bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ion channel electrophysiology via integrated planar patch‐clamp chip with on‐demand drug exchange
Authors: Chen Chang‐Yu , Tu Ting‐Yuan , Jong De‐Shien , Wo Andrew M. 
Published: February 2011

AbstractPlanar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor‐specific measurement and allowing rapid replacement of the cell‐contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on‐demand. Volume‐regulated chloride channel and voltage‐gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch‐clamp system for ion channel assays. Biotechnol. Bioeng. 2011; 108:1395–1403. © 2011 Wiley Periodicals, Inc.
Construction of an E. Coli genome‐scale atom mapping model for MFA calculations
Authors: Ravikirthi Prabhasa , Suthers Patrick F. , Maranas Costas D. 
Published: February 2011

AbstractMetabolic flux analysis (MFA) has so far been restricted to lumped networks lacking many important pathways, partly due to the difficulty in automatically generating isotope mapping matrices for genome‐scale metabolic networks. Here we introduce a procedure that uses a compound matching algorithm based on the graph theoretical concept of pattern recognition along with relevant reaction information to automatically generate genome‐scale atom mappings which trace the path of atoms from reactants to products for every reaction. The procedure is applied to the iAF1260 metabolic reconstruction of Escherichia coli yielding the genome‐scale isotope mapping model imPR90068. This model maps 90,068 non‐hydrogen atoms that span all 2,077 reactions present in iAF1260 (previous largest mapping model included 238 reactions). The expanded scope of the isotope mapping model allows the complete tracking of labeled atoms through pathways such as cofactor and prosthetic group biosynthesis and histidine metabolism. An EMU representation of imPR90068 is also constructed and made available. Biotechnol. Bioeng. 2011; 108:1372–1382. © 2011 Wiley Periodicals, Inc.
Modulation of antibody galactosylation through feeding of uridine, manganese chloride, and galactose
Authors: Gramer Michael J. , Eckblad Jackie J. , Donahue Ruth , Brown Joseph , Shultz Carrie , Vickerman Kent , Priem Patrick , van den Bremer Ewald T.J. , Gerritsen Jolanda , van Berkel Patrick H.C. 
Published: February 2011

AbstractThrough process transfer and optimization for increased antibody production to 3 g/L for a GS‐CHO cell line, an undesirable drop in antibody Fc galactosylation was observed. Uridine (U), manganese chloride (M), and galactose (G), constituents involved in the intracellular galactosylation process, were evaluated in 2‐L bioreactors for their potential to specifically increase antibody galactosylation. These components were placed in the feed medium at proportionally increasing concentrations from 0 to 20× UMG, where a 1× concentration of U was 1 mM, a 1× concentration of M was 0.002 mM, and a 1× concentration of G was 5 mM. Antibody galactosylation increased rapidly from 3% at 0× UMG up to 21% at 8× UMG and then more slowly to 23% at 20× UMG. The increase was primarily due to a shift from G0F to G1F, with minimal impact on other glycoforms or product quality attributes. Cell culture performance was largely not impacted by addition of up to 20× UMG except for suppression of glucose consumption and lactate production at 16 and 20× UMG and a slight drop in antibody concentration at 20× UMG. Higher accumulation of free galactose in the medium was observed at 8× UMG and above, coincident with achieving the plateau of maximal galactosylation. A concentration of 4× UMG resulted in achieving the target of 18% galactosylation at 2‐L scale, a result that was reproduced in a 1,000‐L run. Follow‐up studies to evaluate the addition of each component individually up to 12× concentration revealed that the effect was synergistic; the combination of all three components gave a higher level of galactosylation than addition of the each effect independently. The approach was found generally useful since a second cell line responded similarly, with an increase in galactosylation from 5% to 29% from 0 to 8× UMG and no further increase or impact on culture performance up to 12× UMG. These results demonstrate a useful approach to provide exact and specific control of antibody galactosylation through manipulation of the concentrations of uridine, manganese chloride, and galactose in the cell culture medium. Biotechnol. Bioeng. 2011; 108:1591–1602. © 2011 Wiley Periodicals, Inc.
Induction of anthraquinone biosynthesis in Rubia cordifolia cells by heterologous expression of a calcium‐dependent protein kinase gene
Authors: Shkryl Y.N. , Veremeichik G.N. , Bulgakov V.P. , Zhuravlev Y.N. 
Published: February 2011

AbstractCalcium‐dependent protein kinases (CDPKs) play an important role in plant cell responses to stress and pathogenic attack. In this study, we investigated the effect of heterologous expression of the Arabidopsis CDPK gene, AtCPK1, on anthraquinone production in transgenic Rubia cordifolia cells. AtCPK1 variants (a constitutively active, Ca2+‐independent form and a non‐active form used as a negative control) were transferred to callus cells by agrobacterial transformation. Overexpression of the constitutively active, Ca2+‐independent form in R. cordifolia cells caused a 10‐fold increase in anthraquinone content compared with non‐transformed control cells, while the non‐active form of AtCPK1 had no effect on anthraquinone production. Real‐time PCR measurements showed that the activation of anthraquinone biosynthesis in transgenic calli correlated with the activation of isochorismate synthase gene expression. The activator effect of AtCPK1 was stable during prolonged periods of transgenic cell cultivation (more than 3 years) and the transgenic cultures exhibited high growth. Our results provide the first evidence that a CDPK gene can be used for the engineering of secondary metabolism in plant cells. Biotechnol. Bioeng. 2011; 108:1734–1738. © 2011 Wiley Periodicals, Inc.
IgLONs form heterodimeric complexes on forebrain neurons
Authors: McNamee Christine J. , Youssef Sahar , Moss Diana 
Published: February 2011

AbstractIgLONs are a family of four GPI‐anchored cell adhesion molecules that regulate neurite outgrowth and synaptogenesis and may act as tumour suppressor genes. Recently we have proposed that two members of the IgLON family act as a heterodimeric complex termed DIgLON. Neurons isolated from chick forebrain co‐express all six combinations of IgLONs and the intensity of fluorescence for each pair of IgLONs was highly correlated. Antibody‐patching experiments on forebrain neurons show complex formation for IgLON pairs but not between unrelated GPI‐anchored glycoproteins. Thus IgLONs are the first GPI‐anchored family of glycoproteins shown to form heterodimeric complexes in the plane of the membrane. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis and Pro‐Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives
Authors: Logashenko Evgeniya B. , Salomatina Oksana V. , Markov A. V. , Korchagina Dina V. , Salakhutdinov Nariman F. , Tolstikov Genrikh A. , Vlassov Valentin V. , Zenkova Marina A. 
Published: February 2011

AbstractTriterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti‐inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH‐glycyrrhetinic acid, the novel synthetic derivative methyl 2‐cyano‐3,12‐dioxo‐18βH‐olean‐9(11),1(2)‐dien‐30‐oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug‐resistance phenotype. It causes cell death by inducing the intrinsic caspase‐dependent apoptotic pathway.
Spacer Effects on in vivo Properties of DOTA‐Conjugated Dimeric [Tyr3]Octreotate Peptides Synthesized by a “CuI‐Click” and “Sulfo‐Click” Ligation Method
Authors: Yim Cheng‐Bin , van der Wildt Berend , Dijkgraaf Ingrid , Joosten Lieke , Eek Annemarie , Versluis Cees , Rijkers Dirk T. S. , Boerman Otto C. , Liskamp Rob M. J. 
Published: February 2011

AbstractWe report on the SSTR2‐binding properties of a series of four dimeric [Tyr3]octreotate analogues with different spacer lengths (nine, 19, 41, and 57 atoms) between the peptides. Two analogues (9 and 57 atoms) were selected as precursors for the design, synthesis, and biological evaluation of DOTA‐conjugated dimeric [Tyr3]octreotate analogues for tumor targeting. These compounds were synthesized by using a two‐stage click ligation procedure: a CuI‐catalyzed 1,3‐dipolar cycloaddition (“copper‐click” reaction) and a thio acid/sulfonyl azide amidation (“sulfo‐click” reaction). The IC50 values of these DOTA‐conjugated [Tyr3]octreotate analogues were comparable, and internalization studies showed that the nine‐atom 111In‐DOTA‐labeled [Tyr3]octreotate dimer had rapid and high receptor binding. Biodistribution studies with BALB/c nude mice bearing subcutaneous AR42J tumors showed that the 111In‐labeled [Tyr3]octreotate dimer (nine atoms) had a high tumor uptake at 1 h p.i. (38.8±8.3 % ID g−1), and excellent tumor retention at 4 h p.i. (40.9±2.5 % ID g−1). However, the introduction of the extended hydrophilic 57 atoms spacer led to rapid clearance from the circulation; this limited tumor accumulation of the radiotracer (21.4±4.9 % ID g−1 at 1 h p.i.). These findings provide important insight on dimerization and spacer effects on the in vivo properties of DOTA‐conjugated [Tyr3]octreotate dimers.
Catalytic Co‐Homologation of Alkanes and Dimethyl Ether and Promotion by Adamantane as a Hydride Transfer Co‐Catalyst
Authors: Simonetti Dante A. , Ahn John H. , Iglesia Enrique 
Published: February 2011

AbstractWe provide kinetic and isotopic evidence for the co‐homologation of linear and branched alkanes with dimethyl ether (DME) to form larger branched alkanes and isobutane on H‐BEA zeolites, and for the role of adamantane as a hydride transfer co‐catalyst that allows the activation of CH bonds in alkanes at low temperatures (<500 K) on Brønsted acid sites. Branched alkanes (isobutane, isopentane, and 2,3‐dimethylbutane) present in equimolar mixtures with DME form the corresponding alkenes via hydride transfer to bound alkoxides (formed in DME homologation steps) and subsequent deprotonation; these alkenes, derived from the added alkanes, are then methylated to lengthen their chain by using DME‐derived C1 species, as shown by the isotopologues formed in reactions of 13C‐DME with 12C‐alkanes. Linear alkanes are much less reactive than branched alkanes, because of their stronger CH bonds and larger carbenium ion formation energies, which determines hydride‐transfer rates to a given acceptor molecule. Adamantane increased the hydride‐transfer rates to bound alkoxides from branched alkanes, and even from unreactive linear alkanes, while also increasing their extent of incorporation into DME homologation pathways; adamantane acts as a reversible hydrogen donor that mediates dehydrogenation of alkanes at low temperatures on acid sites. The co‐homologation of alkanes with DME avoids the need for carbon rejection in the form of arenes to satisfy the hydrogen balance in the DME conversion to alkanes, provides a robust strategy for increasing the chain length and extent of branching in light alkanes through the selective addition of C1 species, and mitigates the formation of unsaturated by‐products ubiquitous in the homologation of DME or methanol on Brønsted acids.
How Does Aromaticity Rule the Thermodynamic Stability of Hydroporphyrins?
Authors: Otero Nicolás , Fias Stijn , Radenković Slavko , Bultinck Patrick , Graña Ana M. , Mandado Marcos 
Published: February 2011

AbstractSeveral measures of aromaticity including energetic, magnetic, and electron density criteria are employed to show how aromatic stabilization can explain the stability sequence of hydroporphyrins, ranging from porphin to octahydroporphin, and their preferred hydrogenation paths. The methods employed involve topological resonance energies and their circuit energy effects, bond resonance energies, multicenter delocalization indices, ring current maps, magnetic susceptibilities, and nuclear‐independent chemical shifts. To compare the information obtained by the different methods, the results have been put in the same scale by using recently proposed approaches. It is found that all of them provide essentially the same information and lead to similar conclusions. Also, hydrogenation energies along different hydrogenation paths connecting porphin with octahydroporphin have been calculated with density functional theory. It is shown by using the methods mentioned above that the relative stability of different hydroporphyrin isomers and the observed inaccessibility of octahydroporphin both synthetically and in nature can be perfectly rationalized in terms of aromaticity.
Prospective study of growth and development in older girls and risk of benign breast disease in young women
Authors: Berkey Catherine S. , Willett Walter C. , Frazier A. Lindsay , Rosner Bernard , Tamimi Rulla M. , Colditz Graham A. 
Published: February 2011

AbstractBACKGROUND:In adult women with retrospective data, childhood adiposity, pubertal growth and development were associated with benign breast disease (BBD) and/or breast cancer. The authors prospectively evaluated these childhood/adolescent characteristics and BBD risk.METHODS:The Growing Up Today Study (GUTS) included females, aged 9‐15 years in 1996, who completed annual questionnaires through 2001, then 2003, 2005, and 2007. Participants annually/biennially provided information on menarche, height, and weight, from which the authors derived body mass index (BMI in kg/m2). Peak height growth velocity (PHV in cm/year) was estimated from longitudinal data. On 2005‐2007 surveys, 6899 females (18‐27 years of age) reported whether a healthcare provider ever diagnosed BBD (n = 147), and whether it was confirmed by biopsy (n = 67). Logistic models investigated risk factors adjusted for age, alcohol, pregnancy, and maternal history.RESULTS:More childhood adiposity (odds ratio [OR], 0.91/[kg/m2]; P = .04) and shorter adult height (OR, 0.93/inch shorter; P = .07) were associated with lower risk of biopsy‐confirmed BBD. Girls with most rapid height growth were at increased risk (OR, 2.12; P = .09) relative to those with the slowest growth. Age at menarche was not associated (OR, 1.11/year; P = .32) nor was adult BMI (adjusted for childhood BMI: OR, 1.01/[kg/m2]; P = .98); larger BMI increases (childhood to adulthood) were not protective (OR + 1.04/[kg/m2]; P = .37). Among girls with maternal breast cancer, those with more rapid growth had higher risk (OR, 1.47/[cm/year]; P = .02). All estimates were age‐adjusted.CONCLUSIONS:Increased BBD risk (likely evolving to elevated breast cancer risk) was observed in thinner girls, girls with the most rapid growth, and taller women. Contrary to expectations, later menarche age was not protective against BBD, consistent with studies that found BBD patients are not protected against breast cancer by later menarche. Cancer 2011. © 2011 American Cancer Society.
Using GI‐G‐1 queuing model for rtPS performance evaluation in 802.16 networks
Authors: Kao Shang‐Juh , Chuang Chia‐Chuan 
Published: February 2011

SUMMARYAmong the scheduling services, rtPS (real‐time polling service) is designated for real‐time applications. Among three packet delay intervals, performance effect on polling interval has been widely studied, but less on the intervals of scheduling and delivery. To evaluate the performance of delay‐sensitive rtPS applications, instead of using continuous queueing model, a discrete‐time GI‐G‐1 model, which considers intervals of polling, scheduling, and delivery, is proposed. By taking VoIP as a typical rtPS application, the transmission latency under different QoS settings, polling probability, and traffic load are presented. The latency is also compared among various codec schemes. The results indicate that when the codec rate is either fulfilled or dissatisfied by the promised bandwidth of service levels, the performance is highly dependent upon the polling probability, no matter what the traffic condition is. However, if the codec rate is in between the promised bandwidth of various service levels, the polling probability is a dominant factor in light traffic environment, while the settings on QoS parameters will strongly determine the performance in heavy traffic situation. In addition to the verification using simulation, the bandwidth utilization derived from the GI‐G‐1 model can be applied to improve the serving capacity of base stations. Copyright © 2011 John Wiley & Sons, Ltd.
Skype‐Hunter: A real‐time system for the detection and classification of Skype traffic
Authors: Adami Davide , Callegari Christian , Giordano Stefano , Pagano Michele , Pepe Teresa 
Published: February 2011

SUMMARYIn the previous years, Skype has gained more and more popularity, since it is seen as the best VoIP software with good quality of sound, ease of use and one that works everywhere and with every OS. Because of its great diffusion, both the operators and the users are, for different reasons, interested in detecting Skype traffic.In this paper we propose a real‐time algorithm (named Skype‐Hunter) to detect and classify Skype traffic. In more detail, this novel method, by means of both signature‐based and statistical procedures, is able to correctly reveal and classify the signaling traffic as well as the data traffic (calls and file transfers). To assess the effectiveness of the algorithm, experimental tests have been performed with several traffic data sets, collected in different network scenarios. Our system outperforms the ‘classical’ statistical traffic classifiers as well as the state‐of‐the‐art ad hoc Skype classifier. Copyright © 2011 John Wiley & Sons, Ltd.
Acute hypercapnic respiratory failure associated with hemodialysis
Authors: Palacios Carlos R. Franco , Altayeh Abdullah , Qian Qi 
Published: February 2011

AbstractPatients undergoing hemodialysis are subject to recurrent acid‐base perturbations. Prior to each dialysis treatment, they are relatively acidemic, which is corrected rapidly during dialysis. We report a patient with obesity, obstructive lung disease, and pneumonia who developed acute respiratory failure triggered by an inﬂux of high bicarbonate during dialysis. This case emphasizes that in patients with severely compromised respiratory reserve, a large amount of bicarbonate inﬂux during hemodialysis may cause acute CO2 accumulation and ventilatory distress. An individualized approach with judicious adjustment of the dialysate bicarbonate concentration may be necessary. Dial. Transplant. © 2011 Wiley Periodicals, Inc.
Taste bud cells of adult mice are responsive to Wnt/β‐catenin signaling: Implications for the renewal of mature taste cells
Authors: Gaillard Dany , Barlow Linda A. 
Published: February 2011

AbstractWnt/β‐catenin signaling initiates taste papilla development in mouse embryos, however, its involvement in taste cell turnover in adult mice has not been explored. Here we used the BATGAL reporter mouse model, which carries an engineered allele in which the LacZ gene is expressed in the presence of activated β‐catenin, to determine the responsiveness of adult taste bud cells to canonical Wnt signaling. Double immunostaining with markers of differentiated taste cells revealed that a subset of Type I, II, and III taste cells express β‐galactosidase. Using in situ hybridization, we showed that β‐catenin activates the transcription of the LacZ gene mainly in intragemmal basal cells that are immature taste cells, identified by their expression of Sonic Hedgehog (Shh). Finally, we showed that β‐catenin activity is significantly reduced in taste buds of 25‐week‐old mice compared with 10‐week‐old animals. Our data suggest that Wnt/β‐catenin signaling may influence taste cell turnover by regulating cell differentiation. Reduced canonical Wnt signaling in older mice could explain in part the loss of taste sensitivity with aging, implicating a possible deficiency in the rate of taste cell renewal. More investigations are now necessary to understand if and how Wnt signaling regulates adult taste cell turnover. genesis 49:295–306, 2011. © 2011 Wiley‐Liss, Inc.
Podosomal proteins as causes of human syndromes: A role in craniofacial development?
Authors: Cejudo‐Martin Pilar , Courtneidge Sara A. 
Published: February 2011

AbstractPodosomes and invadopodia are actin‐rich protrusions of the plasma membrane important for matrix degradation and cell migration. Most of the information in this field has been obtained in cancer cells, where the presence of invadopodia has been related to increased invasiveness and metastatic potential. The importance of the related podosome structure in other pathological or physiological processes that require cell invasion is relatively unexplored. Recent evidence indicates that essential components of podosomes are responsible for several human syndromes, some of which are characterized by serious developmental defects involving the craniofacial area, skeleton and heart, and very poor prognosis. Here we will review them and discuss the possible role of podosomes as a player in correct embryo development. genesis 49:209–221, 2011. © 2011 Wiley‐Liss, Inc.
Automatic Train Operation Using Autonomic Prediction of Train Runs
Authors: Asuka Masashi , Kataoka Kenji , Komaya Kiyotoshi , Nishida Syogo 
Published: February 2011

AbstractIn this paper, we present an automatic train control method adaptable to disturbed train traffic conditions. The proposed method presumes transmission of detected time of a home track clearance to trains approaching the station by employing equipment of Digital ATC (Automatic Train Control). Using the information, each train controls its acceleration by a method that consists of two approaches. First, by setting a designated restricted speed, the train controls its running time to arrive at the next station in accordance with predicted delay. Second, the train predicts the time at which it will reach the current braking profile generated by Digital ATC, along with the time when the braking profile transits ahead. By comparing them, the train correctly chooses the coasting drive mode in advance to avoid deceleration due to the current braking profile. We evaluated the effectiveness of the proposed method regarding driving conditions, energy consumption, and reduction of delays by simulation. © 2011 Wiley Periodicals, Inc. Electr Eng Jpn, 175(3): 65–73, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.10020/eej.21080