated by localized surface plasmon resonance excitation in the vicinity of metal nanostructures can enhance light‐matter interaction. Optimization of the interactions between plasmons and electrons in materials can lead to novel light energy applications. To overcome the current limitations for these interactions, the plasmon field must be focused to an extremely small size close to the molecular scale. Formation of the plasmonic field at the quantum limit may cause interesting phenomena with unique photoresponses. Recently, following the development of nanofabrication techniques, detailed investigations have been undertaken to understand these processes. In this focus review, we describe recent advances in the strong interactions between highly localized photons and electrons in nanomaterials, including molecules, nanocarbons, and quantized nanoparticles. First, we outline the plasmonic properties that depend on the metal nanostructures. In addition, we describe surface‐enhanced Raman scattering (SERS), which is used to detect interactions between plasmons and materials. The importance of the resonant electronic excitation process, which is a chemical effect based on the charge transfer contribution, is discussed while considering the unique molecular selectivity in SERS. We then highlight the unique photoresponse properties that are used for ultra‐sensitive detection of single molecules by the localized plasmon field. These properties are major advantages of the plasmon field. Next, we introduce strong coupling between plasmons and excitons. This coupling state is promising because of its ability to modify the intrinsic optical properties of materials via creation of a novel absorption wavelength region to accumulate the light energy. Finally, we discuss the use of plasmon excitation for effective chemical reactions accompanied by electron transfer. We conclude that reduction of light to the molecular scale would open novel routes for energy manipulation required by the next generation.
Surface Engineering Layered Metal–Organic Framework to Enhance Processability and Stability in Water
Authors: Li Yung‐Lin , Chi Heng‐Yu , Kan Ming‐Yang , Pao Szu‐Ying , Kang Yu‐Hao , Chen Jiun‐Jen , Kang Dun‐Yen 
Published: September 2017

AbstractDespite considerable advancements of metal–organic frameworks (MOFs), the practical implementation of MOFs is still hindered by issues of stability and processability. In this work, we sought to overcome these difficulties through surface engineering. As a proof of concept, we subjected ZIF‐L with a unique layered crystal morphology to a shell‐ligand exchange reaction. This resulted in the partial replacement of 2‐methylimidazole by benzimidazole as the linker in the framework on the outer surface of the crystals, thereby changing the surface of the ZIF‐L crystal from hydrophilic to hydrophobic. The engineered ZIF‐L (hereafter referred to as Benz‐ZIF‐L) formed a stable dispersion in the nonpolar solvent, hexane. The suspension of Benz‐ZIF‐L in hexane was applied via spin coating to a porous substrate of poly(vinylidene fluoride) (PVDF), resulting in a thin film of high density. In contrast, the application of a suspension of pure ZIF‐L in the same manner did not result in the formation of a thin film. Benz‐ZIF‐L also exceeded pure ZIF‐L with regard to hydrothermal stability and acid/base resistance.
Centrifugation‐Free Magnetic Isolation of Functional Mitochondria Using Paramagnetic Iron Oxide Nanoparticles
Authors: Banik Bhabatosh , Dhar Shanta 
Published: September 2017

AbstractSubcellular fractionation techniques are essential for cell biology and drug development studies. The emergence of organelle‐targeted nanoparticle (NP) platforms necessitates the isolation of target organelles to study drug delivery and activity. Mitochondria‐targeted NPs have attracted the attention of researchers around the globe, since mitochondrial dysfunctions can cause a wide range of diseases. Conventional mitochondria isolation methods involve high‐speed centrifugation. The problem with high‐speed centrifugation‐based isolation of NP‐loaded mitochondria is that NPs can pellet even if they are not bound to mitochondria. We report development of a mitochondria‐targeted paramagnetic iron oxide nanoparticle, Mito‐magneto, that enables isolation of mitochondria under the influence of a magnetic field. Isolation of mitochondria using Mito‐magneto eliminates artifacts typically associated with centrifugation‐based isolation of NP‐loaded mitochondria, thus producing intact, pure, and respiration‐active mitochondria. © 2017 by John Wiley & Sons, Inc.
Determination of Membrane Protein Distribution on the Nuclear Envelope by Single‐Point Single‐Molecule FRAP
Authors: Mudumbi Krishna C. , Yang Weidong 
Published: September 2017

AbstractNuclear envelope transmembrane proteins (NETs) are synthesized on the endoplasmic reticulum and then transported from the outer nuclear membrane (ONM) to the inner nuclear membrane (INM) in eukaryotic cells. The abnormal distribution of NETs has been associated with many human diseases. However, quantitative determination of the spatial distribution and translocation dynamics of NETs on the ONM and INM is still very limited in currently existing approaches. Here we demonstrate a single‐point single‐molecule fluorescence recovery after photobleaching (FRAP) microscopy technique that enables quick determination of distribution and translocation rates for NETs in vivo. © 2017 by John Wiley & Sons, Inc.
Cellular Detection of G‐Quadruplexes by Optical Imaging Methods
Authors: Amor Souheila , Yang Sunny Y. , Wong Judy M. Y. , Monchaud David 
Published: September 2017

AbstractG‐quadruplexes (G4s) are higher‐order nucleic acid structures that fold from guanine (G)–rich DNA and RNA strands. This field of research gains traction as a major chemical biology area since it aims at uncovering many key cellular mechanisms in which quadruplexes are involved. The wealth of knowledge acquired over the past three decades strongly supports pivotal roles of G4 in the regulation of gene expression at both transcriptional (DNA quadruplexes) and translational levels (RNA quadruplexes). Recent biochemical discoveries uncovered myriad of additional G4 actions: from chromosomal stability to the firing of replication origins, from telomere homeostasis to functional dysregulations underlying genetic diseases (including cancers and neurodegeneration). Here, we listed a repertoire of protocols that we have developed over the past years to visualize quadruplexes in cells. These achievements were made possible thanks to the discovery of a novel family of versatile quadruplex‐selective fluorophores, the twice‐as‐smart quadruplex ligands named TASQ (for template‐assembled synthetic G‐quartet). The versatility of this probe allows for multiple imaging techniques in both fixed and live cells, including the use of the multiphoton microscopy, confocal microscopy, and real‐time fluorescent image collection. © 2017 by John Wiley & Sons, Inc.