bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of SHP‐1 phosphatase activity by monovalent and bivalent SH2 phosphopeptide ligands
Authors: Teichmann Kathleen , Kühl Toni , Könnig Ina , Wieligmann Karin , Zacharias Martin , Imhof Diana 
Published: September 2009

AbstractA sequence derived from the epithelial receptor tyrosine kinase Ros (pY2267) represents a high‐affinity binding partner for protein tyrosine phosphatase SHP‐1 and was recently used as lead structure to analyze the recognition requirements for the enzyme's N‐SH2 domain. Here, we focused on a set of peptides comprising C‐terminally extended linear and conformationally constrained side chain‐bridged cyclic N‐SH2 ligands based on the consensus sequence LxpYhxh(h/b)(h/b) (x = any amino acid, h = hydrophobic, and b = basic residue). Furthermore, the bivalent peptides described were designed to modulate the activity of SHP‐1 through binding to both, the N‐SH2 domain as well as an independent binding site on the surface of the catalytic domain (PTP domain). Consistent with previous experimental findings, surface plasmon resonance experiments revealed dissociation constants of most compounds in the low micromolar range. One peptide, EGLNpYc[KVD]MFPAPEEENH2, displayed favorable binding affinity, but reduced ability to stimulate SHP‐1. Docking experiments revealed that the binding of this ligand occurs in binding mode I, recently described to lead to an inhibited activation of SHP‐1. In summary, results presented in this study suggest that inhibitory N‐SH2 ligands of SHP‐1 may be obtained by designing bivalent compounds that associate with the N‐SH2 domain and simultaneously occupy a specific binding site on the PTP domain. © 2009 Wiley Periodicals, Inc. Biopolymers 93: 102–112, 2010.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Ultra scale‐down approaches for clarification of mammalian cell culture broths in disc‐stack centrifuges
Authors: Zaman Ferhana , Allan Corey M. , Ho Sa V. 
Published: September 2009

AbstractUltra‐scale down (USD) methodology developed by University College London for cell broth clarification with industrial centrifuges was applied to two common cell lines (NS0 and GS‐CHO) expressing various therapeutic monoclonal antibodies. A number of centrifuges at various scales were used with shear devices operating either by high speed rotation or flow‐through narrow channels. The USD methodology was found effective in accounting for both gravitational and shear effects on clarification performance with three continuous centrifuges at pilot and manufacturing scales. Different shear responses were observed with the two different cell lines and even with the same cell line expressing different products. Separate particle size analysis of the treated broths seems consistent with the shear results. Filterability of the centrifuged solutions was also evaluated to assess the utility of the USD approach for this part of the clarification operation. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Application of modeling and simulation tools for the evaluation of biocatalytic processes: A future perspective
Authors: Sin Gürkan , Woodley John M. , Gernaey Krist V. 
Published: September 2009

AbstractModeling and simulation techniques have for some time been an important feature of biocatalysis research, often applied as a complement to experimental studies. In this short review, we report on the state‐of‐the‐art process and kinetic modeling for biocatalysis with the aim of identifying future research needs. We have particularly focused on four aspects of modeling: (i) the model purpose, (ii) the process model boundary, (iii) the model structure, and (iv) the model identification procedure. First, one finds that most of the existing models describe biocatalyst behavior in terms of enzyme selectivity, mechanism, and reaction kinetics. More recently, work has focused on extending these models to obtain process flowsheet descriptions. Second, biocatalysis models remain at a relatively low level of complexity compared with the trends observed in other engineering disciplines. Hence, there is certainly room for additional development, i.e., detailed mixing and hydrodynamics, more process units (e.g., biorefinery). Third, biocatalysis models have been only partially subjected to formal statistical analysis. In particular, uncertainty analysis is needed to ascertain reliability of the predictions of the process model, which is necessary to make sound engineering decisions (e.g., the optimal process flowsheet, control strategy, etc). In summary, for modeling studies to be more mature and successful, one needs to introduce Good Modeling Practice and that asks for (i) a standardized and systematic guideline for model development, (ii) formal identifiability analysis, and (iii) uncertainty analysis. This will advance the utility of models in biocatalysis for more rigorous application within process design, optimization, and control strategy evaluation. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Development of an animal‐component free medium for vero cells culture
Authors: Rourou Samia , van der Ark Arno , van der Velden Tiny , Kallel Héla 
Published: September 2009

AbstractThis work describes the development of an animal‐component free medium (IPT‐AFM) that allows an optimal growth of Vero cells, an adherent cell line used for the production of viral vaccines. Statistical experimental design was applied to identify crucial nutrients that affect cell growth. Using Medium 199 or MEM as a basal medium, a serum‐free medium (SFM) referred as IPT‐SFM that only enclosed transferrin as a component of animal origin was developed at first. Then, the composition of IPT‐SFM was further improved to obtain an animal‐component free medium named IPT‐AFM. IPT‐AFM contains M199 as a basal medium, plant hydrolysates, epidermal growth factor, ethanolamine, ferric citrate, and vitamin C. Among various plant hydrolysates, specific combinations of soy (Hypep 1510) and wheat gluten (Hypeps 4601 and 4605) hydrolysates, were identified to promote cell growth; whereas individual Hypeps had a minor positive effect on cell growth. Nevertheless, the removal of serum did influence cell attachment. Coating tissue‐culture flasks with teleostean, a product extracted from cold water fish skin, had not only enhanced cell attachment but also improved cell growth performance in static cultures. Different non‐animal proteases were also assessed as an alternative to trypsin. TrypLE Select, a recombinant trypsin, gave the best cell growth performances. Kinetics of cell growth in IPT‐AFM were investigated in T‐flasks, cell growth was comparable with that obtained in MEM+10% fetal calf serum (FCS). A mean cell division number equal to 2.26 ± 0.18 and a specific growth rate μ 0.019 ± 0.003 h−1 were achieved in IPT‐AFM. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Experimental and Theoretical Studies on Some Energetic Functionalized Trimethylamine Derivatives
Authors: Klapötke Thomas M. , Krumm Burkhard , Scherr Matthias , Steemann F. Xaver , Banert Klaus , Joo Young‐Hyuk 
Published: September 2009

AbstractThe synthesis and structural properties (from X‐ray diffraction or B3LYP/6‐31G(d) calculations) of three energetic compounds derived from tris(chloromethyl)amine and of tris(chloromethyl)amine itself were investigated and compared to those of compounds with similar structures. The compounds have almost planar NC3 units at their amine center, and the substituents bound to the CH2 groups tend to be reactive towards further substitution. Multiple hyperconjugation was used to explain these observations.
Minor Enantiomer Recycling: Metal Catalyst, Organocatalyst and Biocatalyst Working in Concert
Authors: Wingstrand Erica , Laurell Anna , Fransson Linda , Hult Karl , Moberg Christina 
Published: September 2009

AbstractA minor enantiomer recycling one‐pot procedure employing two reinforcing chiral catalysts has been developed. Continuous regeneration of the achiral starting material is effected via selective enzyme‐catalyzed hydrolysis of the minor product enantiomer from Lewis acid–Lewis base catalyzed addition of acyl cyanides to prochiral aldehydes in a two‐phase solvent system. The process provides O‐acylated cyanohydrins in close to perfect enantioselectivities, higher than those obtained in the direct process, and in high yields. A combination of a (S,S)‐salen Ti Lewis acid and Candida antarctica lipase B provides the products with R absolute configuration, whereas the opposite enantiomer is obtained from the (R,R)‐salen Ti complex and Candida rugosa lipase.
Discovery of New Natural Products by Intact‐Cell Mass Spectrometry and LC‐SPE‐NMR: Malbranpyrroles, Novel Polyketides from Thermophilic Fungus Malbranchea sulfurea
Authors: Yang Yu‐Liang , Liao Wen‐Ying , Liu Wan‐Yun , Liaw Chih‐Chuang , Shen Chia‐Ning , Huang Zih‐You , Wu Shih‐Hsiung 
Published: September 2009

AbstractSix photosensitive polyketides, malbranpyrroles A–F, were discovered from the thermophilic fungus Malbranchea sulfurea by using intact‐cell desorption/ionization on silicon mass (ICD‐MS) and LC‐SPE‐NMR. These two strategies facilitate the searching and structural determination of unstable natural products. The ICD‐MS indicated that only brown hyphae of M. sulfurea can produce malbranpyrroles. The biosynthetic pathway of malbranpyrroles was evidenced by 13C isotope precursors and amino acid feeding experiments. The cytotoxicity data revealed that the conformation of the conjugated system in malbranpyrroles does not affect cytotoxic potency against cancer cell lines. In addition, the chlorine atom was shown to be the pharmacophore for cytotoxicity.
A Simple Protocol to Stabilize Gold Nanoparticles using Amphiphilic Block Copolymers: Stability Studies and Viable Cellular Uptake
Authors: Rahme Kamil , Vicendo Patricia , Ayela Cédric , Gaillard Cédric , Payré Bruno , Mingotaud Christophe , Gauffre Fabienne 
Published: September 2009

AbstractDi‐ and triblock non‐ionic copolymers based on poly(ethylene oxide) and poly(propylene oxide) were studied for the stabilization of nanoparticles in water at high ionic strength. The effect of the molecular architecture (di‐ vs. triblock) of these amphiphilic copolymers was investigated by using gold nanoparticles (AuNPs) as probes for colloidal stability. The results demonstrate that both di‐ and triblock copolymers can provide long term stability, and that in both cases AuNPs are individually embedded within globules of polymers. However, in the case of diblock copolymers, the colloidal stability was related to the formation of micelles, in contrast with the case of triblock copolymers, which were previously shown to provide good stability even at concentrations at which micelles do not form. Quartz crystal microbalance (QCM) experiments showed that the presence of the hydrophobic block in the structure of the polymer is important to ensure quantitative adsorption upon a gold surface and to limit desorption. We demonstrate that with an appropriate choice of polymer, the polymer/AuNP hybrids can also undergo filtration and freeze‐drying without noticeable aggregation, which can be very convenient for further applications. Finally, preliminary studies of the cytotoxicity effect on fibroblast cells show that the polymer/AuNP hybrids were not cytotoxic. TEM micrographs on ultrathin sections of cells after incubation with the colloidal solutions show that the nanoparticles were internalized into the cells, conserving their initial size and shape.
Least squares estimation of varying‐coefficient hazard regression with application to breast cancer dose‐intensity data
Authors: Yin Guosheng , Li Hui 
Published: September 2009

AbstractTo enhance modeling flexibility, the authors propose a nonparametric hazard regression model, for which the ordinary and weighted least squares estimation and inference procedures are studied. The proposed model does not assume any parametric specifications on the covariate effects, which is suitable for exploring the nonlinear interactions between covariates, time and some exposure variable. The authors propose the local ordinary and weighted least squares estimators for the varying‐coefficient functions and establish the corresponding asymptotic normality properties. Simulation studies are conducted to empirically examine the finite‐sample performance of the new methods, and a real data example from a recent breast cancer study is used as an illustration. The Canadian Journal of Statistics 37: 659–674; 2009 © 2009 Statistical Society of Canada
Bayesian optimal design for changepoint problems
Authors: Atherton Juli , Charbonneau Benoit , Wolfson David B. , Joseph Lawrence , Zhou Xiaojie , Vandal Alain C. 
Published: September 2009

AbstractWe investigate Bayesian optimal designs for changepoint problems. We find robust optimal designs which allow for arbitrary distributions before and after the change, arbitrary prior densities on the parameters before and after the change, and any log‐concave prior density on the changepoint. We define a new design measure for Bayesian optimal design problems as a means of finding the optimal design. Our results apply to any design criterion function concave in the design measure. We illustrate our results by finding the optimal design in a problem motivated by a previous clinical trial. The Canadian Journal of Statistics 37: 495–513; 2009 © 2009 Statistical Society of Canada
Combined Pharmacophore Modeling, Docking, and 3D QSAR Studies of ABCB1 and ABCC1 Transporter Inhibitors
Authors: Pajeva Ilza K. , Globisch Christoph , Wiese Michael 
Published: September 2009

AbstractQuinazolinones, indolo‐ and pyrrolopyrimidines with inhibitory effects toward ABCB1 (P‐gp) and ABCC1 (MRP1) transporters were studied by pharmacophore modeling, docking, and 3D QSAR to describe the binding preferences of the proteins. The pharmacophore overlays between dual and/or highly selective inhibitors point to binding sites of different topology and physiochemical properties for MRP1 and P‐gp. Docking of selective inhibitors into the P‐gp binding cavity by the use of a structural model based on the recently resolved P‐gp structure confirms the P‐gp pharmacophore features identified, and reveals the interactions of some functional groups and atoms in the structures with particular protein residues. The 3D QSAR analysis of the dual‐effect inhibitors allows satisfactory prediction of the selectivity index of the compounds and outlines electrostatics as most important for selectivity. The results from the combined modeling approach complement each other and could improve our understanding of the protein–ligand interactions involved, and could aid in the development of highly selective and potent inhibitors of P‐gp and MRP1.
Towards virtualized desktop environment
Authors: Liao Xiaofei , Jin Hai , Hu Liting , Liu Haikun 
Published: September 2009

AbstractVirtualization is being widely used now as an emerging trend. Rapid improvements in network bandwidth, ubiquitous security hazards and high total cost of ownership of personal computers have created a growing market for desktop virtualization. Much like server virtualization, virtualizing desktops involves separating the physical location of a client device from its logical interface. But, the performance and usability of some traditional desktop frameworks do not satisfy end‐users. Other solutions, including WebOS, which needs to rebuild all daily‐used applications into Client/Server mode, cannot be easily accepted by people in a short time. We present LVD, a system that combines the virtualization technology and inexpensive personal computers (PCs) to realize a lightweight virtual desktop system. Comparing to the previous desktop systems, LVD builds an integrated novel desktop environment, which can support the backup, mobility, suspending and resuming of per‐user's working environment, and support synchronous using of incompatible applications on different platforms and achieves great saving in power consumption. We have implemented LVD in a cluster with Xen and compared its performance against widely used commercial approaches, including Microsoft RDP, Citrix MetaFrameXP and Sun Ray. Experimental results demonstrate that LVD is effective in performing the functions while imposing little overhead. Copyright © 2009 John Wiley & Sons, Ltd.
Thiamine and benfotiamine prevent apoptosis induced by high glucose‐conditioned extracellular matrix in human retinal pericytes
Authors: Beltramo Elena , Nizheradze Konstantin , Berrone Elena , Tarallo Sonia , Porta Massimo 
Published: September 2009

AbstractBackgroundEarly and selective loss of pericytes and thickening of the basement membrane are hallmarks of diabetic retinopathy. We reported reduced adhesion, but no changes in apoptosis, of bovine retinal pericytes cultured on extracellular matrix (ECM) produced by endothelial cells in high glucose (HG). Since human and bovine pericytes may behave differently in conditions mimicking the diabetic milieu, we verified the behaviour of human retinal pericytes cultured on HG‐conditioned ECM.MethodsPericytes were cultured in physiological/HG on ECM produced by human umbilical vein endothelial cells in physiological/HG, alone or in the presence of thiamine and benfotiamine. Adhesion, proliferation, apoptosis, p53 and Bcl‐2/Bax ratio (mRNA levels and protein concentrations) were measured in wild‐type and immortalized human pericytes.ResultsBoth types of pericytes adhered less to HG‐conditioned ECM and plastic than to physiological glucose‐conditioned ECM. DNA synthesis was impaired in pericytes cultured in HG on the three different surfaces but there were no differences in proliferation. DNA fragmentation and Bcl‐2/Bax ratio were greatly enhanced by HG‐conditioned ECM in pericytes kept in both physiological and HG. Addition of thiamine and benfotiamine to HG during ECM production completely prevented these damaging effects.ConclusionsApoptosis is strongly increased in pericytes cultured on ECM produced by endothelium in HG, probably due to impairment of the Bcl‐2/Bax ratio. Thiamine and benfotiamine completely revert this effect. This behaviour is therefore completely different from that of bovine pericytes, underlining the importance of establishing species‐specific cell models to study the mechanisms of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd.
Blood pressure levels in pre‐diabetic stages are associated with worse cognitive functioning in patients with type 2 diabetes
Authors: van den Berg Esther , Dekker Jacqueline M , Nijpels Giel , Kessels Roy P. C. , Kappelle L. Jaap , de Haan Edward H. F. , Heine Robert J. , Stehouwer Coen D. A. , Biessels Geert Jan 
Published: September 2009

AbstractBackgroundType 2 diabetes mellitus (T2DM) is associated with mild decrements in cognitive functioning, but the relation of these decrements to metabolic and vascular risk factors is unclear. The present study compared the vascular risk factor profile over the preceding 16 years between T2DM patients with good cognitive functioning and those with poor cognitive functioning.MethodsThe Hoorn study is a population‐based cohort study on glucose metabolism and vascular disease initiated in 1989, with follow‐up examinations in 1996–1998, 2000–2001 and 2005–2007. Cognitive functioning was assessed in 2005–2007. Patients who developed T2DM between 1989 and 2000–2001 (n = 64) were divided in tertiles (lowest tertile = ‘poor cognition’, highest tertile = ‘good cognition’) according to a sum score for performance across cognitive domains (SUM) and the domain score for information‐processing speed (IPS). The time course of vascular risk factors from 1989 to 2005–2007 was compared between these tertiles with linear mixed models adjusted for age, sex and estimated IQ.ResultsPresent levels (2005–2007) of vascular risk factors did not differ between patients with relatively poor or good cognition. However, patients with poor cognition had a 14–18 mmHg higher systolic blood pressure in 1989 than patients with good cognition. There were no differences in lipid profile and body weight at any time during the study between the groups. For IPS the T2DM patients with poor cognition even had a lower baseline HbA1c level than patients with good cognition.ConclusionsCognitive dysfunction in T2DM is related to the cumulative effects of long‐term exposure to hypertension, even in pre‐DM stages. Copyright © 2009 John Wiley & Sons, Ltd.
Comparison of insulin autoantibody: polyethylene glycol and micro‐IAA 1‐day and 7‐day assays
Authors: Babaya Naru , Yu Liping , Miao Dongmei , Wang Jian , Rewers Marian , Nakayama Maki , Liu Edwin , Barker Jennifer M. , Eisenbarth George S. 
Published: September 2009

AbstractBackgroundOlder studies of diabetes development typically utilized a 7‐day incubation polyethylene glycol competitive insulin autoantibody assay (CIAA). Our standard micro‐IAA assay (mIAA) utilizes precipitation with proteins A/G and 1‐day incubation (1‐day mIAA), but is less sensitive compared to the CIAA assay.MethodsWe performed CIAA and mIAA assays in various conditions. We analyzed serum samples from 446 type 1 diabetes patients, from another set of 247 type 1 diabetes patients within 2 weeks of initiation of insulin treatment, from 150 healthy control donors, from 22 healthy participants in the diabetes autoimmunity study in the young (DAISY), and also coded sera from 50 patients with newly diagnosed type 1 diabetes and 50 blood donor control samples.ResultsIn the process of our study, we found that the key condition was the incubation time. Therefore, we extended the incubation time to 7 days (7‐day mIAA assay). No CIAA‐negative control was positive with either 1‐day or 7‐day mIAA. In a new onset type 1 diabetes and at risk cohorts (DAISY study), the 7‐day mIAA identified an additional 18% as being positive along with 16% of those who were initially 1‐day mIAA negative and CIAA positive. Most subjects detectable only with the 7‐day mIAA assay had intermediate levels of CIAA (80–300 nU/mL) (p = 0.01).ConclusionsThe 7‐day mIAA assay identifies a small but significant additional subset of individuals positive on the CIAA assay, while preserving specificity. Copyright © 2009 John Wiley & Sons, Ltd.
Novel CD8+ Treg suppress EAE by TGF‐β‐ and IFN‐γ‐dependent mechanisms
Authors: Chen Mei‐Ling , Yan Bo‐Shiun , Kozoriz Deneen , Weiner Howard L. 
Published: September 2009

AbstractAlthough CD8+ Treg‐mediated suppression has been described, CD8+ Treg remain poorly characterized. Here we identify a novel subset of CD8+ Treg that express latency‐associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP− counterparts. In addition to TGF‐β, CD8+LAP+ cells produce IFN‐γ, and these cells suppress EAE that is dependent on both TGF‐β and IFN‐γ. In an adoptive co‐transfer model, CD8+LAP+ cells suppress myelin oligodendrocyte glycoprotein (MOG)‐specific immune responses by inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN‐γ production in vivo. Furthermore, in vivo neutralization of IFN‐γ and studies with IFN‐γ‐deficient mice demonstrate an important role for IFN‐γ production in the function of CD8+LAP+ cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8+ T cells and suggest that induction or amplification of CD8+LAP+ cells may be a therapeutic strategy to help control autoimmune processes.