bluuebunny/crossref_metadata_2025_split huggingface dataset:
A fine‐tuned composition of protein nanofibrils yields an upgraded functionality of displayed antibody binding domains
Authors: Schmuck Benjamin , Sandgren Mats , Härd Torleif 
Published: April 2017

AbstractElevated performance of instruments and electronic devices is frequently attained through miniaturization of the involved components, which increases the number of functional units in a given volume. Analogously, to conquer the limitations of materials used for the purification of monoclonal antibodies and for the sensitivity of immunoassays, the support for capturing antibodies requires miniaturization. A suitable scaffold for this purpose are cross‐β structured protein nanofibrils, as they offer a superior surface area over volume ratio and because manipulation can be implemented genetically. To display the antibody binding Z‐domain dimers (ZZ) along the surface of the fibrils and grant maximal accessibility to the functional units, the N‐terminal fragments of the fibrillating translation release factor Sup35 or ureidosuccinate transporter Ure2, both from Saccharomyces cerevisae, are simultaneously fibrillated with the chimeric‐proteins Sup35‐ZZ and ZZ‐Ure2, respectively. Optimization of the fibril composition yields a binding capacity of 1.8 mg antibody per mg fibril, which is a binding capacity that is almost 20‐fold higher, compared to the commercially available affinity medium gold standard, protein A sepharose. This study lifts the craft of nanofibril functionalization to the next level, and offers a universal framework to improve biomaterials that rely on the display of functional proteins or enzymes.
Biocatalytic virus capsid as nanovehicle for enzymatic activation of Tamoxifen in tumor cells
Authors: Tapia‐Moreno Alejandro , Juarez‐Moreno Karla , Gonzalez‐Davis Oscar , Cadena‐Nava Ruben D. , Vazquez‐Duhalt Rafael 
Published: April 2017

AbstractMost of the drugs used in chemotherapy should be activated by a transformation catalyzed by cytochrome P450 (CYP) enzymes. In this work, bacteriophage P22 virus‐like particles (VLPs) containing CYP activity, immunologically inert and functionalized in order to be recognized by human cervix carcinoma cells and human breast adenocarcinoma cells were designed. The CYP was encapsulated inside the virus capsid obtained from the bacteriophage P22. CYP and coat protein were both heterologously expressed inE. coli. The VLPs with enzymatic activity were covered with polyethylene glycol that was functionalized in its distal end with folic acid in order to be recognized by folate receptors exhibited on tumor cells. The capacity of biocatalytic VLPs to be recognized and internalized into tumor cells is demonstrated. The VLP‐treated cells showed enhanced capacity for the transformation of the pro‐drug tamoxifen, which resulted in an increase of the cell sensitivity to this oncological drug. In this work, the potential use of biocatalytic VLPs vehicles as a delivery system of medical relevant enzymes is clearly demonstrated. In addition to cancer treatment, this technology also offers an interesting platform as nano‐bioreactors for intracellular delivery of enzymatic activity for other diseases originated by the lack of enzymatic activity.
A single‐step FACS sorting strategy in conjunction with fluorescent vital dye imaging efficiently assures clonality of biopharmaceutical production cell lines
Authors: Fieder Jürgen , Schulz Patrick , Gorr Ingo , Bradl Harald , Wenger Till 
Published: April 2017

AbstractThe development of biopharmaceutical production cell lines typically starts with generation of heterogeneous populations of cells, from which then single cell clones are established. Several regulatory guidelines require that production cell lines are clonal, and the actual demonstration of clonality has been increasingly demanded by regulatory authorities over the last years. Here, the authors describe the relative contribution of flow cytometry mediated deposition of single cells in multiwell plates and subsequent imaging to assurance of clonality in a state of the art approach to single cell generation. Within the flow cytometry step, two unit operations are evaluated separately, doublet discrimination during event selection for deposition and droplet deposition accuracy. The imaging procedure is evaluated for the accuracy of detection of non‐clonal populations. By employing mixing experiments of cell populations, the authors demonstrate that doublet discrimination is highly efficient, and that an appropriately set up flow cytometry system already can generate >99.5% true single cell clones. The efficiency of the described imaging process depends on several factors, reaching an optimal detection rate of non‐clonal wells of about 99.8%. Our results demonstrate that one well characterized cloning step generate biopharmaceutical production cell lines with a probability of clonality of >99.99%.
Non-technical skills of surgeons and anaesthetists in simulated operating theatre crises
Authors: Doumouras A G , Hamidi M , Lung K , Tarola C L , Tsao M W , Scott J W , Smink D S , Yule S 
Published: April 2017

Abstract

Background
Deficiencies in non-technical skills (NTS) have been increasingly implicated in avoidable operating theatre errors. Accordingly, this study sought to characterize the impact of surgeon and anaesthetist non-technical skills on time to crisis resolution in a simulated operating theatre.

Methods
Non-technical skills were assessed during 26 simulated crises (haemorrhage and airway emergency) performed by surgical teams. Teams consisted of surgeons, anaesthetists and nurses. Behaviour was assessed by four trained raters using the Non-Technical Skills for Surgeons (NOTSS) and Anaesthetists' Non-Technical Skills (ANTS) rating scales before and during the crisis phase of each scenario. The primary endpoint was time to crisis resolution; secondary endpoints included NTS scores before and during the crisis. A cross-classified linear mixed-effects model was used for the final analysis.

Results
Thirteen different surgical teams were assessed. Higher NTS ratings resulted in significantly faster crisis resolution. For anaesthetists, every 1-point increase in ANTS score was associated with a decrease of 53·50 (95 per cent c.i. 31·13 to 75·87) s in time to crisis resolution (P &lt; 0·001). Similarly, for surgeons, every 1-point increase in NOTSS score was associated with a decrease of 64·81 (26·01 to 103·60) s in time to crisis resolution in the haemorrhage scenario (P = 0·001); however, this did not apply to the difficult airway scenario. Non-technical skills scores were lower during the crisis phase of the scenarios than those measured before the crisis for both surgeons and anaesthetists.

Conclusion
A higher level of NTS of surgeons and anaesthetists led to quicker crisis resolution in a simulated operating theatre environment.
Enrichment of apoplastic fluid with therapeutic recombinant protein for efficient biofarming
Authors: Chatterjee Aparajita , Das Narayan C. , Raha Sumita , Maiti Indu B. , Shrestha Ankita , Khan Ahamed , Acharya Sefali , Dey Nrisingha 
Published: April 2017

ObjectiveFor efficient biofarming we attempted to enrich plant interstitial fluid (IF)/apoplastic fluid with targeted recombinant therapeutic protein. We employed a synthetic human Glucocerebrosidase (GCB), a model biopharmaceutical protein gene in this study.ResultsTwenty one Nicotiana varieties, species and hybrids were initially screened for individual IF recovery and based on the findings, we selected Nicotiana tabacum NN (S‐9‐6), Nicotiana tabacum nn (S‐9‐7) and Nicotiana benthamiana (S‐6‐6) as model plants for raising transgenic expressing GCB via Agrobacterium mediated transformation under the control of M24 promoter; GCB specific activity in each transgenic lines were analyzed and we observed higher concentration of recombinant GCB in IF of these transgenic lines (S‐9‐6, S‐9‐7, and S‐6‐6) in comparison to their concentration in crude leaf extracts.ConclusionRecovery of valuable therapeutics in plant IF as shown in the present study holds great promise for promoting plant based biofarming. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:726–736, 2017
A strategy to accelerate protein production from a pool of clones in Chinese hamster ovary cells for toxicology studies
Authors: Hu Zhilan , Hsu Wendy , Pynn Abby , Ng Domingos , Quicho Donna , Adem Yilma , Kwong Zephie , Mauger Brad , Joly John , Snedecor Bradley , Laird Michael W. , Andersen Dana C. , Shen Amy 
Published: April 2017

In the biopharmaceutical industry, a clonally derived cell line is typically used to generate material for investigational new drug (IND)‐enabling toxicology studies. The same cell line is then used to generate material for clinical studies. If a pool of clones can be used to produce material for IND‐enabling toxicology studies (Pool for Tox (PFT) strategy) during the time a lead clone is being selected for clinical material production, the toxicology studies can be accelerated significantly (approximately 4 months at Genentech), leading to a potential acceleration of 4 months for the IND submission. We explored the feasibility of the PFT strategy with three antibodies—mAb1, mAb2, and mAb3—at the 2 L scale. For each antibody, two lead cell lines were identified that generated material with similar product quality to the material generated from the associated pool. For two antibody molecules, mAb1 and mAb2, the material generated by the lead cell lines from 2 L bioreactors was tested in an accelerated stability study and was shown to have stability comparable to the material generated by the associated pool. Additionally, we used this approach for two antibody molecules, mAb4 and mAb5, at Tox and GMP production. The materials from the Tox batch at 400 L scale and three GMP batches at 2000 L scale have comparable product quality attributes for both molecules. Our results demonstrate the feasibility of using a pool of clonally derived cell lines to generate material of similar product quality and stability for use in IND‐enabling toxicology studies as was derived from the final production clone, which enabled significant acceleration of timelines into clinical development. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1449–1455, 2017
Microbial cell disruption for improving lipid recovery using pressurized CO2: Role of CO2 solubility in cell suspension, sugar broth, and spent media
Authors: Howlader Md Shamim , French William Todd , Shields‐Menard Sara A. , Amirsadeghi Marta , Green Magan , Rai Neeraj 
Published: April 2017

The study of in situ gas explosion to lyse the triglyceride‐rich cells involves the solubilization of gas (e.g., carbon dioxide, CO2) in lipid‐rich cells under pressure followed by a rapid decompression, which allows the gas inside the cell to rapidly expand and rupture the cell from inside out. The aim of this study was to perform the cell disruption using pressurized CO2 as well as to determine the solubility of CO2 in Rhodotorula glutinis cell suspension, sugar broth media, and spent media. Cell disruption of R. glutinis was performed at two pressures of 2,000 and 3,500 kPa, respectively, at 295.2 K, and it was found from both scanning electron microscopy (SEM) and plate count that a substantial amount of R. glutinis was disrupted due to the pressurized CO2. We also found a considerable portion of lipid present in the aqueous phase after the disruption at P = 3,500 kPa compared to control (no pressure) and P = 2,000 kPa, which implied that more intracellular lipid was released due to the pressurized CO2. Solubility of CO2 in R. glutinis cell suspension was found to be higher than the solubility of CO2 in both sugar broth media and spent media. Experimental solubility was correlated using the extended Henry's law, which showed a good agreement with the experimental data. Enthalpy and entropy of dissolution of CO2 were found to be −14.22 kJ mol−1 and 48.10 kJ mol−1 K−1, 9.64 kJ mol−1 and 32.52 kJ mol−1 K−1, and 7.50 kJ mol−1 and 25.22 kJ mol−1 K−1 in R. glutinis, spent media, and sugar broth media, respectively. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:737–748, 2017
Superbanone, A New 2‐Aryl‐3‐benzofuranone and Other Bioactive Constituents from the Tube Roots of Butea superba
Authors: Boonsombat Jutatip , Prachyawarakorn Vilailak , Pansanit Acharavadee , Mahidol Chulabhorn , Ruchirawat Somsak , Thongnest Sanit 
Published: April 2017

Phytochemical investigation from the tube roots of Butea superba, led to the isolation and identification of a new 2‐aryl‐3‐benzofuranone named superbanone (1), one benzoin, 2‐hydroxy‐1‐(2‐hydroxy‐4‐methoxyphenyl)‐2‐(4‐methoxyphenyl)ethanone (2), eight pterocarpans (3 – 10), and eleven isoflavonoids (11 – 21). Compound 2 was identified for the first time as a natural product. The structure of the isolated compounds was elucidated using spectroscopic methods, mainly 1D‐ and 2D‐NMR. The isolated compounds and their derivatives were evaluated for α‐glucosidase inhibitory and antimalarial activities. Compounds 3, 7, 8, and 11 showed promising α‐glucosidase inhibitory activity (IC50 = 13.71 ± 0.54, 23.54 ± 0.75, 28.83 ± 1.02, and 12.35 ± 0.36 μm, respectively). Compounds 3 and 11 were twofold less active than the standard drug acarbose (IC50 = 6.54 ± 0.04 μm). None of the tested compounds was found to be active against Plasmodium falciparum strain 94. On the basis of biological activity results, structure–activity relationships are discussed.
Chemical Synthesis and Evaluation of a Disialic Acid‐Containing Dextran Polymer as an Inhibitor for the Interaction between Siglec 7 and Its Ligand
Authors: Yamaguchi Sho , Yoshimura Atsushi , Yasuda Yu , Mori Airi , Tanaka Hiroshi , Takahashi Takashi , Kitajima Ken , Sato Chihiro 
Published: April 2017

AbstractA new sialic acid (Sia)‐containing glycopolymer—a fluorescent probe with high‐density disialic acid (diSia) on the surface of polysaccharide dextran (diSia‐Dex)—was synthesized as a key molecule to regulate the Sia recognition lectins, Siglecs, that are involved in the immune system. According to our original methods, diSia was synthesized by α‐selective sialylation, and a dextran template possessing terminal acetylenes and amino groups was prepared. A diSia and a fluorescent molecule were subsequently introduced to surface‐modified dextran by Hüisgen reaction and amidation, respectively. The modulatory activity of Siglec7 was evaluated by using synthetic probes. DiSia‐Dex showed high binding avidity toward Siglec7, with a KD value of 5.87×10−10 m, and a high inhibitory activity for the interaction between Siglec7 and a ligand (GD3), with a IC50 value of 1.0 nm. Notably, diSia‐Dex was able to release Siglec7 from the pre‐existing Siglec7–GD3 complex, possibly due to its unique properties of a slow dissociation rate and a high association rate. Together, these data show that diSia‐Dex can be widely applicable as a modulator of Siglec7 functions.
New Human CD22/Siglec‐2 Ligands with a Triazole Glycoside
Authors: Prescher Horst , Schweizer Astrid , Kuhfeldt Elena , Nitschke Lars , Brossmer Reinhard 
Published: April 2017

AbstractCD22 is a member of the Siglec family. Considerable attention has been drawn to the design and synthesis of new Siglec ligands to explore target biology and innovative therapies. In particular, CD22‐ligand‐targeted nanoparticles with therapeutic functions have proved successful in preclinical settings for blood cancers, autoimmune diseases, and tolerance induction. Here we report the design, synthesis and affinity evaluation of a new class of Siglec ligands: namely sialic acid derivatives with a triazole moiety replacing the natural glycoside oxygen atom. In addition, we describe important and surprising differences in binding to CD22 expressed at the cell surface for compounds with distinct valences. The new class of compounds might serve as a template for the design of ligands for other members of the Siglec family and next‐generation CD22‐ligand‐based targeted therapies.
The Lipids of the Early Endosomes: Making Multimodality Work
Authors: Arumugam Senthil , Kaur Amandeep 
Published: April 2017

AbstractEarly endosomes are dynamic intracellular compartments that fuse with incoming endocytic carrier vesicles and associated cargoes from the plasma membrane. It has been long known that the chemical structures of lipids confer striking properties and rich biochemistry on bilayers. Although the organisational principles of the plasma membrane are relatively better understood, understanding endosomal membranes has been challenging. It has become increasingly apparent that endosomal membranes, because of their lipid compositions and interactions, use distinct lipid chemistries. We discuss the biochemical and biophysical phenomena in play at the early endosomal membrane. We focus on cholesterol, phosphoinositides, and phosphatidylserine and their clear roles in endosome functions. We discuss the various principles and mechanisms underpinning how these lipids are implicated at the functional level in the working of endosomes, and we summarise early endosomes as a multimodal organelle employing distinct lipid‐specific mechanisms.
Sialylation Is Dispensable for Early Murine Embryonic Development in Vitro
Authors: Abeln Markus , Borst Kristina M. , Cajic Samanta , Thiesler Hauke , Kats Elina , Albers Iris , Kuhn Maike , Kaever Volkhard , Rapp Erdmann , Münster‐Kühnel Anja , Weinhold Birgit 
Published: April 2017

AbstractThe negatively charged nonulose sialic acid (Sia) is essential for murine development in vivo. In order to elucidate the impact of sialylation on differentiation processes in the absence of maternal influences, we generated mouse embryonic stem cell (mESC) lines that lack CMP‐Sia synthetase (CMAS) and thereby the ability to activate Sia to CMP‐Sia. Loss of CMAS activity resulted in an asialo cell surface accompanied by an increase in glycoconjugates with terminal galactosyl and oligo‐LacNAc residues, as well as intracellular accumulation of free Sia. Remarkably, these changes did not impact intracellular metabolites or the morphology and transcriptome of pluripotent mESC lines. Moreover, the capacity of Cmas−/− mESCs for undirected differentiation into embryoid bodies, germ layer formation and even the generation of beating cardiomyocytes provides first and conclusive evidence that pluripotency and differentiation of mESC in vitro can proceed in the absence of (poly)sialoglycans.
Complications caused by adenosine during catheter ablation of atrial fibrillation
Authors: Liang Jackson J. , Kumareswaran Ramanan , Hyman Matthew C. , Moore Roger A. , Lin David , Frankel David S. 
Published: April 2017

Key Clinical MessageAdenosine is increasingly used to assess for dormant conduction following pulmonary vein isolation during atrial fibrillation ablation. While the half‐life of adenosine is typically short and side effects transient, operators should be aware of more serious, lasting adverse reactions including anaphylaxis and bronchospasm.
Less Frustration, More Activity—Theoretical Insights into Frustrated Lewis Pairs for Hydrogenation Catalysis
Authors: Mane Manoj V. , Vanka Kumar 
Published: April 2017

AbstractThe field of frustrated Lewis pair (FLP) chemistry has seen rapid development in only a few years. FLPs have performed most spectacularly in hydrogenation catalysis: a wide variety of FLP‐based systems can catalyze the hydrogenation of a range of different substrates, including imines, enamines, ketones, alkynes, and alkenes. However, FLP‐based hydrogenation catalysts are yet to match the efficiency of their transition‐metal counterparts. The current investigation reveals an important aspect of FLPs that can be exploited to improve their efficiency, that is, the more sterically hindered the FLP catalyst is, the lower is its turnover frequency. Full quantum chemical calculations with DFT for a family of different, experimentally known hydrogenation FLP catalysts shows that superior FLP catalysts can be designed by reducing the frustration (by reducing the steric demand and acid/base strength) in the FLP. However, as lowering the steric demand without reduction in the frustration can result in unwanted side reactions, the design of the most efficient FLP catalysts depends on tuning the system so that both the steric demand and the frustration are reduced appropriately.
Copper–Porphyrin–Metal–Organic Frameworks as Oxidative Heterogeneous Catalysts
Authors: Castro Kelly A. D. F. , Figueira Flávio , Mendes Ricardo F. , Cavaleiro José A. S. , Neves Maria da Graça P. M. S. , Simões Mário M. Q. , Almeida Paz Filipe A. , Tomé João P. C. , Nakagaki Shirley 
Published: April 2017

AbstractThe synthesis and structural characterization of novel metal–organic‐framework‐type materials obtained from the reaction of 5,10,15,20‐tetrakis[2,3,5,6‐tetrafluoro‐4‐(4‐pyridylsulfanyl)phenyl]porphyrin (H2P1) and 5,10,15,20‐tetrakis(4‐pyridyl)porphyrin (H2P2) with copper(II) acetate is reported. The new material, CuP1S, shows higher heterogeneous catalytic activity than the homogeneous porphyrin–copper(II) complex CuP1 in the oxidation of catechol into ortho‐benzoquinone in the presence of air (O2) or H2O2 (30 %).
Identifying the Electrochemical Processes in LiFeSO4F Cathodes for Lithium Ion Batteries
Authors: Blidberg Andreas , Sobkowiak Adam , Tengstedt Carl , Valvo Mario , Gustafsson Torbjörn , Björefors Fredrik 
Published: April 2017

AbstractThe electrochemical performance of tavorite LiFeSO4F can be considerably improved by coating the material with a conducting polymer (poly(3,4‐ethylenedioxythiophene); PEDOT). Herein, the mechanisms behind the improved performance are studied systematically by careful electrochemical analysis. It is shown that the PEDOT coating improves the surface reaction kinetics for the Li‐ion insertion into LiFeSO4F. For such coated materials no kinetic limitations remain, and a transition from solid state to solution‐based diffusion control was observed at 0.6 mA cm−2 (circa C/2). Additionally, the quantity of PEDOT is optimized to balance the weight added by the polymer and the improved electrochemical function. Post mortem analysis shows excellent stability for the LiFeSO4F‐PEDOT composite, and maintaining the electronic wiring is the most important factor for stable electrochemical cycling of LiFeSO4F. The insights and the methodology used to determine the rate‐controlling steps are readily transferable to other ion‐insertion‐based electrodes, and the findings are important for the development of improved battery electrodes.
A Novel Electrophoretic Deposited Coordination Supramolecular Network Film for Detecting Phosphate and Biophosphate
Authors: Chu Tianshu , Zhang Feng , Wang Yi , Yang Yangyi , Ng Seik Weng 
Published: April 2017

AbstractA series of new lanthanide coordination supramolecular networks (CSNs) based on nalidixic acid (HNA) ligand were designed and synthesized. Their crystal structures were determined by single‐crystal XRD techniques. Thin films of these compounds were first successfully deposited on indium tin oxide (ITO) glass through one‐step electrophoretic deposition under mild conditions. The europium CSN film exhibits intense red emission and can act as a highly sensitive luminescent sensor for H2PO4− anions and adenosine triphosphate (ATP) in aqueous solution. The limits of detection of H2PO4− and ATP can achieve 0.68 and 1.9 μm respectively. The sensing mechanism was further explored through fluorescence and UV techniques. The fabricated sensor also showed excellent selectivity towards these phosphates in the presence of other coexisting ions (F−, Cl−, Br−, I−, SO4−, CO32−, NO3−, and AcO−) without interference. Moreover, we demonstrated the feasibility of using this sensor to detect ATP in bovine serum samples, suggesting the potential value of application in real biosystems.