bluuebunny/crossref_metadata_2025 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

A 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

Ultra‐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

Modeling 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

This 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

The 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

A 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

Six 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

Di‐ 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

To 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

We 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

Quinazolinones, 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

Virtualization 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

Background

Early 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.

Methods

Pericytes 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.

Results

Both 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.

Conclusions

Apoptosis 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

Background

Type 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.

Methods

The 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.

Results

Present 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.

Conclusions

Cognitive 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

Background

Older 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.

Methods

We 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.

Results

In 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).

Conclusions

The 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

Although 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.
Thymocyte deletion can bias Treg formation toward low‐abundance self‐peptide
Authors: Cozzo Picca Cristina , Oh Soyoung , Panarey Laura , Aitken Malinda , Basehoar Alissa , Caton Andrew J.
Published: September 2009

Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg as they develop intrathymically, but how these alternative developmental fates are specified based on interactions with self‐peptide(s) is not understood. We show here that thymocytes expressing an autoreactive TCR can be subjected to varying degrees of deletion that correlate with the amount of self‐peptide. Strikingly, among thymocytes that evade deletion, similar proportions acquire Foxp3 expression. These findings provide evidence that Foxp3+ Treg can develop among members of a cohort of autoreactive thymocytes that have evaded deletion by a self‐peptide, and that deletion and Treg formation can act together to bias the Treg repertoire toward low‐abundance self‐peptide(s).
First Synthesis of meso‐Chlorinated Tetrabenzoporphyrins
Authors: Ito Satoshi , Phong Le Thanh , Komatsu Takuya , Igarashi Nagisa , Otsubo Saika , Sakai Yoshimasa , Ohno Akira , Aramaki Shinji , Tanaka Yousuke , Uno Hidemitsu , Oba Toru , Hiratani Kazuhisa
Published: September 2009

meso‐Chlorinated bicyclo[2.2.2]octadiene‐fused porphyrins 2 (ClnTBCODPs; n = 1–4) have been synthesized by chlorination of the free base TBCODP‐H2 (1‐H2) using N‐chlorosuccinimide (NCS). The chlorinated derivatives were easily separated by column chromatography on silica gel to give 2‐H2 in good yields. This method for the chlorination of porphyrin using NCS is mild, safe, and economic compared with the established procedure for the meso‐chlorination of porphyrins. We also discovered the unexpected meso‐chlorination of the porphyrin with dichlorodicyanobenzoquinone (DDQ) by single‐electron transfer. ClnTBCODPs 2 were converted into tetrabenzoporphyrins (ClnTBPs) 3 in 100 % yields by retro‐Diels–Alder reaction. The derived compounds were characterized by NMR spectroscopy, UV/Vis spectrophotometry, cyclic voltammetry (CV), X‐ray crystallography, and organic field‐effect transistor (OFET) characteristics. The introduction of chlorine at the meso positions of the TBPs drastically changed their electronic and structural properties. The maxima of protonated Cl4TBP‐H2 (3d‐H2; λmax = 494, 649, and 707 nm) were redshifted by around 50–65 nm relative to those of protonated TBP‐H2 (λmax = 431, 605, and 660 nm). The two Q‐band maxima of the Cl4TBP dication are similar to those of a tetraacenaphthoporphyrin dication (λmax = 525, 646, and 702 nm), which has one of the most redshifted Q‐bands.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Prediction of spatially distributed seismic demands in specific structures: Structural response to loss estimation
Authors: Bradley Brendon A. , Dhakal Rajesh P. , MacRae Gregory A. , Cubrinovski Misko
Published: September 2009

A companion paper has investigated the effects of intensity measure (IM) selection in the prediction of spatially distributed response in a multi‐degree‐of‐freedom structure. This paper extends from structural response prediction to performance assessment metrics such as probability of structural collapse; probability of exceeding a specified level of demand or direct repair cost; and the distribution of direct repair loss for a given level of ground motion. In addition, a method is proposed to account for the effect of varying seismological properties of ground motions on seismic demand that does not require different ground motion records to be used for each intensity level. Results illustrate that the conventional IM, spectral displacement at the first mode, Sde(T1), produces higher risk estimates than alternative velocity‐based IM's, namely spectrum intensity, SI, and peak ground velocity, PGV, because of its high uncertainty in ground motion prediction and poor efficiency in predicting peak acceleration demands. Copyright © 2009 John Wiley & Sons, Ltd.
An experimental study on steel‐encased buckling‐restrained brace hysteretic dampers
Authors: Eryaşar Mehmet Emrah , Topkaya Cem
Published: September 2009

This paper describes a seismic test program performed on 12 steel‐encased buckling‐restrained braces (BRBs). The use of rolled or built‐up buckling‐restraining mechanisms with welded or bolted attachments was examined. In addition, the effects of bolt pretension, core‐to‐encasing attachment details, aspect ratio of core segment and imperfections due to manufacturing on the brace response were investigated. All specimens were subjected to a stepwise incremental quasi‐static testing protocol with a maximum axial strain amplitude of 2%. All specimens except one showed satisfactory performance with stable hysteretic response and sustained cumulative inelastic deformations in excess of 200 times the yield deformation. Based on the experimental results, the compression strength adjustment factor, and the strain hardening adjustment factor for each excursion were quantified. Test results revealed that these two factors are significantly influenced by the parameters investigated in the experimental program. BRB details were also found to influence the buckling and the yielding patterns of the core segment. Copyright © 2009 John Wiley & Sons, Ltd.
Prevalence and correlates of alcoholism in community‐dwelling elderly living in São Paulo, Brazil
Authors: Hirata Edson Shiguemi , Nakano Eduardo Yoshio , Junior Jony Arrais Pinto , Litvoc Júlio , Bottino Cássio M. C.
Published: September 2009

Objectives

To assess the prevalence of alcoholism in elderly living in the city of São Paulo (Brazil) and investigate associated risk factors.

Methods

A total of 1,563 individuals aged 60 years or older, of both genders of three districts of different socioeconomic classes (high, medium and low) in the city of São Paulo (Brazil) were interviewed. The CAGE screening test for alcoholism was applied and a structured interview was used to assess associated sociodemographic and clinical factors. The tests Mini Mental State Examination, Fuld Object Memory Evaluation, The Informant Questionnaire on Cognitive Decline in the Elderly and Bayer‐Activities of Daily Living Scale were used for cognitive and functional assessment.

Results

Prevalence of alcoholism was 9.1%. Multivariate regression analysis showed that alcoholism was associated with male gender, ‘mulatto’ ethnicity, smoking, and cognitive and functional impairment. In addition, the younger the individual and the lower the schooling level, the higher the risk for alcoholism.

Conclusions

The results obtained in this study show that alcoholism is highly frequent in the community‐dwelling elderly living in São Paulo, and that it is associated with socio‐demographic and clinical risk factors similar to those reported in the literature. This suggests that alcoholism in the elderly of a developing country shares the same basic characteristics seen in developed countries. These findings suggest that it is essential for health services and professional to be prepared to meet this demand that will significantly grow in the next years, especially in developing countries, where the rates of population aging are higher than those of developed countries. Copyright © 2009 John Wiley & Sons, Ltd.
Synthesis of the new types of N‐substituted aminomethylenebisorganophosphorus acids and their derivatives
Authors: Prishchenko Andrey A. , Livantsov Mikhail V. , Novikova Olga P. , Livantsova Ludmila I. , Petrosyan Valery S.
Published: September 2009

The interaction of esters of trivalent organophosphorus acids containing PH and POSiMe3 fragments with various derivatives of formamide is proposed as convenient methods for the synthesis of new N‐substituted aminomethylenebisorganophosphorus acids and their derivatives with three‐, four‐, and five‐coordinated phosphorus. Also the new functionalized derivatives of the new aminomethylenebisphosphinic acids with substituted hydroxymethyl moieties are synthesized, and some properties of the obtained compounds are presented. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:319–324, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20552
Dynamic change of T315I BCR‐ABL kinase domain mutation in Korean chronic myeloid leukaemia patients during treatment with Abl tyrosine kinase inhibitors
Authors: Kim Wan‐Seok , Kim Dongho , Kim Dong‐Wook , Kweon Il‐Young , Kim Soo‐Hyun , Goh Hyun‐Gyung , Park Sa‐Hee , Lee Jeong
Published: September 2009

We analysed the dynamic change of imatinib‐resistant mutations in BCR‐ABL kinase domain focusing on T315I mutation during dasatinib or nilotinib therapy. Fifty‐five imatinib‐resistant chronic myeloid leukaemia patients (32 patients with imatinib‐resistant mutations and 23 patients without mutation) in different disease phases were treated with dasatinib (median 17.3 months) or nilotinib (median 6.8 months). Among the 32 patients with baseline mutation, mutations including M244V, G250E, E255K, M351T, H396R, S417Y, E450K and E459K disappeared in 8 patients and new mutations were detected in 9 patients, all of which were T315I. Among the 23 patients without baseline mutation, 4 patients showed newly developed mutations including T315I, T315I + E459K, M244V and F359V. The T315I was the most frequently detected mutation in imatinib therapy (16%, 9 of 55) as well as in dasatinib or nilotinib therapy (24%, 11 of 44). Patients with imatinib resistant baseline mutations had a higher rate of mutation development during dasatinib or nilotinib treatment compared to patients without baseline mutations (28% vs. 17%). Copyright © 2009 John Wiley & Sons, Ltd.
Accountability, accreditation, and continuous improvement: Building a culture of evidence
Authors: Morest Vanessa Smith
Published: September 2009

Using mixed methods, building evaluation into new programs, and conducting research that is authentic and meaningful to the internal campus community can generate interest and help fuel a data‐intensive cultural transformation.
Taking a broader view: Using institutional research's natural qualities for transformation
Authors: Leimer Christina
Published: September 2009

By more widely applying its natural characteristics, institutional research can help foster a broad organizational view among campus constituents, connect people and ideas, facilitate collaboration, and stimulate organizational learning that leads to cultural transformation.
Quantified characterization of human cutaneous normal scar using multiphoton microscopy
Authors: Zhu Xiaoqin , Zhuo Shuangmu , Zheng Liqin , Lu Kecheng , Jiang Xingshan , Chen Jianxin , Lin Bifang
Published: September 2009

The morphological alterations of human cutaneous normal scar were quantitatively analyzed using multiphoton microscopy (MPM) based on two‐photon excited fluorescence and second harmonic generation. High‐contrast, high‐resolution images of normal scar and uninjured skin were obtained for comparison. In addition, some quantitative parameters have been extracted to quantitatively discriminate between normal scar and uninjured skin. The MPM combined with quantitative method enable a better understanding of microstructual alterations of the epidermis, elastic fiber, and collagen in normal scar. It may lead the way to making know the mechanism of normal scar formation and identifying feasible therapeutic options. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Nerve regeneration following spinal cord injury using matrix metalloproteinase‐sensitive, hyaluronic acid‐based biomimetic hydrogel scaffold containing brain‐derived neurotrophic factor
Authors: Park Jonghyuck , Lim Eunjeong , Back Seungkeun , Na Heungsik , Park Yongdoo , Sun Kyung
Published: September 2009

Spinal cord injury leads to the permanent loss of motor and sensory function in the body. To enhance spinal cord regeneration, we used a hyaluronic acid‐based hydrogel as a three‐dimensional biomimetic scaffold for peptides and growth factors. Three components were used to provide guidance cues: a matrix metalloproteinase peptide crosslinker, an IKVAV (Ile‐ Lys‐Val‐Ala‐Val) peptide derived from laminin, and brain‐derived neurotrophic factor (BDNF). Human mesenchymal stem cells (hMSCs) were cultured in hydrogels in vitro for 10 days to induce neuronal differentiation of hMSCs. Based on gene‐expression data, the matrix metalloproteinase‐sensitive peptide, IKVAV peptide, and BDNF were critical in the differentiation of hMSCs. Remodeling activity was found to be a key factor in guiding neural differentiation of stem cells. To test this approach in vivo, we used the spinal cord injured rat model and five different hydrogel compositions. Samples were injected into the intrathecal space, and animals were monitored for 6 weeks. Compared to all other groups, animals injected with BDNF‐containing hydrogels showed the greatest improvement on locomotive tests (Basso–Beattie–Bresnahan score) during the initial stage after injury. These results suggest that hyaluronic acid‐based hydrogels containing IKVAV and BDNF create microenvironments that foster differentiation of stem cells along the neural cell lineage, and they could be used to facilitate nerve regeneration after spinal cord injury. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
In vitro evaluation of the bioactive factors preserved in porcine small intestinal submucosa through cellular biological approaches
Authors: Yang Bin , Zhou Liuhua , Sun Zeyu , Yang Rong , Chen Yun , Dai Yutian
Published: September 2009

The objective of this study was to develop cellular biological approaches to evaluate the potential effect of bioactive factors in porcine small intestinal submucosa (SIS) on bladder regeneration and angiogenesis. For this purpose, we cultured human bladder smooth muscle cell (HBSMC) and human umbilical vein endothelial cell (HUVEC), and then used cellular biological techniques to characterize in vitro biological effect of SIS components on HBSMC and HUVEC. Our results indicated that the SIS components had stimulated the attachment, proliferation, and migration of HBSMC and HUVEC, as well as tube formation by HUVEC on Matrigel. These results implied that the SIS might have preserved a mixture of bioactive factors including cell adhesion factors, mitogenic factors, chemotactic cytokines, and angiogenic factors, and these bioactive factors would have the potential of promoting bladder regeneration and angiogenesis. In conclusion, these cellular biological approaches might be helpful and effective for evaluation of the bioactive factors preserved in porcine SIS before it is used for bladder augmentation in humans. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Effects of cell concentration and collagen concentration on contraction kinetics and mechanical properties in a bone marrow stromal cell‐collagen construct
Authors: Chieh Hsiao‐Feng , Sun Yulong , Liao Jiunn‐Der , Su Fong‐Chin , Zhao Chunfeng , Amadio Peter C. , An Kai‐Nan
Published: September 2009

A cell‐collagen construct is commonly used to investigate the phenomenon of wound healing and to estimate the variables for tissue engineering. The purpose of this study was to assess the effects of cell concentration and collagen concentration on the contraction kinetics and mechanical properties of bone marrow stromal cell (BMSC) seeded collagen lattices. To investigate the effects of both variables on the contraction kinetics, the construct contraction was monitored up to 13 days. Incremental stress– relaxation tests were carried out after a 2‐week incubation to obtain the stress–strain profiles, which were subsequently assessed in a quasilinear viscoelastic (QLV) model. During contraction, aligned BMSCs were observed first in the interior portion of the ring, followed by the middle portion and finally in the exterior portion. Constructs seeded with a higher initial cell concentration (higher than 1 × 105 cells/mL) or lower initial collagen concentration (lower than 2 mg/mL) exhibited faster contraction, higher ultimate stress, and superior elasticity and reduced relaxation behavior (p < 0.05). The cell‐collagen model was successfully used to yield information regarding the initial cell concentration and the initial collagen concentration on contraction kinetics and mechanical behavior, which may have possible application in tissue engineering. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
The topographical effect of electrospun nanofibrous scaffolds on the in vivo and in vitro foreign body reaction
Authors: Cao Haoqing , Mchugh Kevin , Chew Sing Yian , Anderson James M.
Published: September 2009

Topographical cues play an important role in influencing cellular behavior and are considered as significant parameters to be controlled in tissue engineering applications. This work investigated the biocompatibility with regard to scaffold architecture and topographical effect of nanofibrous scaffolds on the in vivo and in vitro foreign body reaction. Random and aligned polycaprolactone (PCL) nanofibers were fabricated by electrospinning technique, with diameters of 313 ± 5 nm and 506 ± 24 nm, respectively. Primary monocytes isolated from five human donors were cultured on PCL nanofibers, PCL film, and RGD‐coated glass in vitro and cell density and morphology was evaluated at time points of day 0 (2 h), day 3, day 7, and day 10. The in vivo study was carried out by implanting PCL nanofibers and film scaffolds subcutaneously in rats to test the biocompatibility and host response at time points of week 1, week 2, and week 4. The in vitro studies revealed that the initial monocyte adhesion on the aligned fiber scaffold was significantly less (p < 0.001) when compared to the random fiber scaffold. The in vivo study showed that the thicknesses of fibrous capsule on fibrous scaffolds were 7.55 ± 0.54 μm for aligned fibers and 4.13 ± 0.31 μm for random fibers, which were significantly thinner than that of film implants 37.7 ± 0.25 μm (p < 0.001). Additionally, cell infiltration was observed in aligned fibrous scaffolds both in vitro and in vivo, while on random fibers and films, distinct fibrous capsule boundaries were found on the surfaces. These results indicate that aligned electrospun nanofibers may serve as a promising scaffold for tissue engineering by minimizing host response, enhancing tissue‐scaffold integration, and eliciting a thinner fibrous capsule. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Artificial cartilage made from a novel double‐network hydrogel: In vivo effects on the normal cartilage and ex vivo evaluation of the friction property
Authors: Arakaki Kazunobu , Kitamura Nobuto , Fujiki Hiroyuki , Kurokawa Takayuki , Iwamoto Mikio , Ueno Masaru , Kanaya Fuminori , Osada Yoshihito , Gong Jian Ping , Yasuda Kazunori
Published: September 2009

This study evaluated the in vivo influence of a poly‐(2‐Acrylamido‐2‐methylpropane sulfonic acid)/poly‐(N,N'‐dimetyl acrylamide) (PAMPS/PDMAAm) double‐network (DN) hydrogel on counterface cartilage in rabbit knee joints and its ex vivo friction properties on normal cartilage. In the first experiment, the DN gel was implanted in a surgically created defect in the femoral trochlea of rabbit knee joints and the left knee was used as the control. Evaluations using a confocal laser scanning microscopy demonstrated that the DN gel did not affect the surface microstructure (surface roughness, the number of small pits) of the counterface cartilage in vivo at 4 and 12 weeks. The histology also showed that the DN gel hadno pathological damage on the cartilage matrices and cells at 4 weeks. However, two of the five DN gel‐implanted knees showed mild irregularity on the counterface cartilage surface at 12 weeks. In the second experiment, the friction property between the normal and the artificial cartilage was determined using a joint simulator apparatus. The ex vivo mean friction coefficient of the DN gel to normal cartilage was 0.029, while that of the normal‐to‐normal cartilage articulation was 0.188. The coefficient of the DN gel‐to‐normal cartilage articulation was significantly lower than that of the normal‐to‐normal cartilage articulation (p < 0.0001). This study suggested that the PAMPS/PDMAAm DN gel has very low friction coefficient on normal cartilage and has no significant detrimental effects on counterface cartilage in vivo, and can be a promising material to develop the artificial cartilage. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Myosin heavy chain composition of tiger (Panthera tigris) and cheetah (Acinonyx jubatus) hindlimb muscles
Authors: Hyatt Jon‐Philippe K. , Roy Roland R. , Rugg Stuart , Talmadge Robert J.
Published: September 2009

Felids have a wide range of locomotor activity patterns and maximal running speeds, including the very fast cheetah (Acinonyx jubatas), the roaming tiger (Panthera tigris), and the relatively sedentary domestic cat (Felis catus). As previous studies have suggested a relationship between the amount and type of activity and the myosin heavy chain (MHC) isoform composition of a muscle, we assessed the MHC isoform composition of selected hindlimb muscles from these three felid species with differing activity regimens. Using gel electrophoresis, western blotting, histochemistry, and immunohistochemistry with MHC isoform‐specific antibodies, we compared the MHC composition in the tibialis anterior, medial gastrocnemius (MG), plantaris (Plt), and soleus muscles of the tiger, cheetah, and domestic cat. The soleus muscle was absent in the cheetah. At least one slow (type I) and three fast (types IIa, IIx, and IIb) MHC isoforms were present in the muscles of each felid. The tiger had a high combined percentage of the characteristically slower isoforms (MHCs I and IIa) in the MG (62%) and the Plt (86%), whereas these percentages were relatively low in the MG (44%) and Plt (55%) of the cheetah. In general, the MHC isoform characteristics of the hindlimb muscles matched the daily activity patterns of these felids: the tiger has daily demands for covering long distances, whereas the cheetah has requirements for speed and power. J. Exp. Zool. 313A:45–57, 2010. © 2009 Wiley‐Liss, Inc.
Notch signaling: Key role in intrauterine infection/inflammation, embryonic development, and white matter damage?
Authors: Yuan Tian‐Ming , Yu Hui‐Min
Published: September 2009

The mechanisms or pathophysiologies that lead to cerebral white matter damage during development are complex and not fully understood. It is postulated that exposure of the preterm brain to inflammatory cytokines during intrauterine infection/inflammation contributes to brain white matter damage, and this damage may affect the function and differentiation of progenitor oligodendrocyte cells under physiological conditions. The Notch pathway, an important signaling pathway controlling various cells' differentiation, functions in the timing of oligodendrocyte differentiation, and Notch signaling may contribute to white matter damage and may mediate neurogenesis in a pathophysiological phase. Recent studies have led to recognition of the role of the Notch pathway in neurogenesis in cerebral ischemic damage and in myelination and axonal damage of neurodegenerative diseases. Moreover, Notch plays a critical role in steering an immune response toward inflammation by regulating expression of various cytokines and proinflammatory cytokines resulting in the activation of Notch signaling. Thus, the Notch signaling pathway likely plays a key role in intrauterine infection/inflammation, brain development, and white matter damage, and future research directed toward understanding its role will be important. Insofar as Notch signaling could have an important effect on neurogenesis, mobilization of progenitor cells is one strategy for compensating for the neuronal losses seen in white matter damage after intrauterine infection/inflammation. © 2009 Wiley‐Liss, Inc.