bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asymmetric Synthesis of Functionalized Tetrahydronaphthalenes via an Organocatalytic Nitroalkane‐Michael/Henry Domino Reaction
Authors: Enders Dieter , Hahn Robert , Atodiresei Iuliana 
Published: April 2013

AbstractAn organocatalytic nitroalkane‐Michael/Henry reaction sequence to functionalized 1,2,3,4‐tetrahydronaphthalen‐1‐ols is described. Starting from 2‐(nitromethyl)benzaldehyde and nitroalkenes a bifunctional quinine‐based squaramide organocatalyst is used to afford the title compounds in moderate to very good yields (25–84%), high diastereomeric ratios (dr>95:5) after crystallization and good to excellent enantioselectivities of 63–99% ee. Starting from γ‐nitro aldehydes and ketones secondary and tertiary cyclohexanols bearing four stereogenic centers can also be prepared with this Michael/Henry domino reaction.
Controlling enzyme inhibition using an expanded set of genetically encoded amino acids
Authors: Zheng Shun , Kwon Inchan 
Published: April 2013

ABSTRACTEnzyme inhibition plays an important role in drug development, metabolic pathway regulation, and biocatalysis with product inhibition. When an inhibitor has high structural similarities to the substrate of an enzyme, controlling inhibitor binding without affecting enzyme substrate binding is often challenging and requires fine‐tuning of the active site. We hypothesize that an extended set of genetically encoded amino acids can be used to design an enzyme active site that reduces enzyme inhibitor binding without compromising substrate binding. As a model case, we chose murine dihydrofolate reductase (mDHFR), substrate dihydrofolate, and inhibitor methotrexate. Structural models of mDHFR variants containing non‐natural amino acids complexed with each ligand were constructed to identify a key residue for inhibitor binding and non‐natural amino acids to replace the key residue. Then, we discovered that replacing the key phenylalanine residue with two phenylalanine analogs (p‐bromophenylalanine (pBrF) and L‐2‐naphthylalanine (2Nal)) enhances binding affinity toward the substrate dihydrofolate over the inhibitor by 4.0 and 5.8‐fold, respectively. Such an enhanced selectivity is mainly due to a reduced inhibitor binding affinity by 2.1 and 4.3‐fold, respectively. The catalytic efficiency of the mDHFR variant containing pBrF is comparable to that of wild‐type mDHFR, whereas the mDHFR variant containing 2Nal exhibits a moderate decrease in the catalytic efficiency. The work described here clearly demonstrates the feasibility of selectively controlling enzyme inhibition using an expanded set of genetically encoded amino acids. Biotechnol. Bioeng. 2013; 110:2361–2370. © 2013 Wiley Periodicals, Inc.
Bioreactor engineering using disposable technology for enhanced production of hCTLA4Ig in transgenic rice cell cultures
Authors: Kwon Jun‐Young , Yang Yong‐Suk , Cheon Su‐Hwan , Nam Hyung‐Jin , Jin Gi‐Hong , Kim Dong‐Il 
Published: April 2013

ABSTRACTTwo kinds of disposable bioreactors, air‐lift disposable bioreactors (ADB) and wave disposable bioreactors (WDB) were compared with stirred‐tank reactors (5‐L STR). These bioreactors were successfully applied to transgenic rice cell cultures for the production of recombinant human cytotoxic T‐lymphocyte antigen 4‐immunoglobulin (hCTLA4Ig). In both systems, a fed‐batch culture method was used to produce hCTLA4Ig efficiently by feeding concentrated amino acids and production levels were enhanced when dissolved oxygen (DO) level was regulated at 30% using pure oxygen sparging. Agitation and aeration rate during cultivation in ADB and WDB were determined by the same mixing time. The results in both disposable bioreactors showed similar values in maximum cell density (11.9 gDCW/L and 12.6 gDCW/L), doubling time (4.8‐ and 5.0‐day), and maximum hCTLA4Ig concentration (43.7 and 43.3 mg/L). Relatively higher cell viability was sustained in the ADB whereas hCTLA4Ig productivity was 1.2‐fold higher than that in WDB. The productivity was improved by increasing aeration rate (0.2 vvm). Overall, our experiments demonstrate pneumatically driven disposable bioreactors are applicable for the production of recombinant proteins in plant cell cultures. These results will be useful for development and scale‐up studies of disposable bioreactor systems for transgenic plant cell cultures. Biotechnol. Bioeng. 2013; 110:2412–2424. © 2013 Wiley Periodicals, Inc.
Investigating contactless high frequency ultrasound microbeam stimulation for determination of invasion potential of breast cancer cells
Authors: Hwang Jae Youn , Lee Nan Sook , Lee Changyang , Lam Kwok Ho , Kim Hyung Ham , Woo Jonghye , Lin Ming‐Yi , Kisler Kassandra , Choi Hojong , Zhou Qifa , Chow Robert H. , Shung K. Kirk 
Published: April 2013

ABSTRACTIn this article, we investigate the application of contactless high frequency ultrasound microbeam stimulation (HFUMS) for determining the invasion potential of breast cancer cells. In breast cancer patients, the finding of tumor metastasis significantly worsens the clinical prognosis. Thus, early determination of the potential of a tumor for invasion and metastasis would significantly impact decisions about aggressiveness of cancer treatment. Recent work suggests that invasive breast cancer cells (MDA‐MB‐231), but not weakly invasive breast cancer cells (MCF‐7, SKBR3, and BT‐474), display a number of neuronal characteristics, including expression of voltage‐gated sodium channels. Since sodium channels are often co‐expressed with calcium channels, this prompted us to test whether single‐cell stimulation by a highly focused ultrasound microbeam would trigger Ca2+ elevation, especially in highly invasive breast cancer cells. To calibrate the diameter of the microbeam ultrasound produced by a 200‐MHz single element LiNbO3 transducer, we focused the beam on a wire target and performed a pulse‐echo test. The width of the beam was ∼17 µm, appropriate for single cell stimulation. Membrane‐permeant fluorescent Ca2+ indicators were utilized to monitor Ca2+ changes in the cells due to HFUMS. The cell response index (CRI), which is a composite parameter reflecting both Ca2+ elevation and the fraction of responding cells elicited by HFUMS, was much greater in highly invasive breast cancer cells than in the weakly invasive breast cancer cells. The CRI of MDA‐MB‐231 cells depended on peak‐to‐peak amplitude of the voltage driving the transducer. These results suggest that HFUMS may serve as a novel tool to determine the invasion potential of breast cancer cells, and with further refinement may offer a rapid test for invasiveness of tumor biopsies in situ. Biotechnol. Bioeng. 2013;110: 2697–2705. © 2013 Wiley Periodicals, Inc.
Industrial symbiosis: Corn ethanol fermentation, hydrothermal carbonization, and anaerobic digestion
Authors: Wood Brandon M. , Jader Lindsey R. , Schendel Frederick J. , Hahn Nicholas J. , Valentas Kenneth J. , McNamara Patrick J. , Novak Paige M. , Heilmann Steven M. 
Published: April 2013

ABSTRACTThe production of dry‐grind corn ethanol results in the generation of intermediate products, thin and whole stillage, which require energy‐intensive downstream processing for conversion into commercial animal feed products. Hydrothermal carbonization of thin and whole stillage coupled with anaerobic digestion was investigated as alternative processing methods that could benefit the industry. By substantially eliminating evaporation of water, reductions in downstream energy consumption from 65% to 73% were achieved while generating hydrochar, fatty acids, treated process water, and biogas co‐products providing new opportunities for the industry. Processing whole stillage in this manner produced the four co‐products, eliminated centrifugation and evaporation, and substantially reduced drying. With thin stillage, all four co‐products were again produced, as well as a high quality animal feed. Anaerobic digestion of the aqueous product stream from the hydrothermal carbonization of thin stillage reduced chemical oxygen demand (COD) by more than 90% and converted 83% of the initial COD to methane. Internal use of this biogas could entirely fuel the HTC process and reduce overall natural gas usage. Biotechnol. Bioeng. 2013;110: 2624–2632. © 2013 Wiley Periodicals, Inc.
Long‐term adaptation of Saccharomyces cerevisiae to the burden of recombinant insulin production
Authors: Kazemi Seresht Ali , Cruz Ana Luisa , de Hulster Erik , Hebly Marit , Palmqvist Eva Akke , van Gulik Walter , Daran Jean‐Marc , Pronk Jack , Olsson Lisbeth 
Published: April 2013

ABSTRACTHigh‐level production of heterologous proteins is likely to impose a metabolic burden on the host cell and can thus affect various aspects of cellular physiology. A data‐driven approach was applied to study the secretory production of a human insulin analog precursor (IAP) in Saccharomyces cerevisiae during prolonged cultivation (80 generations) in glucose‐limited aerobic chemostat cultures. Physiological characterization of the recombinant cells involved a comparison with cultures of a congenic reference strain that did not produce IAP, and time‐course analysis of both strains aimed at identifying the metabolic adaptation of the cells towards the burden of IAP production. All cultures were examined at high cell density conditions (30 g/L dry weight) to increase the industrial relevance of the results. The burden of heterologous protein production in the recombinant strain was explored by global transcriptome analysis and targeted metabolome analysis, including the analysis of intracellular amino acid pools, glycolytic metabolites, and TCA intermediates. The cellular re‐arrangements towards IAP production were categorized in direct responses, for example, enhanced metabolism of amino acids as precursors for the formation of IAP, as well as indirect responses, for example, changes in the central carbon metabolism. As part of the long‐term adaptation, a metabolic re‐modeling of the IAP‐expressing strain was observed, indicating an augmented negative selection pressure on glycolytic overcapacity, and the emergence of mitochondrial dysfunction. The evoked metabolic re‐modeling of the cells led to less optimal conditions with respect to the expression and processing of the target protein and thus decreased the cellular expression capacity for the secretory production of IAP during prolonged cultivation. Biotechnol. Bioeng. 2013;110: 2749–2763. © 2013 Wiley Periodicals, Inc.
Microwave‐Assisted Ethanol Reduction as a New Method for the Preparation of Highly Active and Stable CNT‐Supported PtRu Electrocatalysts for Methanol Oxidation
Authors: Nassr Abu Bakr Ahmed Amine , Bron Michael 
Published: April 2013

AbstractHighly active and stable PtRu nanocatalysts supported on carbon nanotubes were prepared by microwave‐assisted ethanol reduction in an ethanol/water mixture (1:1 v/v). During the reduction process, the presence of water is necessary for fast and substantial metal ion reduction. The prepared catalysts were characterized with inductively coupled plasma (ICP‐ES), TEM, XRD, and electrochemical techniques to investigate their structural properties and electrocatalytic activities. ICP analysis confirms the presence of Pt and Ru in the catalysts, whereas XRD and TEM analyses demonstrate the formation of nanoparticles in the Pt face‐centered‐cubic structure that have a narrow size distribution and are well dispersed on carbon nanotubes. Metal loading and Pt/Ru ratio are closer to the nominal values for catalysts prepared through microwave‐assisted ethanol reduction than those for catalysts prepared by conventional ethanol reduction. Heat treatment at different temperatures from 200 to 800 °C in a reductive atmosphere has a beneficial effect on the electrocatalytic activity of the catalysts and their stabilities under electrochemical conditions. A heat treatment temperature of 600 °C was found to be optimum for the activity and stability of the catalysts and tolerance for CO poisoning, which is discussed in view of the structural properties of the nanocatalysts and the higher degree of alloying. Temperatures higher than 600 °C led to the aggregation of nanocatalysts and formation of larger particles.
A Ruthenium Catalyst with Simple Triphenylphosphane for the Enantioselective Hydrogenation of Aromatic Ketones
Authors: Zhou Han , Huang Hanmin 
Published: April 2013

AbstractAn efficient Ru catalyst constructed from simple and commercially available triphenylphosphane and enantiopure (1S,1′S)‐1,1′‐biisoindoline (BIDN) was applied to the asymmetric hydrogenation of aromatic ketones. A range of simple aromatic ketones could be hydrogenated with good to excellent enantioselectivities (up to 95 % ee). An appropriate enantioselective transition state was proposed to explain the high enantioselectivity obtained with this catalytic system. This study represents the first example to establish a practical Noyori‐type catalyst with a simple achiral monophosphane for highly enantioselective hydrogenation.
Temperature‐Responsive Mixed‐Shell Polymeric Micelles for the Refolding of Thermally Denatured Proteins
Authors: Liu Xue , Liu Yang , Zhang Zhenkun , Huang Fan , Tao Qian , Ma Rujiang , An Yingli , Shi Linqi 
Published: April 2013

AbstractWe have fabricated a mixed‐shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroELGroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co‐assembly of block copolymers poly(lactide‐b‐poly(ethylene oxide) (PLA‐b‐PEG) and poly(lactide)‐b‐poly(N‐isopropylacryamide) (PLA‐b‐PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core–shell–corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone‐like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydrase B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more‐complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM‐based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases.
Incremental Predictive Value of Red Cell Distribution Width for 12‐Month Clinical Outcome After Acute Myocardial Infarction
Authors: Lee Jang Hoon , Yang Dong Heon , Jang Se Yong , Choi Won Suk , Kim Kyun Hee , Lee Won Kee , Bae Myung Hwan , Park Hun Sik , Cho Yongkeun , Chae Shung Chull 
Published: April 2013

AbstractBackgroundThe incremental predictive value of red cell distribution width (RDW) for major adverse cardiac events (MACEs) has not been fully investigated in patients with acute myocardial infarction (AMI).HypothesisThe aim of this study was to determine the incremental value of RDW to the established risk factors in predicting clinical outcomes after AMI.MethodsBetween November 2005 and January 2010, 1596 patients with AMI (1070 male; mean age, 64.5 ± 11.9 years) were analyzed in this study. Baseline levels of RDW were measured at the time of admission. The 12‐month MACEs were defined as death and nonfatal MI.ResultsThe RDW levels were significantly higher in patients with 12‐month MACEs (13.8 ± 1.3% vs 13.3 ± 1.2%, P < 0.001). In a Cox proportional hazards model, RDW (hazard ratio [HR]: 1.19, P = 0.016) was an independent predictor for 12‐month MACEs. Adding RDW to established risk factors and hemoglobin levels significantly improved prediction for 12‐month MACEs, as shown by the net reclassification improvement (0.297; P = 0.012) and integrated discrimination improvement (0.0143; P = 0.042). The likelihood ratio test showed that RDW added incremental predictive value to the combination of hemoglobin and established risk factors (P = 0.005). Patients were categorized into 4 groups according to quartiles of RDW at baseline. Adjusted HRs for 12‐month MACEs were 1 (RDW ≤12.6%, reference), 4.24 (RDW 12.7%–13.1%, P = 0.01), 4.36 (RDW 13.2%–13.9%, P = 0.008), and 6.18 (RDW 13.2%–13.9%, P = 0.001), respectively.ConclusionsIn post‐myocardial infarction patients, baseline RDW levels at admission could provide incremental predictive value to established risk factors for predicting 12‐month MACEs.
Small‐Molecule Regulators of Autophagy and Their Potential Therapeutic Applications
Authors: Zhou Mi , Wang Renxiao 
Published: April 2013

AbstractAutophagy is a highly conserved process in which damaged proteins and organelles are sequestered in double‐membrane autophagosomes and delivered to lysosomes for degradation and recycling. As an efficient response to cellular stress, autophagy is essential for the maintenance of cellular homeostasis. Defective autophagy is associated with a variety of diseases, including cancer. This article summarizes current knowledge about the molecular mechanism of autophagy and its role in tumorigenesis. Particular focus is placed on the development of small‐molecule regulators of autophagy and their potential application as anticancer therapeutic agents.
Markov Chain Approximations to Nonsymmetric Diffusions with Bounded Coefficients
Authors: Deuschel Jean‐Dominique , Kumagai Takashi 
Published: April 2013

AbstractWe consider a certain class of nonsymmetric Markov chains and obtain heat kernel bounds and parabolic Harnack inequalities. Using the heat kernel estimates, we establish a sufficient condition for the family of Markov chains to converge to nonsymmetric diffusions. As an application, we approximate nonsymmetric diffusions in divergence form with bounded coefficients by nonsymmetric Markov chains. This extends the results by Stroock and Zheng to the nonsymmetric divergence forms. © 2012 Wiley Periodicals, Inc.
On an Isoperimetric Problem with a Competing Nonlocal Term I: The Planar Case
Authors: Knüpfer Hans , Muratov Cyrill B. 
Published: April 2013

AbstractThis paper is concerned with a study of the classical isoperimetric problem modified by an addition of a nonlocal repulsive term. We characterize existence, nonexistence, and radial symmetry of the minimizers as a function of mass in the situation where the nonlocal term is generated by a kernel given by an inverse power of the distance. We prove that minimizers of this problem exist for sufficiently small masses and are given by disks with prescribed mass below a certain threshold when the interfacial term in the energy is dominant. At the same time, we prove that minimizers fail to exist for sufficiently large masses due to the tendency of the low‐energy configuration to split into smaller pieces when the nonlocal term in the energy is dominant. In the latter regime, we also establish linear scaling of energy with mass, suggesting that for large masses low‐energy configurations consist of many roughly equal‐size pieces far apart. In the case of slowly decaying kernels, we give a complete characterization of the minimizers. © 2012 Wiley Periodicals, Inc.
Provably secure certificate‐based key‐insulated signature scheme
Authors: Li Jiguo , Du Haiting , Zhang Yichen , Li Tao , Zhang Yuexin 
Published: April 2013

SUMMARYCertificate‐based signature computation is often performed on insecure devices where the signature key is easy to be exposed. To reduce the influence of key exposure, we introduce key‐insulated mechanism into certificate‐based cryptography and formalize the notion and security model of the certificate‐based key‐insulated signature scheme. We then present a certificate‐based key‐insulated signature scheme, which is proven to be existentially unforgeable against adaptive chosen message attacks in the random oracle model. The proposed scheme has potential applications in trusted computing. Copyright © 2013 John Wiley & Sons, Ltd.
Enhanced Li Adsorption and Diffusion in Single‐Walled Silicon Nanotubes: An ab Initio Study
Authors: Kulish Vadym V. , Ng Man‐Fai , Malyi Oleksandr I. , Wu Ping , Chen Zhong 
Published: April 2013

AbstractWe report a first‐principles investigation of Li adsorption and diffusion in single‐walled Si nanotubes (SWSiNTs) of interest to Li‐ion battery anodes. We calculate Li insertion characteristics in SWSiNTs and compare them with the respective ones in carbon nanotubes (CNTs) and other silicon nanostructures. From our calculations, SWSiNTs show higher reactivity toward the adsorption of Li adatoms than CNTs and Si nanoclusters. Considering the importance of Li kinetics, we demonstrate that the interior of SWSiNTs may serve as a fast Li diffusion channel. The important advantage of SWSiNTs over their carbon analogues is a sevenfold reduction in the energy barrier for the penetration of the Li atoms into the nanotube interior through the sidewalls. This prepossesses easier Li diffusion inside the tube and subsequent utilization of the interior sites, which enhances Li storage capacity of the system. The improvements in both Li uptake and Li mobility over their analogues support the great potential of SWSiNTs as Li‐ion battery anodes.
Optimization of a Membraneless Glucose/Oxygen Enzymatic Fuel Cell Based on a Bioanode with High Coulombic Efficiency and Current Density
Authors: Shao Minling , Zafar Muhammad Nadeem , Falk Magnus , Ludwig Roland , Sygmund Christoph , Peterbauer Clemens K. , Guschin Dmitrii A. , MacAodha Domhnall , Ó Conghaile Peter , Leech Dónal , Toscano Miguel D. , Shleev Sergey , Schuhmann Wolfgang , Gorton Lo 
Published: April 2013

AbstractAfter initial testing and optimization of anode biocatalysts, a membraneless glucose/oxygen enzymatic biofuel cell possessing high coulombic efficiency and power output was fabricated and characterized. Two sugar oxidizing enzymes, namely, pyranose dehydrogenase from Agaricus meleagris (AmPDH) and flavodehydrogenase domains of various cellobiose dehydrogenases (DHCDH) were tested during the pre‐screening. The enzymes were mixed, “wired” and entrapped in a low‐potential Os‐complex‐modified redox‐polymer hydrogel immobilized on graphite. This anode was used in combination with a cathode based on bilirubin oxidase from Myrothecium verrucaria adsorbed on graphite. Optimization showed that the current density for the mixed enzyme electrode could be further improved by using a genetically engineered variant of the non‐glycosylated flavodehydrogenase domain of cellobiose dehydrogenase from Corynascus thermophilus expressed in E. coli (ngDHCtCDHC310Y) with a high glucose‐turnover rate in combination with an Os‐complex‐modified redox polymer with a high concentration of Os complexes as well as a low‐density graphite electrode. The optimized biofuel cell with the AmPDH/ngDHCtCDHC310Y anode showed not only a similar maximum voltage as with the biofuel cell based only on the ngDHCtCDHC310Y anode (0.55 V) but also a substantially improved maximum power output (20 μW cm−2) at 300 mV cell voltage in air‐saturated physiological buffer. Most importantly, the estimated half‐life of the mixed biofuel cell can reach up to 12 h, which is apparently longer than that of a biofuel cell in which the bioanode is based on only one single enzyme.